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Bahadoran Z, Mirmiran P, Ghasemi A, Azizi F. Excessive exposure to nitrate and nitrite boosts progression of isolated impaired fasting glucose to type 2 diabetes: a cohort study. J Diabetes Metab Disord 2025; 24:8. [PMID: 39697867 PMCID: PMC11649602 DOI: 10.1007/s40200-024-01517-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Accepted: 11/08/2024] [Indexed: 12/20/2024]
Abstract
Objectives This cohort study investigated the possible association of dietary nitrate (NO3)/nitrite (NO2) intake and risk of progression to type 2 diabetes (T2D) across different phenotypes of prediabetes (Pre-DM). Methods A total of 1586 adults diagnosed with Pre-DM [i.e., 60.2% isolated impaired fasting glucose (iIFG), 21% isolated impaired glucose tolerance (iIGT), and 18.8% combined IFG-IGT] in the third (2006-2008) and fourth (2009-2011) examinations of the Tehran Lipid and Glucose Study, were assessed for dietary intake of NO3 and NO2 and were followed up to 2015-2017. Cox proportional hazard models, stratified by Pre-DM phenotypes, were used to plot cumulative hazard curve and calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for developing T2D across tertile categories and per every 100 mg/d NO3 and 2 mg/d NO2 intake exceeded the acceptable daily intake (ADI). Results The mean age of the participants was 47.2 ± 12.9 years at baseline, and 52.2% were men. Highest intake of NO3 (≥ 645 vs. < 451 mg/d) and NO2 (≥ 11.5 vs. <9.0 mg/d) increased risk of T2D among subjects with iIFG (HR = 1.69, 95% CI = 1.04-2.74 and HR = 2.07, 95% CI = 1.29-3.32). The cumulative hazards were higher in the highest compared to the lowest NO3 and NO2 intake in subjects with iIFG phenotype. Every 100 mg/d of NO3 and 2 mg/d NO2 intake exceeded ADI was associated with an increased risk of progression from iIFG to T2D by 13 and 25%, respectively. Conclusion High exposure to dietary NO3 and NO2 may be a risk factor for developing T2D in subjects with iIFG.
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Affiliation(s)
- Zahra Bahadoran
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Micronutrient Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Parvin Mirmiran
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Asghar Ghasemi
- Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- No. 24, Sahid-Erabi St, Yemen St, Chamran Exp, P.O.Box: 19395-4763, Tehran, Iran
| | - Fereidoun Azizi
- Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Luo S, Wu X, Wang H, Zhang Y, Xie L. Nitrate induced hepatic fibrosis in tadpoles of Bufo gargarizans by mediating alterations in toll-like receptor signaling pathways. ENVIRONMENTAL RESEARCH 2025; 270:120961. [PMID: 39875068 DOI: 10.1016/j.envres.2025.120961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 01/22/2025] [Accepted: 01/25/2025] [Indexed: 01/30/2025]
Abstract
The nitrate pollution has become an increasingly serious environmental problem worldwide, and the toxic effects of elevated nitrate levels in the environment on aquatic animals remain to be elucidated. The purpose of the present study was to investigate the mechanisms of liver injury to tadpoles after exposure to nitrate from embryonic to metamorphic climax and to assess the recovery process of liver function after cessation of exposure. In the group with continuous nitrate exposure, the livers and thyroid of tadpoles showed remarkably histological lesions, of this with structural disorganization of the hepatocytes, cellular atrophy, and fibrosis, as well as significant reduction in the follicular and colloidal area of the thyroid. Meanwhile, the expression levels of genes related to inflammatory signaling pathways, such as TLR2, TLR6 and NF-κB, were significant elevated. After termination of exposure at Gs23, liver damage (histologic, ultrastructural, and molecular levels) was almost completely recovered, whereas thyroid gland damage was irreversible. Overall, this study shed light on the harmful effects of nitrate pollution on amphibian health and emphasizes the importance of controlling nitrate emissions in the environment.
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Affiliation(s)
- Shuangyan Luo
- College of Life and Environmental Science, Wenzhou University, 325003, Wenzhou, China; College of Life Science, Shaanxi Normal University, 710119, Xi'an, China
| | - Xueyi Wu
- College of Life and Environmental Science, Wenzhou University, 325003, Wenzhou, China
| | - Hongyuan Wang
- College of Life Science, Shaanxi Normal University, 710119, Xi'an, China
| | - Yongpu Zhang
- College of Life and Environmental Science, Wenzhou University, 325003, Wenzhou, China; Zhejiang Provincial Key Laboratory for Subtropical Water Environment and Marine Biological Resources Protection, Wenzhou University, 325003, Wenzhou, China.
| | - Lei Xie
- College of Life and Environmental Science, Wenzhou University, 325003, Wenzhou, China; Zhejiang Provincial Key Laboratory for Subtropical Water Environment and Marine Biological Resources Protection, Wenzhou University, 325003, Wenzhou, China.
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Sanchez-Orozco NY, Rosier BT, Ruiz-Gutierrez A, Marquez-Sandoval F, Artacho A, Carrera-Quintanar L, Mira A. The blood pressure lowering effect of beetroot juice is impaired in periodontitis and recovered after periodontal treatment. NPJ Biofilms Microbiomes 2025; 11:10. [PMID: 39788958 PMCID: PMC11717912 DOI: 10.1038/s41522-024-00622-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Accepted: 11/26/2024] [Indexed: 01/12/2025] Open
Abstract
We have previously demonstrated that subgingival levels of nitrate-reducing bacteria, as well as the in vitro salivary nitrate reduction capacity (NRC), were diminished in periodontitis patients, increasing after periodontal treatment. However, it remains unclear if an impaired NRC in periodontitis can affect systemic health. To determine this, the effect of nitrate-rich beetroot juice (BRJ) on blood pressure was determined in 15 periodontitis patients before and 70 days after periodontal treatment (i.e., professional mechanical plaque removal, oral hygiene instruction, and subgingival instrumentation), as well as in a healthy control group of 15 individuals. Additionally, subgingival and tongue samples were taken to analyse the bacterial composition with Illumina sequencing of the 16S rRNA gene. In healthy individuals, the systolic and diastolic blood pressure (SBP and DPB) decreased significantly (both P < 0.01) 90 min after BRJ intake, but not in periodontitis patients. However, after periodontal treatment, this blood pressure-lowering effect was recovered (P < 0.05 for SBP; P < 0.01 for DBP). Lower levels of salivary nitrate after identical doses of BRJ intake indicated a potentially higher NRC in healthy individuals (P < 0.05). Periodontitis-associated bacteria decreased in tongue and subgingival samples after periodontal treatment (P < 0.01). In contrast, nitrate-reducing bacteria were associated with health in both habitats, but increased only in subgingival plaque after periodontal treatment (P < 0.001). This is the first study showing that periodontitis could limit the blood-pressure lowering effects of nitrate reduction by the oral microbiota. We propose that an impaired NRC represents a potential link between periodontitis and systemic conditions, which should be confirmed in future randomized controlled trials. Future work should also aim to determine if nitrate prebiotic supplementation and/or tongue cleaning could improve the treatment of periodontitis and its associated comorbidities.
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Affiliation(s)
- Nydia Y Sanchez-Orozco
- PhD Program in Translational Nutrition Sciences, Department of Human Reproduction, Child Growth and Development, University Center of Health Sciences (CUCS), University of Guadalajara (UdeG), Guadalajara, Jalisco, Mexico
| | - Bob T Rosier
- Department of Health and Genomics, FISABIO Foundation, Valencia, Spain.
| | - Alondra Ruiz-Gutierrez
- Specialty of Periodontics, Department of Integral Dental Clinics, University Center of Health Sciences (CUCS), University of Guadalajara (UdeG), Guadalajara, Jalisco, Mexico
| | - Fabiola Marquez-Sandoval
- PhD Program in Translational Nutrition Sciences, Department of Human Reproduction, Child Growth and Development, University Center of Health Sciences (CUCS), University of Guadalajara (UdeG), Guadalajara, Jalisco, Mexico
| | - Alejandro Artacho
- Department of Health and Genomics, FISABIO Foundation, Valencia, Spain
| | - Lucrecia Carrera-Quintanar
- PhD Program in Translational Nutrition Sciences, Department of Human Reproduction, Child Growth and Development, University Center of Health Sciences (CUCS), University of Guadalajara (UdeG), Guadalajara, Jalisco, Mexico.
| | - Alex Mira
- Department of Health and Genomics, FISABIO Foundation, Valencia, Spain
- CIBER Center for Epidemiology and Public Health (CIBER-ESP), Madrid, Spain
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Gaydarski L, Petrova K, Angushev I, Stanchev S, Iliev A, Stamenov N, Kirkov V, Landzhov B. Exploring the Molecular Modalities in the Pathogenesis of Diabetic Kidney Disease with a Focus on the Potential Therapeutic Implications. Biomedicines 2024; 13:50. [PMID: 39857634 PMCID: PMC11763324 DOI: 10.3390/biomedicines13010050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Revised: 12/13/2024] [Accepted: 12/24/2024] [Indexed: 01/27/2025] Open
Abstract
Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease (CKD) and end-stage renal disease worldwide, affecting approximately 40% of individuals with type 2 diabetes (T2DM) and 30% of those with type 1 diabetes (T1DM). As the prevalence of diabetes continues to rise, the burden of DKD is expected to grow correspondingly. This review explores the roles of key molecular pathways, including the apelinergic system, vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) axis, and nitric oxide (NO)/nitric oxide synthase (NOS) signaling, in DKD pathogenesis and potential therapeutic applications. The apelinergic system, involving apelin and its receptor (APLNR), influences endothelial function, glucose metabolism, and renal health. Preclinical studies highlight its dual role in renal protection and injury through anti-inflammatory and antioxidant pathways, while other evidence suggests that it may exacerbate DKD through podocyte damage and angiogenesis. Similarly, the VEGF/VEGFR axis demonstrates a complex contribution to DKD, where VEGF-A promotes pathological angiogenesis and glomerular damage, but its inhibition requires careful modulation to prevent adverse effects. The NO/NOS system, integral to vascular and renal homeostasis, also exhibits altered activity in DKD, with reduced bioavailability linked to oxidative stress and inflammation. This review underscores the intricate interplay between these pathways in DKD, revealing both challenges and opportunities in their therapeutic targeting. Further research is essential to refine strategies and develop effective interventions for DKD management.
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Affiliation(s)
- Lyubomir Gaydarski
- Department of Anatomy, Histology and Embryology, Medical University of Sofia, 1431 Sofia, Bulgaria; (K.P.); (I.A.); (S.S.); (A.I.); (N.S.); (B.L.)
| | - Kristina Petrova
- Department of Anatomy, Histology and Embryology, Medical University of Sofia, 1431 Sofia, Bulgaria; (K.P.); (I.A.); (S.S.); (A.I.); (N.S.); (B.L.)
| | - Ivan Angushev
- Department of Anatomy, Histology and Embryology, Medical University of Sofia, 1431 Sofia, Bulgaria; (K.P.); (I.A.); (S.S.); (A.I.); (N.S.); (B.L.)
| | - Stancho Stanchev
- Department of Anatomy, Histology and Embryology, Medical University of Sofia, 1431 Sofia, Bulgaria; (K.P.); (I.A.); (S.S.); (A.I.); (N.S.); (B.L.)
| | - Alexandar Iliev
- Department of Anatomy, Histology and Embryology, Medical University of Sofia, 1431 Sofia, Bulgaria; (K.P.); (I.A.); (S.S.); (A.I.); (N.S.); (B.L.)
| | - Nikola Stamenov
- Department of Anatomy, Histology and Embryology, Medical University of Sofia, 1431 Sofia, Bulgaria; (K.P.); (I.A.); (S.S.); (A.I.); (N.S.); (B.L.)
| | - Vidin Kirkov
- Department of Health Policy and Management, Faculty of Public Health ‘Prof. Dr. Tzekomir Vodenicharov’, Medical University of Sofia, 1527 Sofia, Bulgaria;
| | - Boycho Landzhov
- Department of Anatomy, Histology and Embryology, Medical University of Sofia, 1431 Sofia, Bulgaria; (K.P.); (I.A.); (S.S.); (A.I.); (N.S.); (B.L.)
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Fernandes-Costa F, Gomes da Silva RT, de Almeida AJPO, de Medeiros IA, de Assis Tafuri LS, Dos Santos GJ, Carlstrom M, Cruz JC. Organic vs. inorganic nitrates: Metabolic and vascular outcomes in STZ-induced diabetes in mice. Life Sci 2024; 359:123257. [PMID: 39561873 DOI: 10.1016/j.lfs.2024.123257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 11/09/2024] [Accepted: 11/15/2024] [Indexed: 11/21/2024]
Abstract
BACKGROUND Diabetic animals often display dysregulated nitric oxide (NO) metabolism, contributing to vascular dysfunction. This study evaluates the metabolic and vascular effects of organic nitrate isosorbide mononitrate (ISMN) versus inorganic sodium nitrate (NaNO3) in mice with type 1 diabetes mellitus (T1DM) induced by streptozotocin (STZ). EXPERIMENTAL APPROACH T1DM was induced in male C57Bl6 mice with STZ ip and confirmed by fasting glucose. Mice were treated with ISMN (10 mg·kg-1) or NaNO3 (85 mg·L-1) for 14 days. A combination of in vivo, in vitro, and ex vivo studies assessed cardiometabolic benefits. RESULTS Both nitrates reduced blood and urinary hyperglycemia in T1DM mice, with ISMN exhibiting more significant reductions in blood glucose. ISMN and NaNO3 similarly reduced water and food intake, urinary volume, glucose intolerance, and insulin resistance while increasing insulin and nitrite levels in serum and urine. Both nitrates improved endothelium-independent vascular function and attenuated reactive oxygen species (ROS) while increasing NO levels in the aortic rings of T1DM mice. Furthermore, both nitrates similarly reduced mean arterial pressure in T1DM mice. CONCLUSION AND IMPLICATIONS ISMN and NaNO₃ have demonstrated comparable hypotensive and antioxidant effects, offering metabolic and vascular benefits in STZ-TDM1 mice. The more pronounced reduction in blood glucose with ISMN treatment compared to NaNO₃ is particularly promising. The antihyperglycemic effects of both nitrates were linked to increased serum insulin levels and enhanced insulin sensitivity. These results provide a foundation for future clinical studies to evaluate the potential of ISMN or NaNO3 as antidiabetogenic and antihypertensive adjuvant therapies in diabetic patients.
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Affiliation(s)
- Francineide Fernandes-Costa
- Graduate Program in Bioactive Synthetic and Natural Products, Center for Health Sciences, Federal University of Paraíba, João Pessoa, Brazil
| | | | | | - Isac Almeida de Medeiros
- Department of Pharmaceutical Sciences, Health Sciences Center, Federal University of Paraíba, João Pessoa, Brazil
| | | | - Gustavo Jorge Dos Santos
- Multicenter Graduate Program in Physiological Sciences, Department of Physiological Sciences, Center for Biological Sciences, Federal University of Santa Catarina - UFSC, Brazil
| | - Mattias Carlstrom
- Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
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Tegegne BA, Adugna A, Yenet A, Yihunie Belay W, Yibeltal Y, Dagne A, Hibstu Teffera Z, Amare GA, Abebaw D, Tewabe H, Abebe RB, Zeleke TK. A critical review on diabetes mellitus type 1 and type 2 management approaches: from lifestyle modification to current and novel targets and therapeutic agents. Front Endocrinol (Lausanne) 2024; 15:1440456. [PMID: 39493778 PMCID: PMC11527681 DOI: 10.3389/fendo.2024.1440456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 10/02/2024] [Indexed: 11/05/2024] Open
Abstract
Diabetes mellitus (DM) has emerged as an international health epidemic due to its rapid rise in prevalence. Consequently, scientists and or researchers will continue to find novel, safe, effective, and affordable anti-diabetic medications. The goal of this review is to provide a thorough overview of the role that lifestyle changes play in managing diabetes, as well as the standard medications that are currently being used to treat the condition and the most recent advancements in the development of novel medical treatments that may be used as future interventions for the disease. A literature search was conducted using research databases such as PubMed, Web of Science, Scopus, ScienceDirect, Wiley Online Library, Google Scholar, etc. Data were then abstracted from these publications using words or Phrases like "pathophysiology of diabetes", "Signe and symptoms of diabetes", "types of diabetes", "major risk factors and complication of diabetes", "diagnosis of diabetes", "lifestyle modification for diabetes", "current antidiabetic agents", and "novel drugs and targets for diabetes management" that were published in English and had a strong scientific foundation. Special emphasis was given to the importance of lifestyle modification, as well as current, novel, and emerging/promising drugs and targets helpful for the management of both T1DM and T2DM.
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Affiliation(s)
- Bantayehu Addis Tegegne
- Department of Pharmacy, College of Medicine and Health Science, Debre Markos University, Debre Markos, Ethiopia
| | - Adane Adugna
- Department of Medical Laboratory Science, College of Medicine and Health Science, Debre Markos University, Debre Markos, Ethiopia
| | - Aderaw Yenet
- Department of Pharmacy, College of Medicine and Health Science, Debre Markos University, Debre Markos, Ethiopia
| | - Wubetu Yihunie Belay
- Department of Pharmacy, College of Medicine and Health Science, Debre Markos University, Debre Markos, Ethiopia
| | - Yared Yibeltal
- Department of Pharmacy, College of Medicine and Health Science, Debre Markos University, Debre Markos, Ethiopia
| | - Abebe Dagne
- Department of Pharmacy, College of Medicine and Health Science, Debre Markos University, Debre Markos, Ethiopia
| | - Zigale Hibstu Teffera
- Department of Medical Laboratory Science, College of Medicine and Health Science, Debre Markos University, Debre Markos, Ethiopia
| | - Gashaw Azanaw Amare
- Department of Medical Laboratory Science, College of Medicine and Health Science, Debre Markos University, Debre Markos, Ethiopia
| | - Desalegn Abebaw
- Department of Medical Laboratory Science, College of Medicine and Health Science, Debre Markos University, Debre Markos, Ethiopia
| | - Haymanot Tewabe
- Department of Medical Laboratory Science, College of Medicine and Health Science, Debre Markos University, Debre Markos, Ethiopia
| | - Rahel Belete Abebe
- Department of Clinical Pharmacy, School of Pharmacy, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia
| | - Tirsit Ketsela Zeleke
- Department of Pharmacy, College of Medicine and Health Science, Debre Markos University, Debre Markos, Ethiopia
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Darabi Z, Siervo M, Webb RJ, McMahon N, Ghayour-Mobarhan M, Khayyatzadeh SS, Mazidi M. Dietary nitrate intake and association with markers of cardiometabolic risk in Iranian female adolescents. Eur J Clin Nutr 2024; 78:264-269. [PMID: 38212504 DOI: 10.1038/s41430-023-01378-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Revised: 10/31/2023] [Accepted: 11/27/2023] [Indexed: 01/13/2024]
Abstract
Dietary nitrates are thought to confer several cardiometabolic health benefits, including improvements in blood pressure and the plasma lipid profile. However, existing data from Iran is conflicting and there is a dearth of literature focusing on non-adult populations. A total of 988 adolescent girls were recruited from schools in different areas of Mashhad and Sabzevar, Iran. Dietary nitrate intake was assessed using a food frequency questionnaire and participants were categorized into quartiles based on this. Differences in participant characteristics between quartiles were assessed using one-way ANOVA and associations between total nitrate intake, nitrate intake from vegetables and cardiometabolic risk markers (blood lipid profile, fasting blood glucose, systolic and diastolic blood pressure) were assessed using linear regression. Nitrate intake from vegetables was positively correlated with triglycerides, even after adjusting for several variables (β = 0.086, 95% CI = 0.002-0.097; P = 0.043). Total nitrate intake was also significantly positively associated with serum triglycerides (β = 0.097, 95% CI = 0.010-0.084; P = 0.012); however, this relationship disappeared after adjusting for several variables. Significant interaction effects were observed between total nitrate intake, nitrate intake from vegetables, and vitamin C upon triglycerides (P < 0.01). No significant relationships were found between total nitrate intake, nitrate intake from vegetables, and other cardiometabolic risk markers. Our findings suggest there may be neutral or possibly detrimental cardiovascular effects of dietary nitrate and/or vitamin C intake which are not in agreement with contemporary literature and warrant further investigation.
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Affiliation(s)
- Zahra Darabi
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Research Center for Food Hygiene and Safety, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Mario Siervo
- School of Life Sciences, Division of Physiology, Pharmacology and Neuroscience, University of Nottingham, Queen's Medical Centre, Nottingham, UK
- Curtin Dementia Centre of Excellence, EnAble Institute, Curtin University, Kent Street, Bentley, WA, 6102, Australia
| | - Richard J Webb
- School of Health and Sport Sciences, Hope Park Campus, Liverpool Hope University, Taggart Avenue, Liverpool, L16 9JD, UK
| | - Nicholas McMahon
- School of Human Movement and Nutrition Sciences, University of Queensland, St. Lucia, QLD, Australia
| | - Majid Ghayour-Mobarhan
- International UNESCO Center for Health Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sayyed Saeid Khayyatzadeh
- Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
- Research Center for Food Hygiene and Safety, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
| | - Mohsen Mazidi
- Department of Twin Research, King's College London, London, UK
- Medical Research Council Population Health Research Unit, University of Oxford, Oxford, UK
- Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK
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Chen D, Parks CG, Beane Freeman LE, Hofmann JN, Sinha R, Madrigal JM, Ward MH, Sandler DP. Ingested nitrate and nitrite and end-stage renal disease in licensed pesticide applicators and spouses in the Agricultural Health Study. JOURNAL OF EXPOSURE SCIENCE & ENVIRONMENTAL EPIDEMIOLOGY 2024; 34:322-332. [PMID: 38191926 PMCID: PMC11142909 DOI: 10.1038/s41370-023-00625-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Revised: 11/22/2023] [Accepted: 11/28/2023] [Indexed: 01/10/2024]
Abstract
BACKGROUND Nitrate and nitrite ingestion has been linked to kidney cancer, possibly via the endogenous formation of carcinogenic N-nitroso compounds. These exposures might also contribute to end-stage renal disease (ESRD). OBJECTIVES We investigated associations of drinking water nitrate and dietary nitrate and nitrite intakes (total and by food type) with incident ESRD in the Agricultural Health Study. We also explored modifying effects of vitamin C and heme iron intake, which may affect endogenous nitrosation. METHODS We performed complete case analyses among private pesticide applicators and their spouses. We obtained water nitrate estimates for participants whose primary drinking water source at enrollment (1993-1997) was public water supplies (PWS) or private wells (N = 59,632). Average nitrate concentrations were computed from historical data for PWS users and predicted from random forest models for private well users. Analysis of dietary nitrate and nitrite was restricted to the 30,177 participants who completed the NCI Dietary History Questionnaire during follow-up (1999-2003). Incident ESRD through 2018 was ascertained through linkage with the U.S. Renal Data System. We estimated adjusted hazard ratios (HRs) and 95%CI for associations of tertiles (T) of exposure with ESRD overall and explored effects in strata of vitamin C and heme iron intake. RESULTS We identified 469 incident ESRD cases (206 for dietary analysis). Water nitrate and total dietary nitrate/nitrite were not associated with ESRD, but increased ESRD was associated with nitrate and nitrite from processed meats. We found apparent associations between nitrite and ESRD only among participants with vitamin C SIGNIFICANCE ESRD incidence was associated with dietary nitrate/nitrite from processed meat among all study participants and with total dietary nitrite among participants with lower vitamin C or higher heme iron intake. IMPACT STATEMENT There are few well-established environmental risk factors for end-stage renal disease (ESRD), a worldwide public health challenge. Ingestion of nitrate and nitrite, which may lead to endogenous formation of carcinogenic N-nitroso compounds, has been linked to some cancers and chronic diseases. We investigated these exposures in relation to ESRD in an agricultural cohort. ESRD incidence was associated with dietary nitrate/nitrite from processed meat and with total dietary nitrite among subgroups with lower vitamin C or higher heme iron intake. This study provides preliminary evidence that points to dietary nitrite and possibly dietary nitrate intake as a potential contributor to ESRD.
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Affiliation(s)
- Dazhe Chen
- Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA
| | - Christine G Parks
- Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA
| | - Laura E Beane Freeman
- Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA
| | - Jonathan N Hofmann
- Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA
| | - Rashmi Sinha
- Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA
| | - Jessica M Madrigal
- Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA
| | - Mary H Ward
- Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Rockville, MD, USA
| | - Dale P Sandler
- Epidemiology Branch, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, USA.
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9
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Bahadoran Z, Mirmiran P, Azizi F, Ghasemi A. Systemic nitric oxide metabolites and the chance of pre-diabetes regression to normoglycemia: A 9-year cohort study. BIOIMPACTS : BI 2024; 14:29917. [PMID: 39296799 PMCID: PMC11406430 DOI: 10.34172/bi.2024.29917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Revised: 12/10/2023] [Accepted: 01/02/2024] [Indexed: 09/21/2024]
Abstract
Introduction We aimed to track longitudinal changes of glycemic status in subjects with pre-diabetes (Pre-DM) in relation to their baseline levels of systemic nitric oxide (NO) production [i.e., measured as serum NO metabolites (NOx), crude and body weight (BW)-adjusted NOx to creatinine ratio (NOx-to-Cr)] over 9 years. Methods This cohort study included 541 middle-aged Iranian men and women with Pre-DM, recruited in 2006-2008 and followed up to 2015-2017. The colorimetric Griess method was used to measure serum NOx concentration. Multinomial logistic regression analyses estimated the odds ratios (OR) of Pre-DM regression and progression across tertiles (tertile 3 vs. tertile 1 and tertile 2) of serum NOx, crude, and BW-adjusted NOx-to-Cr ratio. Results Participants who regressed to normoglycemia (NG) had a higher BW-adjusted NOx-to-Cr ratio than those who developed type 2 diabetes (T2D) or those who remained Pre-DM (0.52±0.34 vs. 0.43±0.25 and 0.48±0.29, P=0.023). Higher BW-adjusted NOx-to-Cr increased chance of returning to NG (OR=2.05, 95% CI= 0.98-4.32, P=0.058) and decreased levels of 2h-serum glucose over time (P time×group=0.025), as well as the decreased overall mean of fasting (106, 95% CI=103-109 vs. 110, 95% CI=108-112 mg/dL, P=0.008) and 2h-serum glucose (153, 95% CI=146-159 vs. 163, 95% CI=158-168 mg/dL, P=0.018). Conclusion A higher endogenous NO production (i.e., indirectly measured by BW- and Cr-adjusted serum NOx concentration) in Pre-DM subjects is associated with the chance of returning to NG.
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Affiliation(s)
- Zahra Bahadoran
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Parvin Mirmiran
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fereidoun Azizi
- Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Asghar Ghasemi
- Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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10
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Rosier BT, Johnston W, Carda-Diéguez M, Simpson A, Cabello-Yeves E, Piela K, Reilly R, Artacho A, Easton C, Burleigh M, Culshaw S, Mira A. Nitrate reduction capacity of the oral microbiota is impaired in periodontitis: potential implications for systemic nitric oxide availability. Int J Oral Sci 2024; 16:1. [PMID: 38177101 PMCID: PMC10767001 DOI: 10.1038/s41368-023-00266-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Revised: 11/13/2023] [Accepted: 12/05/2023] [Indexed: 01/06/2024] Open
Abstract
The reduction of nitrate to nitrite by the oral microbiota has been proposed to be important for oral health and results in nitric oxide formation that can improve cardiometabolic conditions. Studies of bacterial composition in subgingival plaque suggest that nitrate-reducing bacteria are associated with periodontal health, but the impact of periodontitis on nitrate-reducing capacity (NRC) and, therefore, nitric oxide availability has not been evaluated. The current study aimed to evaluate how periodontitis affects the NRC of the oral microbiota. First, 16S rRNA sequencing data from five different countries were analyzed, revealing that nitrate-reducing bacteria were significantly lower in subgingival plaque of periodontitis patients compared with healthy individuals (P < 0.05 in all five datasets with n = 20-82 samples per dataset). Secondly, subgingival plaque, saliva, and plasma samples were obtained from 42 periodontitis patients before and after periodontal treatment. The oral NRC was determined in vitro by incubating saliva with 8 mmol/L nitrate (a concentration found in saliva after nitrate-rich vegetable intake) and compared with the NRC of 15 healthy individuals. Salivary NRC was found to be diminished in periodontal patients before treatment (P < 0.05) but recovered to healthy levels 90 days post-treatment. Additionally, the subgingival levels of nitrate-reducing bacteria increased after treatment and correlated negatively with periodontitis-associated bacteria (P < 0.01). No significant effect of periodontal treatment on the baseline saliva and plasma nitrate and nitrite levels was found, indicating that differences in the NRC may only be revealed after nitrate intake. Our results suggest that an impaired NRC in periodontitis could limit dietary nitrate-derived nitric oxide levels, and the effect on systemic health should be explored in future studies.
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Affiliation(s)
- Bob T Rosier
- Department of Genomics and Health, FISABIO Foundation, Center for Advanced Research in Public Health, Valencia, Spain
| | - William Johnston
- Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Glasgow, UK
- Oral Sciences, University of Glasgow Dental School, School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
| | - Miguel Carda-Diéguez
- Department of Genomics and Health, FISABIO Foundation, Center for Advanced Research in Public Health, Valencia, Spain
| | - Annabel Simpson
- Sport and Physical Activity Research Institute, University of the West of Scotland, Blantyre, Scotland
| | - Elena Cabello-Yeves
- Department of Genomics and Health, FISABIO Foundation, Center for Advanced Research in Public Health, Valencia, Spain
- Instituto de Biomedicina de Valencia, Consejo Superior de Investigaciones Científicas (IBV-CSIC), Valencia, Spain
| | - Krystyna Piela
- Oral Sciences, University of Glasgow Dental School, School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
| | - Robert Reilly
- Oral Sciences, University of Glasgow Dental School, School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
| | - Alejandro Artacho
- Department of Genomics and Health, FISABIO Foundation, Center for Advanced Research in Public Health, Valencia, Spain
| | - Chris Easton
- Sport and Physical Activity Research Institute, University of the West of Scotland, Blantyre, Scotland
| | - Mia Burleigh
- Sport and Physical Activity Research Institute, University of the West of Scotland, Blantyre, Scotland
| | - Shauna Culshaw
- Oral Sciences, University of Glasgow Dental School, School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
| | - Alex Mira
- Department of Genomics and Health, FISABIO Foundation, Center for Advanced Research in Public Health, Valencia, Spain.
- CIBER Center for Epidemiology and Public Health, Madrid, Spain.
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11
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Liu H, Huang Y, Huang M, Wang M, Ming Y, Chen W, Chen Y, Tang Z, Jia B. From nitrate to NO: potential effects of nitrate-reducing bacteria on systemic health and disease. Eur J Med Res 2023; 28:425. [PMID: 37821966 PMCID: PMC10566198 DOI: 10.1186/s40001-023-01413-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Accepted: 09/29/2023] [Indexed: 10/13/2023] Open
Abstract
Current research has described improving multisystem disease and organ function through dietary nitrate (DN) supplementation. They have provided some evidence that these floras with nitrate (NO3-) reductase are mediators of the underlying mechanism. Symbiotic bacteria with nitrate reductase activity (NRA) are found in the human digestive tract, including the mouth, esophagus and gastrointestinal tract (GT). Nitrate in food can be converted to nitrite under the tongue or in the stomach by these symbiotic bacteria. Then, nitrite is transformed to nitric oxide (NO) by non-enzymatic synthesis. NO is currently recognized as a potent bioactive agent with biological activities, such as vasodilation, regulation of cardiomyocyte function, neurotransmission, suppression of platelet agglutination, and prevention of vascular smooth muscle cell proliferation. NO also can be produced through the conventional L-arginine-NO synthase (L-NOS) pathway, whereas endogenous NO production by L-arginine is inhibited under hypoxia-ischemia or disease conditions. In contrast, exogenous NO3-/NO2-/NO activity is enhanced and becomes a practical supplemental pathway for NO in the body, playing an essential role in various physiological activities. Moreover, many diseases (such as metabolic or geriatric diseases) are primarily associated with disorders of endogenous NO synthesis, and NO generation from the exogenous NO3-/NO2-/NO route can partially alleviate the disease progression. The imbalance of NO in the body may be one of the potential mechanisms of disease development. Therefore, the impact of these floras with nitrate reductase on host systemic health through exogenous NO3-/NO2-/NO pathway production of NO or direct regulation of floras ecological balance is essential (e.g., regulation of body homeostasis, amelioration of diseases, etc.). This review summarizes the bacteria with nitrate reductase in humans, emphasizing the relationship between the metabolic processes of this microflora and host systemic health and disease. The potential effects of nitrate reduction bacteria on human health and disease were also highlighted in disease models from different human systems, including digestive, cardiovascular, endocrine, nervous, respiratory, and urinary systems, providing innovative ideas for future disease diagnosis and treatment based on nitrate reduction bacteria.
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Affiliation(s)
- Hongyu Liu
- Department of Oral Surgery, School of Stomatology, Southern Medical University, Guangzhou, China
| | - Yisheng Huang
- Department of Oral Surgery, School of Stomatology, Southern Medical University, Guangzhou, China
| | - Mingshu Huang
- Department of Oral Surgery, School of Stomatology, Southern Medical University, Guangzhou, China
| | - Min Wang
- Department of Oral Surgery, School of Stomatology, Southern Medical University, Guangzhou, China
| | - Yue Ming
- Department of Oral Surgery, School of Stomatology, Southern Medical University, Guangzhou, China
| | - Weixing Chen
- Department of Oral Surgery, School of Stomatology, Southern Medical University, Guangzhou, China
| | - Yuanxin Chen
- Department of Oral Surgery, School of Stomatology, Southern Medical University, Guangzhou, China
| | - Zhengming Tang
- Department of Oral Surgery, School of Stomatology, Southern Medical University, Guangzhou, China
| | - Bo Jia
- Department of Oral Surgery, School of Stomatology, Southern Medical University, Guangzhou, China.
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12
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Yousefzadeh N, Jeddi S, Zarkesh M, Kashfi K, Ghasemi A. Altered sialin mRNA gene expression in type 2 diabetic male Wistar rats: implications for nitric oxide deficiency. Sci Rep 2023; 13:4013. [PMID: 36899088 PMCID: PMC10006425 DOI: 10.1038/s41598-023-31240-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Accepted: 03/08/2023] [Indexed: 03/12/2023] Open
Abstract
Nitrate therapy has been suggested to boost nitric oxide (NO) levels in type 2 diabetes (T2D); however, little is known about nitrate transport across the membranes. This study aimed to assess changes in the mRNA expression of sialin, as a nitrate transporter, in the main tissues of rats with T2D. Rats were divided into two groups (n = 6/group): Control and T2D. A high-fat diet combined with a low dose of streptozotocin (STZ, 30 mg/kg) was used to induce T2D. At month 6, samples from the main tissues of rats were used to measure the mRNA expression of sialin and levels of NO metabolites. Rats with T2D had lower nitrate levels in the soleus muscle (66%), lung (48%), kidney (43%), aorta (30%), adrenal gland (58%), epididymal adipose tissue (eAT) (61%), and heart (37%) and had lower nitrite levels in the pancreas (47%), kidney (42%), aorta (33%), liver (28%), eAT (34%), and heart (32%). The order of sialin gene expression in control rats was: soleus muscle > kidney > pancreas > lung > liver > adrenal gland > brain > eAT > intestine > stomach > aorta > heart. Compared to controls, rats with T2D had higher sialin mRNA expressions in the stomach (2.1), eAT (2.0), adrenal gland (1.7), liver (8.9), and soleus muscle (3.4), and lower sialin expression in the intestine (0.56), pancreas (0.42), and kidney (0.44), all P values < 0.05. These findings indicate altered sialin mRNA expression in the main tissues of male T2D rats and may have implications for future NO-based treatment of T2D.
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Affiliation(s)
- Nasibeh Yousefzadeh
- Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No. 24, Arabi Street, Daneshjoo Blvd, Velenjak, P.O. Box 19395-4763, Tehran, Iran
| | - Sajad Jeddi
- Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No. 24, Arabi Street, Daneshjoo Blvd, Velenjak, P.O. Box 19395-4763, Tehran, Iran
| | - Maryam Zarkesh
- Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Khosrow Kashfi
- Department of Molecular, Cellular, and Biomedical Sciences, Sophie Davis School of Biomedical Education, City University of New York School of Medicine, New York, NY, USA
| | - Asghar Ghasemi
- Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No. 24, Arabi Street, Daneshjoo Blvd, Velenjak, P.O. Box 19395-4763, Tehran, Iran.
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13
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Bagheripour F, Jeddi S, Kashfi K, Ghasemi A. Metabolic effects of L-citrulline in type 2 diabetes. Acta Physiol (Oxf) 2023; 237:e13937. [PMID: 36645144 DOI: 10.1111/apha.13937] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Revised: 01/01/2023] [Accepted: 01/10/2023] [Indexed: 01/17/2023]
Abstract
The prevalence of type 2 diabetes (T2D) is increasing worldwide. Decreased nitric oxide (NO) bioavailability is involved in the pathophysiology of T2D and its complications. L-citrulline (Cit), a precursor of NO production, has been suggested as a novel therapeutic agent for T2D. Available data from human and animal studies indicate that Cit supplementation in T2D increases circulating levels of Cit and L-arginine while decreasing circulating glucose and free fatty acids and improving dyslipidemia. The underlying mechanisms for these beneficial effects of Cit include increased insulin secretion from the pancreatic β cells, increased glucose uptake by the skeletal muscle, as well as increased lipolysis and β-oxidation, and decreased glyceroneogenesis in the adipose tissue. Thus, Cit has antihyperglycemic, antidyslipidemic, and antioxidant effects and has the potential to be used as a new therapeutic agent in the management of T2D. This review summarizes available literature from human and animal studies to explore the effects of Cit on metabolic parameters in T2D. It also discusses the possible mechanisms underlying Cit-induced improved metabolic parameters in T2D.
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Affiliation(s)
- Fatemeh Bagheripour
- Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sajad Jeddi
- Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Khosrow Kashfi
- Department of Molecular, Cellular and Biomedical Sciences, Sophie Davis School of Biomedical Education, City University of New York School of Medicine, New York, New York, USA
| | - Asghar Ghasemi
- Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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14
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Kosti RI, Tsiampalis T, Kouvari M, Chrysohoou C, Georgousopoulou E, Pitsavos CS, Panagiotakos DB. The association of specific types of vegetables consumption with 10-year type II diabetes risk: Findings from the ATTICA cohort study. J Hum Nutr Diet 2023; 36:226-240. [PMID: 35770418 DOI: 10.1111/jhn.13056] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Revised: 06/14/2022] [Accepted: 06/15/2022] [Indexed: 01/19/2023]
Abstract
BACKGROUND The present study aimed to investigate the association between vegetable consumption, in total as well as per type/category, and 10-year type-2 diabetes mellitus (T2DM) incidence. METHODS The ATTICA study was conducted during 2001-2012 in 3042 apparently healthy adults living in Athens area, Greece. A detailed biochemical, clinical, and lifestyle evaluation was performed; vegetable consumption (total, per type) was evaluated through a validated semi-quantitative food frequency questionnaire. After excluding those with no complete information of diabetes status or those lost at the 10-year follow-up, data from 1485 participants were used for the current analysis. RESULTS After adjusting for several participants' characteristics, including overall dietary habits, it was observed that participants consuming at least 4 servings/day of vegetables had a 0.42-times lower risk of developing T2DM (hazard ratio [HR] = 0.42; 95% confidence interval [CI] = 0.29-0.61); the benefits of consumption were greater in women (HR = 0.29; 95% CI = 0.16-0.53) compared to men (HR = 0.56; 95% CI = 0.34-0.92). Only 33% of the sample consumed vegetables 4 servings/day. The most significant associations were observed for allium vegetables in women and for red/orange/yellow vegetables, as well as for legumes in men. CONCLUSIONS The intake of at least 4 servings/day of vegetables was associated with a considerably reduced risk of T2DM, independently of other dietary habits; underlying the need for further elaboration of current dietary recommendations at the population level.
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Affiliation(s)
- Rena I Kosti
- Department of Nutrition and Dietetics, School of Physical Education, Sport Science and Dietetics, University of Thessaly, Trikala, Greece
| | - Thomas Tsiampalis
- Department of Nutrition and Dietetics, School of Health Sciences and Education, Harokopio University, Athens, Greece
| | - Matina Kouvari
- Department of Nutrition and Dietetics, School of Health Sciences and Education, Harokopio University, Athens, Greece.,First Cardiology Clinic, School of Medicine, University of Athens, Athens, Greece
| | - Christina Chrysohoou
- First Cardiology Clinic, School of Medicine, University of Athens, Athens, Greece
| | - Ekavi Georgousopoulou
- Department of Nutrition and Dietetics, School of Health Sciences and Education, Harokopio University, Athens, Greece.,School of Medicine, The University of Notre Dame, Sydney, NSW, Australia.,Medical School, Australian National University, Canberra, ACT, Australia
| | - Christos S Pitsavos
- First Cardiology Clinic, School of Medicine, University of Athens, Athens, Greece
| | - Demosthenes B Panagiotakos
- Department of Nutrition and Dietetics, School of Health Sciences and Education, Harokopio University, Athens, Greece.,Faculty of Health, University of Canberra, Canberra, ACT, Australia
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15
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Mirmiran P, Teymoori F, Farhadnejad H, Mokhtari E, Salehi-Sahlabadi A. Nitrate containing vegetables and dietary nitrate and nonalcoholic fatty liver disease: a case control study. Nutr J 2023; 22:3. [PMID: 36627671 PMCID: PMC9830756 DOI: 10.1186/s12937-023-00834-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Accepted: 12/29/2022] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Vegetables is the main sources of dietary nitrate. Studies suggested the potential link between nitrate content of vegetables and reduce the risk of chronic diseases. We aimed to assess the association between nitrate-containing vegetables (NCVs) with odds of nonalcoholic fatty liver diseases (NAFLD) in Iranian adults. METHOD This case-control study was performed on a total of 225 newly diagnosed NAFLD cases and 450 controls aged 20-60 years. Individuals' dietary intakes were determined using a valid and reliable food frequency questionnaire. RESULTS The mean ± SD age and BMI of participants were 38.1 ± 8.8 years and 26.8 ± 4.3 kg/m2, respectively. In the fully adjusted model, the odds of NAFLD were decreased across tertiles of total NCVs [(adjusted OR: 0.20, 95%CI: 0.10-0.40), (Ptrend < 0.001)] and low-nitrate vegetables [(adjusted OR: 0.22, 95%CI: 0.11-0.48), (Ptrend < 0.001)]. Our results showed that each one SD increments in nitrate content of vegetables (adjusted OR: 0.73, 95%CI: 0.55-0.97) and nitrate content of fruits (adjusted OR: 0.59, 95%CI: 0.36-0.97) was associated with reduced odds of NAFLD (P < 0.05). However, there was a positive association between each one SD increments in nitrate content of dairy products and meats and processed meats with odds of NAFLD (adjusted OR: 1.34, 95%CI: 1.03-1.74), (P < 0.05). CONCLUSION Our finding suggested that a higher intake of vegetable nitrate may be related to a decrease the odds of NAFLD.
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Affiliation(s)
- Parvin Mirmiran
- grid.411600.2Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Farshad Teymoori
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. .,Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran.
| | - Hossein Farhadnejad
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. .,Department of Clinical Nutrition and Dietetics, Facualty of Nutrition and Food Technology, National Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Ebrahim Mokhtari
- grid.411600.2Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ammar Salehi-Sahlabadi
- grid.411600.2Department of Clinical Nutrition and Dietetics, Facualty of Nutrition and Food Technology, National Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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16
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Jiang W, Zhang J, Yang R, Sun X, Wu H, Zhang J, Liu S, Sun C, Ma L, Han T, Wei W. Association of urinary nitrate with diabetes complication and disease-specific mortality among adults with hyperglycemia. J Clin Endocrinol Metab 2022; 108:1318-1329. [PMID: 36576885 DOI: 10.1210/clinem/dgac741] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Revised: 12/16/2022] [Accepted: 12/19/2022] [Indexed: 12/29/2022]
Abstract
BACKGROUND The hyperglycemia condition disrupts the metabolism of nitrate/nitrite and nitric oxide, and dietary nitrate intake can restore nitric oxide homeostasis. This study aims to examine whether urinary nitrate is associated with diabetes complications and long-term survival among people with hyperglycemia. METHODS A total of 6208 people with hyperglycemia who participated in the National Health and Nutrition Examination Survey from 2005 to 2014 were enrolled. Diabetes complications included congestive heart failure, coronary heart disease, angina, stroke, myocardial infarction, diabetic retinopathy, and nephropathy. Mortality wasobtained from the National Death Index until 2015. Urinary nitrate was measured by ion chromatography coupled with electrospray tandem mass spectrometry, which was log-transformed and categized into tertiles. Logistic regression models and cox proportional hazards models were respectively performed to assess the association of urinary nitrate with the risk of diabetes complications and disease-specific mortalities. RESULTS After adjustment for potential confounders including urinary perchlorate and thiocyanate, compared with the participants in the lowest tertile of nitrate, the participants in the highest tertile had lower risks of congestive heart failure(odd-ratio[OR] = 0.41, 95%CI:0.27-0.60) and diabetic nephropathy(OR = 0.50, 95%CI: 0.41-0.62). Meanwhile, during a total follow-up of 41,463 person-year, the participants in the highest tertile had lower mortality risk of all-cause(hazard-ratio[HR] = 0.78, 95%CI:0.62-0.97), cardiovascular disease(CVD)(HR = 0.56, 95%CI:0.37-0.84) and diabetes(HR = 0.47, 95%CI:0.24-0.90), which showed dose-dependent linear relationships(P for non-linearity > 0.05). Moreover, no association between nitrate and cancer mortality was observed(HR = 1.13, 95%CI:0.71-1.80). CONCLUSIONS Higher urinary nitrate is associated with lower risk of congestive heart failure and diabetic nephropathy, and lower risk of all-cause, CVD, and diabetes mortalities. These findings indicated that inorganic nitrate supplementation can be considered as a supplementary treatment for people with hyperglycemia.
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Affiliation(s)
- Wenbo Jiang
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, P. R.China
- Department of Cardiology, the First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Jia Zhang
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, P. R.China
| | - Ruiming Yang
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, P. R.China
| | - Xinyi Sun
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, P. R.China
| | - Huanyu Wu
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, P. R.China
| | - Jiacheng Zhang
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, P. R.China
| | - Siyao Liu
- Division of Epidemiology, Biostatistics and Environmental Health, School of Public Health, University of Memphis, Memphis, TN
| | - Changhao Sun
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, P. R.China
| | - Lifang Ma
- Department of Pharmacology, College of Pharmacy Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin Medical University, Harbin, P. R.China
| | - Tianshu Han
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, P. R.China
| | - Wei Wei
- Department of Nutrition and Food Hygiene, the National Key Discipline, School of Public Health, Harbin Medical University, Harbin, P. R.China
- Department of Geriatrics, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, P.R.China
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17
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Acute inorganic nitrate intake increases regional insulin action in the brain: Results of a double-blind, randomized, controlled cross-over trial with abdominally obese men. Neuroimage Clin 2022; 35:103115. [PMID: 35843050 PMCID: PMC9421446 DOI: 10.1016/j.nicl.2022.103115] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2022] [Revised: 06/28/2022] [Accepted: 07/10/2022] [Indexed: 01/01/2023]
Abstract
AIMS Improving brain insulin sensitivity may be a promising approach in the prevention and treatment of metabolic and cognitive diseases. Our aim was to investigate acute effects of inorganic nitrate on regional cerebral blood flow (CBF) responses to intranasal insulin in abdominally obese men. METHODS Eighteen apparently healthy men, aged 18-60 years and with a waist circumference ≥ 102 cm, participated in a randomized, double-blind, placebo-controlled cross-over trial. The study consisted of two test days separated by at least one week. Men received in random order a drink providing 10 mmol (i.e., 625 mg nitrate) potassium nitrate or an isomolar placebo drink with potassium chloride. Brain insulin action was assessed 120-150 min after the drinks by quantifying acute effects of nasal insulin on regional CBF using arterial spin labeling Magnetic Resonance Imaging. Glucose and insulin concentrations were measured at regular intervals, while blood pressure was determined fasted and at 240 min. RESULTS Inorganic nitrate intake increased regional insulin action in five brain clusters. The two largest clusters were located in the right temporal lobe (ΔCBF: 7.0 ± 3.8 mL/100 g/min, volume: 5296 mm3, P < 0.001; and ΔCBF: 6.5 ± 4.3 mL/100 g/min, volume: 3592 mm3, P < 0.001), while two other cortical clusters were part of the right frontal (ΔCBF: 9.0 ± 6.0 mL/100 g/min, volume: 1096 mm3, P = 0.007) and the left parietal lobe (ΔCBF: 6.1 ± 4.3 mL/100 g/min, volume: 1024 mm3, P = 0.012). One subcortical cluster was located in the striatum (ΔCBF: 5.9 ± 3.2 mL/100 g/min, volume: 1792 mm3, P < 0.001). No effects of nitrate were observed on CBF before administration. Following nitrate intake, circulating nitrate plus nitrite concentrations increased over time (P = 0.003), but insulin and glucose concentrations and blood pressure did not change. CONCLUSION Acute inorganic nitrate intake may improve regional brain insulin action in abdominally obese men. These regions are involved in the regulation of different metabolic and cognitive processes. The trial was registered on January 6th, 2021 at ClinicalTrials.gov as NCT04700241.
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18
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karimzadeh L, Sohrab G, Hedayati M, Ebrahimof S, Emami G, Razavion T. Effects of concentrated beetroot juice consumption on glycemic control, blood pressure, and lipid profile in type 2 diabetes patients: randomized clinical trial study. Ir J Med Sci 2022:10.1007/s11845-022-03090-y. [PMID: 35869311 PMCID: PMC9307292 DOI: 10.1007/s11845-022-03090-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2022] [Accepted: 06/30/2022] [Indexed: 11/28/2022]
Abstract
Background While the prevalence of type 2 diabetes (T2D) is growing worldwide, dietary intake plays a remarkable role in the management of disease complications. Evidence suggests that beetroot has health-promoting potentials, including anti-inflammatory, antioxidant, and antidiabetic properties. Therefore, the present clinical trial aimed to investigate the effects of concentrated beetroot juice (BJ) supplementation on anthropometric measures, glycemic control, blood pressure (BP), and lipid profile in T2D patients. Methods In the simply randomized, parallel-group, controlled, and open-label trial, forty-six patients with T2D were randomly allocated to either the intervention group (BJ group), who consumed 24 ml concentrated BJ daily for 12 weeks, or the control group without any intervention. Anthropometric measurements, physical activity, dietary intakes, glycemic measures, lipid profile, and blood pressure were assessed at the baseline and the end of the study. Results Plasma nitric oxide (NO) in the intervention group had a higher nonsignificant increase after 12 weeks compared with the control group (8.57 ± 23.93 vs. 2.31 ± 15.98, P = 0.128). Compared with the baseline, significant reductions in plasma insulin (14.55 ± 7.85 vs. 10.62 ± 6.96, P = 0.014) and homeostasis model assessment of β-cell function (HOMA-B) (3.96 ± 0.83 vs. 3.63 ± 0.75, P = 0.038), as well as a marginally significant reduction in high-density lipoprotein cholesterol (HDL-C) (70.81 ± 11.24 vs. 65.44 ± 6.46, P = 0.058) were observed in the control group after 12 weeks. Diastolic blood pressure (DBP) was significantly reduced in the BJ group compared with the baseline (74.73 ± 16.78 vs. 72.36 ± 16.09, P = 0.046). After adjusting for baseline values, no significant effect on the levels of fasting plasma glucose (FPG), insulin, hemoglobin A1c (HgA1c), HOMA-β, homeostatic model assessment for insulin resistance (HOMA-IR), total cholesterol (TC), low-density lipoprotein (LDL), HDL, triglycerides (TG), and blood pressure (BP) was observed. Conclusions Our study showed that daily consumption of 24 ml concentrated BJ did not affect the levels of glycemic measures, blood pressure, and lipid profile. More studies are necessary to confirm these findings. Trial Registration This present clinical trial has been registered in the Iranian Registry of Clinical Trials with registration number IRCT20150815023617N5.
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Affiliation(s)
- Laleh karimzadeh
- Clinical Nutrition and Dietetics Department, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Golbon Sohrab
- Clinical Nutrition and Dietetics Department, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mehdi Hedayati
- Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Samira Ebrahimof
- Department of Nutrition Research, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institutle, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Golpar Emami
- Health Deputy, Mazandaran University of Medical Sciences, Sari, Iran
| | - Taraneh Razavion
- Department of Medical Parasitology and Mycology of Public Health, Tehran University of Medical Sciences, Tehran, Iran
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Sayyar A, Oladi M, Hosseini M, Nakhaee S, Ataie Z, Farrokhfall K. Effect of red beetroot juice on oxidative status and islet insulin release in adult male rats. Diabetol Metab Syndr 2022; 14:58. [PMID: 35461298 PMCID: PMC9034606 DOI: 10.1186/s13098-022-00830-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2022] [Accepted: 04/06/2022] [Indexed: 11/10/2022] Open
Abstract
INTRODUCTION Beetroot is rich in inorganic nitrate and it has been shown that inorganic nitrate has beneficial effects on metabolic syndrome. This study aims to investigate the effect of red beetroot juice (RBJ) on carbohydrate metabolism in adult insulin-resistant rats. MATERIALS AND METHODS Sixteen male Wistar rats (32 weeks old) were divided into two equal groups: control and RBJ. Treatment with drinking water (control) and 100% RBJ (RBJ) was lasted for 5 weeks. At the end of the 4th week the intraperitoneal glucose tolerance test was performed and at the end of the study period animals were sacrificed and blood and tissue (aorta, heart, and liver) samples were collected. Furthermore, pancreatic islets were isolated and their insulin secretion activity was investigated in different glycemic conditions. RESULTS Compared to the control group, RBJ-treated rats showed lower blood glucose and insulin levels in the glucose tolerance test. Serum and tissue levels of nitric oxide in the RBJ group were significantly higher than those in the control group. The liver peroxidation and serum aspartate transaminase levels were significantly increased in the RBJ-treated animals compared to the control group. The islets of RBJ group exhibited lower insulin secretion, especially in 16.7 mM glucose concentration (supraphysiologic condition) than control group. CONCLUSIONS RBJ consumption improves glucose metabolism in rats via increasing nitric oxide metabolites in an insulin-independent manner. However, future studies are needed to minimize the potential hepatic adverse consequences.
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Affiliation(s)
- Armin Sayyar
- Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran
| | - Mohammad Oladi
- Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran
| | - Mehran Hosseini
- Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Samaneh Nakhaee
- Medical Toxicology and Drug Abuse Research Center (MTDRC), Birjand University of Medical Sciences, Birjand, Iran
| | - Zomorrod Ataie
- Health Clinical Science Research Center, Islamic Azad University, Zahedan Branch, Zahedan, Iran
- Student Research Committee, Islamic Azad University, Zahedan Branch, Zahedan, Iran
| | - Khadijeh Farrokhfall
- Experimental Medicine Laboratory, Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran.
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Nikolaidis A, Kramer R, Ostojic S. Nitric Oxide: The Missing Factor in COVID-19 Severity? Med Sci (Basel) 2021; 10:3. [PMID: 35076566 PMCID: PMC8788438 DOI: 10.3390/medsci10010003] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Revised: 12/13/2021] [Accepted: 12/14/2021] [Indexed: 11/17/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) is a contagious respiratory and vascular disease that continues to spread among people around the world, mutating into new strains with increased transmission rates, such as the delta variant. The scientific community is struggling to discover the link between negative COVID-19 outcomes in patients with preexisting conditions, as well as identify the cause of the negative clinical patient outcomes (patients who need medical attention, including hospitalization) in what seems like a widespread range of COVID-19 symptoms that manifest atypically to any preexisting respiratory tract infectious diseases known so far. Having successfully developed a nutritional formulation intervention based on nitrate, a nitric oxide precursor, the authors hypothesis is that both the comorbidities associated with negative clinical patient outcomes and symptoms associated with COVID-19 sickness are linked to the depletion of a simple molecule: nitric oxide.
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Affiliation(s)
| | - Ron Kramer
- ThermoLife International, Phoenix, AZ 85048, USA;
| | - Sergej Ostojic
- Applied Bioenergetics Lab, Faculty of Sport and PE, University of Novi Sad, 21102 Novi Sad, Serbia;
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21
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Bahadoran Z, Mirmiran P, Carlström M, Ghasemi A. Inorganic nitrate: A potential prebiotic for oral microbiota dysbiosis associated with type 2 diabetes. Nitric Oxide 2021; 116:38-46. [PMID: 34506950 DOI: 10.1016/j.niox.2021.09.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 07/07/2021] [Accepted: 09/05/2021] [Indexed: 11/29/2022]
Abstract
Oral microbiota dysbiosis, concomitant with decreased abundance of nitrate (NO3-)-reducing bacteria, oral net nitrite (NO2-) production, and reduced nitric oxide (·NO) bioactivity, is associated with the development of cardiometabolic disorders. Therefore, restoring the oral microbiome to a health-associated state is suggested as a therapeutic approach to potentiate the NO3--NO2--·NO pathway and provide a backup resource for insufficient NO production in conditions including cardiovascular disease and type 2 diabetes mellitus (T2DM). The current review discusses how inorganic NO3- can improve the oral microbial community in patients with T2DM and act as a prebiotic. Both animal and human experiments indicated that inorganic NO3- modulates the oral microbiome by increasing the abundance of health-associated NO3--reducing bacteria (e.g., Neisseria and Rothia) and decreasing the plenty of species Prevotella and Veillonella, leading to oral NO2- accumulation and improved systemic ·NO availability. Supplementation with NO3- reduces caries- and periodontitis-associated bacteria and the pathogenic genus related to insulin resistance and glucose intolerance. In addition, inorganic NO3- may provide a more optimal environment for NO3- reductase activity in the oral cavity, as it increases salivary flow rate and prevents decreased pH by inhibiting acid-producing bacteria.
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Affiliation(s)
- Zahra Bahadoran
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Parvin Mirmiran
- Department of Clinical Nutrition and Human Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mattias Carlström
- Department of Physiology and Pharmacology, Karolinska Institutet, Biomedicum 5B, Stockholm, SE-171 76, Sweden
| | - Asghar Ghasemi
- Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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22
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Moreira LDSG, Fanton S, Cardozo L, Borges NA, Combet E, Shiels PG, Stenvinkel P, Mafra D. Pink pressure: beetroot (Beta vulgaris rubra) as a possible novel medical therapy for chronic kidney disease. Nutr Rev 2021; 80:1041-1061. [PMID: 34613396 DOI: 10.1093/nutrit/nuab074] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Chronic kidney disease (CKD) manifests with systemic inflammation, oxidative stress, and gut dysbiosis, resulting in metabolic disorders and elevated rates of cardiovascular disease-associated death. These all correlate with a high economic cost to healthcare systems. Growing evidence indicates that diet is an indispensable ally in the prevention and management of CKD and its complications. In this context, the root vegetable beetroot (Beta vulgaris rubra) deserves special attention because it is a source of several bioactive compounds, such as nitrate, betaine, and betalain, and has shown beneficial effects in CKD, including reduction of blood pressure, anti-inflammatory effects, and antioxidant actions by scavenging radical oxidative species, as observed in preclinical studies. Beetroot consumption as a possible therapeutic strategy to improve the clinical treatment of patients with CKD and future directions for clinical studies are addressed in this narrative review.
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Affiliation(s)
- Laís de Souza Gouveia Moreira
- L.d.S.G. Moreira and D. Mafra are with the Graduate Program in Medical Sciences, Fluminense Federal University, Niterói, Rio de Janiero, Brazil. S. Fanton, L. Cardozo, and D. Mafra are with the Graduate Program in Cardiovascular Sciences, Federal Fluminense University, Niterói-Rio de Janeiro, RJ, Brazil. N.A. Borges is with the Institute of Nutrition, State University of Rio de Janeiro, Rio de Janeiro, Brazil. E. Combet is with the School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom. P.G. Shiels is with the Wolfson Wohl Translational Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom. P. Stenvinkel is with the Department of Renal Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Susane Fanton
- L.d.S.G. Moreira and D. Mafra are with the Graduate Program in Medical Sciences, Fluminense Federal University, Niterói, Rio de Janiero, Brazil. S. Fanton, L. Cardozo, and D. Mafra are with the Graduate Program in Cardiovascular Sciences, Federal Fluminense University, Niterói-Rio de Janeiro, RJ, Brazil. N.A. Borges is with the Institute of Nutrition, State University of Rio de Janeiro, Rio de Janeiro, Brazil. E. Combet is with the School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom. P.G. Shiels is with the Wolfson Wohl Translational Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom. P. Stenvinkel is with the Department of Renal Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Ludmila Cardozo
- L.d.S.G. Moreira and D. Mafra are with the Graduate Program in Medical Sciences, Fluminense Federal University, Niterói, Rio de Janiero, Brazil. S. Fanton, L. Cardozo, and D. Mafra are with the Graduate Program in Cardiovascular Sciences, Federal Fluminense University, Niterói-Rio de Janeiro, RJ, Brazil. N.A. Borges is with the Institute of Nutrition, State University of Rio de Janeiro, Rio de Janeiro, Brazil. E. Combet is with the School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom. P.G. Shiels is with the Wolfson Wohl Translational Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom. P. Stenvinkel is with the Department of Renal Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Natalia A Borges
- L.d.S.G. Moreira and D. Mafra are with the Graduate Program in Medical Sciences, Fluminense Federal University, Niterói, Rio de Janiero, Brazil. S. Fanton, L. Cardozo, and D. Mafra are with the Graduate Program in Cardiovascular Sciences, Federal Fluminense University, Niterói-Rio de Janeiro, RJ, Brazil. N.A. Borges is with the Institute of Nutrition, State University of Rio de Janeiro, Rio de Janeiro, Brazil. E. Combet is with the School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom. P.G. Shiels is with the Wolfson Wohl Translational Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom. P. Stenvinkel is with the Department of Renal Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Emilie Combet
- L.d.S.G. Moreira and D. Mafra are with the Graduate Program in Medical Sciences, Fluminense Federal University, Niterói, Rio de Janiero, Brazil. S. Fanton, L. Cardozo, and D. Mafra are with the Graduate Program in Cardiovascular Sciences, Federal Fluminense University, Niterói-Rio de Janeiro, RJ, Brazil. N.A. Borges is with the Institute of Nutrition, State University of Rio de Janeiro, Rio de Janeiro, Brazil. E. Combet is with the School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom. P.G. Shiels is with the Wolfson Wohl Translational Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom. P. Stenvinkel is with the Department of Renal Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Paul G Shiels
- L.d.S.G. Moreira and D. Mafra are with the Graduate Program in Medical Sciences, Fluminense Federal University, Niterói, Rio de Janiero, Brazil. S. Fanton, L. Cardozo, and D. Mafra are with the Graduate Program in Cardiovascular Sciences, Federal Fluminense University, Niterói-Rio de Janeiro, RJ, Brazil. N.A. Borges is with the Institute of Nutrition, State University of Rio de Janeiro, Rio de Janeiro, Brazil. E. Combet is with the School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom. P.G. Shiels is with the Wolfson Wohl Translational Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom. P. Stenvinkel is with the Department of Renal Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Peter Stenvinkel
- L.d.S.G. Moreira and D. Mafra are with the Graduate Program in Medical Sciences, Fluminense Federal University, Niterói, Rio de Janiero, Brazil. S. Fanton, L. Cardozo, and D. Mafra are with the Graduate Program in Cardiovascular Sciences, Federal Fluminense University, Niterói-Rio de Janeiro, RJ, Brazil. N.A. Borges is with the Institute of Nutrition, State University of Rio de Janeiro, Rio de Janeiro, Brazil. E. Combet is with the School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom. P.G. Shiels is with the Wolfson Wohl Translational Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom. P. Stenvinkel is with the Department of Renal Medicine, Karolinska University Hospital, Stockholm, Sweden
| | - Denise Mafra
- L.d.S.G. Moreira and D. Mafra are with the Graduate Program in Medical Sciences, Fluminense Federal University, Niterói, Rio de Janiero, Brazil. S. Fanton, L. Cardozo, and D. Mafra are with the Graduate Program in Cardiovascular Sciences, Federal Fluminense University, Niterói-Rio de Janeiro, RJ, Brazil. N.A. Borges is with the Institute of Nutrition, State University of Rio de Janeiro, Rio de Janeiro, Brazil. E. Combet is with the School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom. P.G. Shiels is with the Wolfson Wohl Translational Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom. P. Stenvinkel is with the Department of Renal Medicine, Karolinska University Hospital, Stockholm, Sweden
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Ghazisaeidi B, Sarvghadi F, Ghasemi A, Tohidi M, Azizi F, Amouzegar A. Association Between Serum Nitric Oxide Level and Changes in Thyroid Function Test in a Population-based Study: Tehran Thyroid Study Participants (TTS). Int J Endocrinol Metab 2021; 19:e109214. [PMID: 34567136 PMCID: PMC8453649 DOI: 10.5812/ijem.109214] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2020] [Revised: 12/20/2020] [Accepted: 01/18/2021] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Nitric oxide (NO) plays a key role in thyroid function regulation through the inhibition of iodide (I) uptake at the thyroidal sodium-iodide symporter (NIS) and impacts on the thyroid vascularity and blood flow. OBJECTIVES This study aimed to evaluate the association between serum NO metabolites (NOx) and thyroid-stimulating hormone (TSH), free thyroxin (FT4), and anti-thyroid peroxidase (TPOAb) changes. Also, it aimed at evaluating the correlation between serum NOx and the incidence of clinical hypothyroidism, characterized by elevated TSH level and decreased FT4 concentration, and subclinical hypothyroidism, characterized by mildly elevated TSH level despite FT4 concentration within the normal range, over three years of follow-up. METHODS This study included 1,137 participants of the Tehran Thyroid study (TTS), aged > 20 years old, for whom data on serum TSH, FT4, and TPOAb in the third and fourth phases, and serum NOx in the third phase were available. Changes in TSH (ΔTSH), FT4 (ΔFT4), and TPOAb (ΔTPO) between the third and fourth phases were calculated, and the associations between serum NOx and ΔTSH, ΔFT4, and ΔTPOAb were assessed after multivariable adjustment using linear regression analysis. RESULTS No significant association was found between serum NOx and ΔTSH, ΔFT4, and ΔTPOAb after the multivariable adjustment; neither was any observed in TPOAb split groups after multivariable adjustment. No significant association was found between serum NOx tertiles and clinical and subclinical hypothyroidism incidence in the fourth phase of TTS. CONCLUSIONS There was no association between serum NOx levels and changes in TSH, FT4, and TPOAb and clinical and subclinical hypothyroidism incidence.
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Affiliation(s)
- Behnaz Ghazisaeidi
- Endocrine Research Center, Research Institute for Endocrine Sciences, Ayatollah Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Farzaneh Sarvghadi
- School of Medicine, Ayatollah Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Asghar Ghasemi
- Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Tohidi
- Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fereidoun Azizi
- Endocrine Research Center, Research Institute for Endocrine Sciences, Ayatollah Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Atieh Amouzegar
- Endocrine Research Center, Research Institute for Endocrine Sciences, Ayatollah Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Corresponding Author: Endocrine Research Center, Research Institute for Endocrine Sciences, Ayatollah Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Bairagi U, Jacob J. Macroporous Polyzwitterionic Gels As Versatile Intermediates for the Fixation and Release of Anions. LANGMUIR : THE ACS JOURNAL OF SURFACES AND COLLOIDS 2021; 37:5424-5435. [PMID: 33891417 DOI: 10.1021/acs.langmuir.1c00888] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
A new stable and functional polyzwitterion poly[1-(carboxymethyl)-4-methacrylamidopyridin-1-ium] was synthesized. The zwitterionic polymer shows its isoelectric point at a pH of 4.2, bidirectional pH responsiveness, and formation of dendritic fractal self-aggregated structures. Using this as a common intermediate, a simple, direct, and scalable single-step protocol was established to introduce various elementary anions like NO3-, HSO4-, H2PO4-, F-, Cl-, Br-, I-, CH3COO-, and HCOO- in their salt forms by reaction with the corresponding acids. FESEM studies on cross-linked polymeric hydrogels established the macroporous nature of these materials with their pore size in the range of 10-15 μm. Bidirectional swelling behavior was observed in these hydrogels from gel swelling kinetics and pH studies. Anion release studies in deionized water and buffer solutions showed ∼82 and ∼95% cumulative release for nitrate and phosphate anions, respectively, in 72 h. Our studies suggest that multifunctional polyzwitterionic gels are promising intermediates in the fixation and release of anions like nitrate and phosphate with potential applications in agriculture and healthcare.
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Affiliation(s)
- Ujjawal Bairagi
- Department of Materials Science and Engineering, Indian Institute of Technology, Delhi, New Delhi 110016, India
| | - Josemon Jacob
- Department of Materials Science and Engineering, Indian Institute of Technology, Delhi, New Delhi 110016, India
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Bahadoran Z, Mirmiran P, Kashfi K, Ghasemi A. Lost-in-Translation of Metabolic Effects of Inorganic Nitrate in Type 2 Diabetes: Is Ascorbic Acid the Answer? Int J Mol Sci 2021; 22:4735. [PMID: 33947005 PMCID: PMC8124635 DOI: 10.3390/ijms22094735] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 04/25/2021] [Accepted: 04/27/2021] [Indexed: 12/14/2022] Open
Abstract
Beneficial metabolic effects of inorganic nitrate (NO3-) and nitrite (NO2-) in type 2 diabetes mellitus (T2DM) have been documented in animal experiments; however, this is not the case for humans. Although it has remained an open question, the redox environment affecting the conversion of NO3- to NO2- and then to NO is suggested as a potential reason for this lost-in-translation. Ascorbic acid (AA) has a critical role in the gastric conversion of NO2- to NO following ingestion of NO3-. In contrast to AA-synthesizing species like rats, the lack of ability to synthesize AA and a lower AA body pool and plasma concentrations may partly explain why humans with T2DM do not benefit from NO3-/NO2- supplementation. Rats also have higher AA concentrations in their stomach tissue and gastric juice that can significantly potentiate gastric NO2--to-NO conversion. Here, we hypothesized that the lack of beneficial metabolic effects of inorganic NO3- in patients with T2DM may be at least in part attributed to species differences in AA metabolism and also abnormal metabolism of AA in patients with T2DM. If this hypothesis is proved to be correct, then patients with T2DM may need supplementation of AA to attain the beneficial metabolic effects of inorganic NO3- therapy.
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Affiliation(s)
- Zahra Bahadoran
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran; (Z.B.); (P.M.)
| | - Parvin Mirmiran
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran; (Z.B.); (P.M.)
| | - Khosrow Kashfi
- Department of Molecular, Cellular and Biomedical Sciences, Sophie Davis School of Biomedical Education, City University of New York School of Medicine, New York, NY 10031, USA;
| | - Asghar Ghasemi
- Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran 19395-4763, Iran
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Afzali H, Khaksari M, Jeddi S, Kashfi K, Abdollahifar MA, Ghasemi A. Acidified Nitrite Accelerates Wound Healing in Type 2 Diabetic Male Rats: A Histological and Stereological Evaluation. Molecules 2021; 26:1872. [PMID: 33810327 PMCID: PMC8037216 DOI: 10.3390/molecules26071872] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Revised: 03/09/2021] [Accepted: 03/23/2021] [Indexed: 01/13/2023] Open
Abstract
Impaired skin nitric oxide production contributes to delayed wound healing in type 2 diabetes (T2D). This study aims to determine improved wound healing mechanisms by acidified nitrite (AN) in rats with T2D. Wistar rats were assigned to four subgroups: Untreated control, AN-treated control, untreated diabetes, and AN-treated diabetes. AN was applied daily from day 3 to day 28 after wounding. On days 3, 7, 14, 21, and 28, the wound levels of vascular endothelial growth factor (VEGF) were measured, and histological and stereological evaluations were performed. AN in diabetic rats increased the numerical density of basal cells (1070 ± 15.2 vs. 936.6 ± 37.5/mm3) and epidermal thickness (58.5 ± 3.5 vs. 44.3 ± 3.4 μm) (all p < 0.05); The dermis total volume and numerical density of fibroblasts at days 14, 21, and 28 were also higher (all p < 0.05). The VEGF levels were increased in the treated diabetic wounds at days 7 and 14, as was the total volume of fibrous tissue and hydroxyproline content at days 14 and 21 (all p < 0.05). AN improved diabetic wound healing by accelerating the dermis reconstruction, neovascularization, and collagen deposition.
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Affiliation(s)
- Hamideh Afzali
- Endocrinology and Metabolism Research, and Physiology Research Centers, Kerman University of Medical Sciences, Kerman 7616913555, Iran; (H.A.); (M.K.)
- Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran;
| | - Mohammad Khaksari
- Endocrinology and Metabolism Research, and Physiology Research Centers, Kerman University of Medical Sciences, Kerman 7616913555, Iran; (H.A.); (M.K.)
| | - Sajad Jeddi
- Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran;
| | - Khosrow Kashfi
- Department of Molecular, Cellular and Biomedical Sciences, Sophie Davis School of Biomedical Education, City University of New York School of Medicine, New York, NY 10031, USA;
| | - Mohammad-Amin Abdollahifar
- Department of Biology and Anatomical Sciences, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran
| | - Asghar Ghasemi
- Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran;
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Abstract
The prevalence of cardiovascular and metabolic disease coupled with kidney dysfunction is increasing worldwide. This triad of disorders is associated with considerable morbidity and mortality as well as a substantial economic burden. Further understanding of the underlying pathophysiological mechanisms is important to develop novel preventive or therapeutic approaches. Among the proposed mechanisms, compromised nitric oxide (NO) bioactivity associated with oxidative stress is considered to be important. NO is a short-lived diatomic signalling molecule that exerts numerous effects on the kidneys, heart and vasculature as well as on peripheral metabolically active organs. The enzymatic L-arginine-dependent NO synthase (NOS) pathway is classically viewed as the main source of endogenous NO formation. However, the function of the NOS system is often compromised in various pathologies including kidney, cardiovascular and metabolic diseases. An alternative pathway, the nitrate-nitrite-NO pathway, enables endogenous or dietary-derived inorganic nitrate and nitrite to be recycled via serial reduction to form bioactive nitrogen species, including NO, independent of the NOS system. Signalling via these nitrogen species is linked with cGMP-dependent and independent mechanisms. Novel approaches to restoring NO homeostasis during NOS deficiency and oxidative stress have potential therapeutic applications in kidney, cardiovascular and metabolic disorders.
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Bahadoran Z, Norouzirad R, Mirmiran P, Gaeini Z, Jeddi S, Shokri M, Azizi F, Ghasemi A. Effect of inorganic nitrate on metabolic parameters in patients with type 2 diabetes: A 24-week randomized double-blind placebo-controlled clinical trial. Nitric Oxide 2020; 107:58-65. [PMID: 33340674 DOI: 10.1016/j.niox.2020.12.005] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2020] [Revised: 11/24/2020] [Accepted: 12/14/2020] [Indexed: 12/19/2022]
Abstract
AIM In this randomized placebo-controlled clinical trial, effect of oral inorganic nitrate (NO3-) on metabolic parameters was assessed in patients with type 2 diabetes mellitus (T2DM). METHODS Seventy-four eligible patients with T2DM were randomly assigned to NO3--rich beetroot powder (5 g/d contains ~250 mg NO3-) and placebo groups to complete intervention over a 24-week period. Blood HbA1c, fasting serum glucose, insulin, C-peptide, as well as lipid profile were assessed at baseline and again at weeks 4, 12, and 24; indices of insulin resistance were also calculated. To assess safety of long-term oral NO3-, liver and renal function tests were measured. An intention-to-treat approach was used for data analysis. To compare effect of intervention over time between the groups (time×group), repeated measures generalized estimating equation (GEE) linear regression models were used. RESULTS Mean age of the participants was 54.0 ± 8.5 (47.9% were male) and mean duration of diabetes was 8.5 ± 6.1 years. A total of 64 patients (n = 35 in beetroot group and n = 29 in placebo group) completed at least two visits and were included in the analyses. No significant difference was observed between the groups for glycemic and lipid parameters over time. Liver and renal function tests, as safety outcome measures, showed no undesirable changes during the study follow-up. CONCLUSION Supplementation with inorganic NO3- had no effect on metabolic parameters in patients with T2DM.
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Affiliation(s)
- Zahra Bahadoran
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Reza Norouzirad
- Department of Biochemistry, School of Paramedical Sciences, Dezful University of Medical Sciences, Dezful, Iran
| | - Parvin Mirmiran
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zahra Gaeini
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sajad Jeddi
- Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Majid Shokri
- Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fereidoun Azizi
- Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Asghar Ghasemi
- Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Burleigh MC, Sculthorpe N, Henriquez FL, Easton C. Nitrate-rich beetroot juice offsets salivary acidity following carbohydrate ingestion before and after endurance exercise in healthy male runners. PLoS One 2020; 15:e0243755. [PMID: 33320868 PMCID: PMC7737958 DOI: 10.1371/journal.pone.0243755] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Accepted: 11/25/2020] [Indexed: 11/23/2022] Open
Abstract
There have been recent calls for strategies to improve oral health in athletes. High carbohydrate diets, exercise induced dehydration and transient perturbations to immune function combine to increase oral disease risk in this group. We tested whether a single dose of nitrate (NO3-) would offset the reduction in salivary pH following carbohydrate ingestion before and after an exercise bout designed to cause mild dehydration. Eleven trained male runners (V˙O2max 53 ± 9 ml∙kg-1∙min-1, age 30 ± 7 years) completed a randomised placebo-controlled study comprising four experimental trials. Participants ingested the following fluids one hour before each trial: (a) 140 ml of water (negative-control), (b) 140 ml of water (positive-control), (c) 140 ml of NO3- rich beetroot juice (~12.4 mmol NO3-) (NO3- trial) or (d) 140 ml NO3- depleted beetroot juice (placebo-trial). During the negative-control trial, participants ingested 795 ml of water in three equal aliquots: before, during, and after 90 min of submaximal running. In the other trials they received 795 ml of carbohydrate supplements in the same fashion. Venous blood was collected before and after the exercise bout and saliva was sampled before and repeatedly over the 20 min following carbohydrate or water ingestion. As expected, nitrite (NO2-) and NO3- were higher in plasma and saliva during the NO3- trial than all other trials (all P<0.001). Compared to the negative-control, salivary-pH was significantly reduced following the ingestion of carbohydrate in the positive-control and placebo trials (both P <0.05). Salivary-pH was similar between the negative-control and NO3- trials before and after exercise despite ingestion of carbohydrate in the NO3- trial (both P≥0.221). Ingesting NO3- attenuates the expected reduction in salivary-pH following carbohydrate supplements and exercise-induced dehydration. NO3- should be considered by athletes as a novel nutritional strategy to reduce the risk of developing acidity related oral health conditions.
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Affiliation(s)
- Mia C. Burleigh
- Institute of Clinical Health and Exercise Sciences, University of the West of Scotland, Blantyre, Scotland
| | - Nicholas Sculthorpe
- Institute of Clinical Health and Exercise Sciences, University of the West of Scotland, Blantyre, Scotland
| | - Fiona L. Henriquez
- Institute of Biomedical and Environmental Health Research, University of the West of Scotland, Blantyre, Scotland
| | - Chris Easton
- Institute of Clinical Health and Exercise Sciences, University of the West of Scotland, Blantyre, Scotland
- * E-mail:
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Bahadoran Z, Mirmiran P, Carlström M, Norouzirad R, Jeddi S, Azizi F, Ghasemi A. Different Pharmacokinetic Responses to an Acute Dose of Inorganic Nitrate in Patients with Type 2 Diabetes. Endocr Metab Immune Disord Drug Targets 2020; 21:878-886. [PMID: 32787767 DOI: 10.2174/1871530320666200813135251] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Revised: 06/21/2020] [Accepted: 07/16/2020] [Indexed: 11/22/2022]
Abstract
AIM In this study, we aimed to compare the pharmacokinetics of nitrate (NO3) in patients with type 2 diabetes mellitus (T2DM) and healthy adults. Potential effects of salivary nitrate reductase (NR) activity on cardiometabolic responses to an acute dose of NO3 was also assessed. METHODS Nine healthy adults and nine T2DM patients were recruited to consume a NO3-rich breakfast (~410 mg NO3). Pharmacokinetics of NO3 were examined using repeated measurements of NOx (nitrate+ nitrite) concentrations of serum and saliva over 8 hours and NO3 concentrations of spot and 24-h urine samples. Cardiometabolic parameters, including serum levels of glucose, insulin, and triglycerides as well as blood pressure were also measured. RESULTS Compared to patients with T2DM, serum NOx concentration (Δ1= 16.7 vs. 4.4 μmol/L, P=0.057) of healthy subjects sharply increased within 1 hour after NO3 loading. Healthy subjects had a higher NR activity index, and higher peak salivary NO3 concentration with a lower time to peak. Diabetic patients with high- compared to low-NR values had a higher whole-body NOx exposure (103±31.4 vs. 58.9±22.1 μmol.h/L); they also showed a better glycemic response and more reduction of blood pressure following ingestion of a NO3-rich meal. CONCLUSION T2DM may be associated with a different pattern of NOx pharmacokinetics (especially salivary NOx metabolism). Salivary NR activity may have a critical role in postprandial metabolism of NO3, and diabetic patients with higher NR activity may take more advantages from NO3 supplementation.
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Affiliation(s)
- Zahra Bahadoran
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Parvin Mirmiran
- Department of Clinical Nutrition and Human Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mattias Carlström
- Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
| | - Reza Norouzirad
- Department of Biochemistry, School of Paramedical Sciences, Dezful University of Medical Sciences, Dezful, Iran
| | - Sajad Jeddi
- Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fereidoun Azizi
- Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Asghar Ghasemi
- Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Sokolovska J, Dekante A, Baumane L, Pahirko L, Valeinis J, Dislere K, Rovite V, Pirags V, Sjakste N. Nitric oxide metabolism is impaired by type 1 diabetes and diabetic nephropathy. Biomed Rep 2020; 12:251-258. [PMID: 32257188 DOI: 10.3892/br.2020.1288] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Accepted: 12/16/2019] [Indexed: 12/14/2022] Open
Abstract
Diabetes leads to reduced nitric oxide bioavailability, resulting in endothelial dysfunction. However, overproduction of nitric oxide due to hyperglycaemia is associated with oxidative stress and tissue damage. The objective of this study was to characterise nitric oxide production (NO) and added nitrite and nitrate (NO2 -+NO3 -) concentration in the blood and urine of patients with and without diabetic nephropathy. A total of 268 patients with type 1 diabetes and 69 healthy subjects were included. Diabetic nephropathy was defined as macroalbuminuria and/or estimated glomerular filtration rate below 60 ml/min/1.73 cm2. NO2 -+NO3 - concentration was measured by Griess reaction. Production of NO was detected by electron paramagnetic resonance spectroscopy. Blood NO was demonstrated to be higher (P<0.001) and serum NO2 -+NO3 - was lower (P=0.003) in patients with type 1 diabetes and no nephropathy vs. healthy subjects. However, serum NO2 -+NO3 - concentration in patients with diabetes and nephropathy did not differ from the levels observed in healthy controls. Urine excretion of NO2 -+NO3 - was significantly decreased in patients with nephropathy, compared with patients without diabetic kidney disease (P=0.006) and healthy subjects (P=0.010). A significant positive correlation was observed between urine NO2 -+NO3 - and estimated glomerular filtration rate in patients with type 1 diabetes (P=0.002) and healthy subjects (P=0.008). Estimated glomerular filtration rate, albuminuria and diabetic nephropathy status were significant predictors of the whole blood NO and NO2 -+NO3 - in serum and urine in patients with type 1 diabetes, as identified by linear regression models. The present study concludes that NO metabolism is impaired by type 1 diabetes and diabetic nephropathy.
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Affiliation(s)
- Jelizaveta Sokolovska
- Laboratory for Personalized Medicine, Faculty of Medicine, University of Latvia, LV-1004 Riga, Latvia
| | - Alise Dekante
- Laboratory for Personalized Medicine, Faculty of Medicine, University of Latvia, LV-1004 Riga, Latvia.,Internal Medicine Clinic, Pauls Stradins Clinical University Hospital, LV-1002 Riga, Latvia
| | - Larisa Baumane
- Biochemistry Team, Latvian Institute of Organic Synthesis, LV-1006 Riga, Latvia
| | - Leonora Pahirko
- Laboratory for Statistics Research and Data Analysis, Faculty of Physics, Mathematics and Optometry, University of Latvia, LV-1004 Riga, Latvia
| | - Janis Valeinis
- Laboratory for Statistics Research and Data Analysis, Faculty of Physics, Mathematics and Optometry, University of Latvia, LV-1004 Riga, Latvia
| | - Kristine Dislere
- Laboratory of Genomics and Bioinformatics, Institute of Biology, University of Latvia, LV-1004 Riga, Latvia
| | - Vita Rovite
- Database of Latvian Population, Latvian Biomedical Research and Study Centre, LV-1067 Riga, Latvia
| | - Valdis Pirags
- Laboratory for Personalized Medicine, Faculty of Medicine, University of Latvia, LV-1004 Riga, Latvia.,Internal Medicine Clinic, Pauls Stradins Clinical University Hospital, LV-1002 Riga, Latvia.,Database of Latvian Population, Latvian Biomedical Research and Study Centre, LV-1067 Riga, Latvia
| | - Nikolajs Sjakste
- Department of Medical Biochemistry, Faculty of Medicine, University of Latvia, LV-1004 Riga, Latvia
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Sodium nitrate preconditioning prevents progression of the neuropathic pain in streptozotocin-induced diabetes Wistar rats. J Diabetes Metab Disord 2020; 19:105-113. [PMID: 32550160 DOI: 10.1007/s40200-019-00481-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Accepted: 12/17/2019] [Indexed: 12/14/2022]
Abstract
Purpose The purpose of the study was to evaluate the possible protective effects of low dose sodium nitrate preconditioning on the peripheral neuropathy in streptozotocin (STZ)-induced diabetic model. Methods Male Wistar rats were randomly divided into five groups: control (no intervention), control treated sodium nitrate (100 mg/L in drinking water), diabetic (no intervention), diabetic treated NPH insulin (2-4 U), and diabetic treated sodium nitrate (100 mg/L in drinking water). Diabetes was induced by intraperitoneal injection of STZ (60 mg/kg). All interventions were done for 60 days immediately following diabetes confirmation. Thermal and mechanical algesia thresholds were measured by means of hot-plate test, von Frey test, and tail-withdrawal test before the diabetic induction and after diabetes confirmation. At the end of the experiment, serum NOx level and serum insulin level were assessed. Blood glucose concentration and body weight have recorded at the base and duration of the experiment. Results Both hypoalgesia, hyperalgesia along with allodynia developed in diabetic rats. Significant alterations including, decrease in tail withdrawal latency (30th day), decreased mechanical threshold (60th day), and an increase in hot plate latency (61st day) were displayed in diabetic rats compared to control rats. Nitrate and insulin preconditioning produced protective effects against diabetes-induced peripheral neuropathy. Data analysis also showed a significant increase in glucose level as well as a considerable reduction in serum insulin and body weight of diabetic rats, which restored by both insulin and nitrate preconditioning. Conclusion Sodium nitrate preconditioning produces a protective effect in diabetic neuropathy, which may be mediated by its antihyperglycemic effects and increased serum insulin level.
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Fischer A, Lüersen K, Schultheiß G, de Pascual-Teresa S, Mereu A, Ipharraguerre IR, Rimbach G. Supplementation with nitrate only modestly affects lipid and glucose metabolism in genetic and dietary-induced murine models of obesity. J Clin Biochem Nutr 2019; 66:24-35. [PMID: 32001953 PMCID: PMC6983433 DOI: 10.3164/jcbn.19-43] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Accepted: 09/11/2019] [Indexed: 01/07/2023] Open
Abstract
To gain a better understanding of how nitrate may affect carbohydrate and lipid metabolism, female wild-type mice were fed a high-fat, high-fructose diet supplemented with either 0, 400, or 800 mg nitrate/kg diet for 28 days. Additionally, obese female db/db mice were fed a 5% fat diet supplemented with the same levels and source of nitrate. Nitrate decreased the sodium-dependent uptake of glucose by ileal mucosa in wild-type mice. Moreover, nitrate significantly decreased triglyceride content and mRNA expression levels of Pparγ in liver and Glut4 in skeletal muscle. Oral glucose tolerance as well as plasma cholesterol, triglyceride, insulin, leptin, glucose and the activity of ALT did not significantly differ between experimental groups but was higher in db/db mice than in wild-type mice. Nitrate changed liver fatty acid composition and mRNA levels of Fads only slightly. Further hepatic genes encoding proteins involved in lipid and carbohydrate metabolism were not significantly different between the three groups. Biomarkers of inflammation and autophagy in the liver were not affected by the different dietary treatments. Overall, the present data suggest that short-term dietary supplementation with inorganic nitrate has only modest effects on carbohydrate and lipid metabolism in genetic and dietary-induced mouse models of obesity.
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Affiliation(s)
- Alexandra Fischer
- Institute of Human Nutrition and Food Science, Food Science, University of Kiel, Hermann-Rodewald-Strasse 6, 24118 Kiel, Germany
| | - Kai Lüersen
- Institute of Human Nutrition and Food Science, Food Science, University of Kiel, Hermann-Rodewald-Strasse 6, 24118 Kiel, Germany
| | - Gerhard Schultheiß
- Animal Welfare Officer, University of Kiel, Hermann-Rodewald-Strasse 12, 24118 Kiel, Germany
| | - Sonia de Pascual-Teresa
- Department of Metabolism and Nutrition, Institute of Food Science, Food Technology and Nutrition (ICTAN-CSIC), José Antonio Novais 10, 28040 Madrid, Spain
| | - Alessandro Mereu
- Yara Iberian, C/ Infanta Mercedes 31 - 2nd floor, 28020 Madrid, Spain
| | - Ignacio R Ipharraguerre
- Institute of Human Nutrition and Food Science, Food Science, University of Kiel, Hermann-Rodewald-Strasse 6, 24118 Kiel, Germany
| | - Gerald Rimbach
- Institute of Human Nutrition and Food Science, Food Science, University of Kiel, Hermann-Rodewald-Strasse 6, 24118 Kiel, Germany
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Reciprocal regulation of sulfite oxidation and nitrite reduction by mitochondrial sulfite oxidase. Nitric Oxide 2019; 89:22-31. [PMID: 31002874 DOI: 10.1016/j.niox.2019.04.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Revised: 04/08/2019] [Accepted: 04/11/2019] [Indexed: 01/08/2023]
Abstract
The oxygen-independent nitrate-nitrite-nitric oxide (NO) pathway is considered as a substantial source of NO in mammals. Dietary nitrate/nitrite are distributed throughout the body and reduced to NO by the action of various enzymes. The intermembrane spaced (IMS), molybdenum cofactor-dependent sulfite oxidase (SO) was shown to catalyze such a nitrite reduction. In this study we asked whether the primary function of SO - sulfite oxidation - and its novel function - nitrite reduction - impact each other. First, we utilized benzyl viologen as artificial electron donor to investigate steady state NO synthesis by SO and found fast (kcat = 14 s-1) nitrite reduction of SO full-length and its isolated molybdenum domain at pH 6.5. Next, we determined the impact of nitrite on pre-steady state kinetics in SO catalysis and identified nitrite as a pH-dependent inhibitor of SO reductive and oxidative half reaction. Finally, we report on the time-dependent formation of the paramagnetic Mo(V) species following nitrite reduction and demonstrate that sulfite inhibits nitrite reduction. In conclusion, we propose a pH-dependent reciprocal regulation of sulfite oxidation and nitrite reduction by each substrate, thus facilitating quick responses to hypoxia induced changes in the IMS, which may function in protecting the cell from reactive oxygen species production.
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Dietary nitrate supplementation alters the oral microbiome but does not improve the vascular responses to an acute nitrate dose. Nitric Oxide 2019; 89:54-63. [DOI: 10.1016/j.niox.2019.04.010] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Revised: 04/09/2019] [Accepted: 04/29/2019] [Indexed: 12/18/2022]
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Khorasani V, Jeddi S, Yaghmaei P, Tohidi M, Ghasemi A. Effect of long-term sodium nitrate administration on diabetes-induced anemia and glucose homeostasis in obese type 2 diabetic male rats. Nitric Oxide 2019; 86:21-30. [DOI: 10.1016/j.niox.2019.02.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2018] [Revised: 02/04/2019] [Accepted: 02/13/2019] [Indexed: 01/20/2023]
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Bahadoran Z, Mirmiran P, Jeddi S, Carlström M, Azizi F, Ghasemi A. Circulating markers of nitric oxide homeostasis and cardiometabolic diseases: insights from population-based studies. Free Radic Res 2019; 53:359-376. [PMID: 30821533 DOI: 10.1080/10715762.2019.1587168] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Emerging data suggest that impaired nitric oxide (NO) homeostasis has a key role in development of cardiometabolic disorders. The association between circulating levels of NO metabolites, i.e. nitrate and nitrite (NOx), and risk of chronic diseases has not yet been fully clarified. This work aims to address epidemiologic aspects of NO metabolism and discusses different physiologic and pathophysiologic conditions influencing circulating NOx. Further, cross-sectional associations of serum NOx with metabolic disorders are described and along the way, potential short-term and long-term power of serum NOx for predicting cardiometabolic outcomes are reviewed. Results from population-based studies show that circulating NOx is affected by aging, smoking habits, pregnancy, menopause status, thyroid hormones, and various pathologic conditions including type 2 diabetes, insulin resistance, hypertension, and renal dysfunction. Lifestyle factors, especially dietary habits, but also smoking habits and the degree of physical activity influence NO homeostasis and the circulating levels of NOx. Elevated serum NOx, due to increased iNOS activity, is associated with increased incidence of metabolic syndrome, different obesity phenotypes, and cardiovascular events.
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Affiliation(s)
- Zahra Bahadoran
- a Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences , Tehran , Iran
| | - Parvin Mirmiran
- b Department of Clinical Nutrition and Diet Therapy, Faculty of Nutrition Sciences and Food Technology , National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences , Tehran , Iran
| | - Sajad Jeddi
- c Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences , Tehran , Iran
| | - Mattias Carlström
- d Department of Physiology and Pharmacology , Karolinska Institutet , Stockholm , Sweden
| | - Fereidoun Azizi
- e Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences , Tehran , Iran
| | - Asghar Ghasemi
- c Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences , Tehran , Iran
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Beneficial treatment effects of dietary nitrate supplementation on testicular injury in streptozotocin-induced diabetic male rats. Reprod Biomed Online 2019; 39:357-371. [PMID: 30952494 DOI: 10.1016/j.rbmo.2018.11.027] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2018] [Revised: 11/14/2018] [Accepted: 11/27/2018] [Indexed: 01/01/2023]
Abstract
RESEARCH QUESTION Do low doses of dietary nitrate help to attenuate the progression of diabetic reproductive disorders in streptozotocin-induced diabetic male rats? DESIGN Fifty male Wistar rats were divided into five groups: controls receiving distilled water; controls receiving 100 mg/l nitrate in distilled water; diabetic rats receiving distilled water; diabetic rats receiving insulin 2-4 U/day of neutral protamine hagedorn insulin; and diabetic rats receiving 100 mg/l nitrate in distilled water. Diabetes was induced by 45 mg/kg streptozotocin. Nitrate and insulin treatment were started 4 weeks after diabetes induction for 8 weeks. Serum insulin, nitrogen oxide, stereology of testis, apoptosis, sperm parameters, and mRNA expression of Pdcd4, Pacs2, p53 and miR-449a were assessed at the end of the study. RESULTS Blood glucose, apoptotic index of seminiferous tubules and expression of p53, Pdcd4, and Pacs2 mRNA were significantly higher in the diabetic rats (P < 0.001). Decreased body weight, serum insulin and nitrogen oxide level, and miR-449a were observed in the diabetic group (P < 0.01 for insulin; P < 0.001 for others). Most sperm parameters and stereological results differed between diabetic and control rats; nitrate recovered almost all these alterations, including dead spermatozoa, sperm motility grade, sperm deformity index, spermatozoa with damaged DNA, malformations in abnormal spermatozoa, total volume of seminiferous tubule, germinal epithelium, capsule, lumen, interstitial tissue, seminiferous tubule diameter, germinal epithelium height, the number of spermatogenic, Sertoli and Leydig cells. CONCLUSIONS Treatment with sodium nitrate could modulate apoptosis, which is a major cause of diabetic testicular disorder. These experiments suggest that nitric oxide plays an important role in the function of the reproductive system.
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Ragy MM, Ahmed SM. Protective effects of either C-peptide or l-arginine on pancreatic β-cell function, proliferation, and oxidative stress in streptozotocin-induced diabetic rats. J Cell Physiol 2018; 234:11500-11510. [PMID: 30515793 DOI: 10.1002/jcp.27808] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2018] [Accepted: 11/01/2018] [Indexed: 12/11/2022]
Abstract
Diabetes and cardiometabolic risk factors including hypertension and dyslipidemia are the major threats to human health in the 21st century. Apoptosis in pancreatic tissue is one of the major causes of diabetes type 1 progression. The aim of this study was to investigate the effects of C-peptide or l-arginine on some cardiometabolic risk factors, pancreatic morphology, function and apoptosis, and the mechanisms of their actions. Forty adult male albino rats were divided into four equal groups: 1-control nondiabetic, 2-diabetic (no treatment), 3-diabetic + C-peptide, and 4-diabetic + l-arginine. Diabetes was induced by a single intraperitoneal injection of high dose streptozotocin. At the end of the experiment, sera glucose, insulin levels, total antioxidant capacity (TAC), malondialdehyde (MDA), nitric oxide (NO), and pancreatic MDA, TAC, and B-cell lymphoma 2 were measured. The morphology and proliferating activity of the pancreas were examined by hematoxylin and eosin histological stain, proliferative cell nuclear antigen (PCNA), and insulin antibodies. Our results showed that induction of diabetes caused hyperglycemia, dyslipidemia, and oxidative stress. However, administration of C-peptide or l-arginine significantly improved the pancreatic histopathology with a significant increase in the area % of insulin immunoreactivity, the number of PCNA immunopositive cells, the number of islets, and the diameter of islets compared with the diabetic group. C-peptide treatment of the diabetic rats completely corrected these errors, while l-arginine partially antagonized the above diabetic complications. So the administration of C-peptide as an adjuvant therapy in type 1 diabetes can significantly decrease apoptosis of pancreas and subsequent progression of diabetes complication.
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Affiliation(s)
- Merhan Mamdouh Ragy
- Department of Physiology, Faculty of Medicine, Minia University, Minia, Egypt
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Chang S, Hu L, Xu Y, Li X, Ma L, Feng X, Wang J, Zhang C, Wang S. Inorganic Nitrate Alleviates Total Body Irradiation-Induced Systemic Damage by Decreasing Reactive Oxygen Species Levels. Int J Radiat Oncol Biol Phys 2018; 103:945-957. [PMID: 30458235 DOI: 10.1016/j.ijrobp.2018.11.021] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Revised: 10/26/2018] [Accepted: 11/10/2018] [Indexed: 12/25/2022]
Abstract
PURPOSE To evaluate the protective effect of inorganic nitrate against systemic damage in a mouse model of total body gamma irradiation (TBI). METHODS AND MATERIALS C57BL/6 mice in the irradiation (IR) + NaNO3 group were pretreated with 2 mmol/L NaNO3 in their drinking water for 1 week before receiving 5 Gy irradiation. Animals that received only 5 Gy irradiation were designated as the IR group. Survival and body weight were monitored. The peripheral blood lymphocytes, heart, liver, lung, and submandibular gland were harvested and assessed. Reactive oxygen species (ROS) were measured in the lung and submandibular gland. We examined phosphorylated histone H2AX (p-H2AX) and p53-binding protein 1 (53BP1) as markers of early-stage DNA damage and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and Bax/caspase 3 mRNA expression as markers of apoptosis. RESULTS No improvement of survival was observed in the IR + NaNO3 group after TBI, but body weight loss after 5 Gy TBI was significantly attenuated in the IR + NaNO3 group. The levels of peripheral blood erythrocytes, leukocytes, and platelets at 7 days postirradiation recovered with nitrate treatment; moreover, the p-H2AX level in the peripheral blood lymphocytes was much lower in the IR + NaNO3 group at 2 and 4 hours post irradiation. In the lung and submandibular gland, the levels of p-H2AX, 53BP1 and ROS as well as TUNEL staining were significantly decreased in the IR + NaNO3 group compared with those in the IR group. Gene expression of Bax and caspase 3 was decreased in both the lung and submandibular gland with nitrate treatment, indicating attenuation of apoptosis. CONCLUSION Inorganic nitrate delivery could effectively prevent TBI-induced systemic damage. Nitrate-mediated decreases in ROS levels may contribute to this systemic protective effect.
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Affiliation(s)
- Shimin Chang
- Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China
| | - Liang Hu
- Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China
| | - Yipu Xu
- Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China
| | - Xiangchun Li
- Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China
| | - Linsha Ma
- Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China
| | - Xiaoyu Feng
- Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China
| | - Jingsong Wang
- Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China; Departments of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medical Sciences, Beijing, China
| | - Chunmei Zhang
- Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China
| | - Songlin Wang
- Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China; Departments of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medical Sciences, Beijing, China.
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Oghbaei H, Alipour MR, Hamidian G, Ahmadi M, Ghorbanzadeh V, Keyhanmanesh R. Two months sodium nitrate supplementation alleviates testicular injury in streptozotocin-induced diabetic male rats. Exp Physiol 2018; 103:1603-1617. [DOI: 10.1113/ep087198] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2018] [Accepted: 07/24/2018] [Indexed: 12/13/2022]
Affiliation(s)
- Hajar Oghbaei
- Department of physiology; Tabriz University of Medical Sciences; Tabriz Iran
| | - Mohammad Reza Alipour
- Tuberculosis and Lung Diseases Research Center; Tabriz University of Medical Sciences; Tabriz Iran
| | - Gholamreza Hamidian
- Department of Basic Sciences; Faculty of Veterinary Medicine; University of Tabriz; Tabriz Iran
| | - Mahdi Ahmadi
- Tuberculosis and Lung Diseases Research Center; Tabriz University of Medical Sciences; Tabriz Iran
| | - Vajihe Ghorbanzadeh
- Razi herbal medicines research center; Lorestan University of medical sciences; Khorramabad Iran
| | - Rana Keyhanmanesh
- Drug Applied Research Center; Tabriz University of Medical Sciences; Tabriz Iran
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Keyhanmanesh R, Hamidian G, Alipour MR, Ranjbar M, Oghbaei H. Protective effects of sodium nitrate against testicular apoptosis and spermatogenesis impairments in streptozotocin-induced diabetic male rats. Life Sci 2018; 211:63-73. [PMID: 30205097 DOI: 10.1016/j.lfs.2018.09.019] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2018] [Revised: 09/05/2018] [Accepted: 09/08/2018] [Indexed: 12/13/2022]
Abstract
AIMS As nitric oxide (NO) production is essential for insulin signaling, glucose uptake, endothelial function, and regulation of apoptosis, the loss of bioavailable NO may be a mechanism underlying the development of diabetes complication. Dietary nitrate acts as a substrate for NO generation, thus serving as a physiological source of NO. This study evaluated the therapeutic effects of nitrate supplementation on the apoptosis-induced testicular disorders in diabetic rats. MAIN METHODS Fifty male Wistar rats were divided into five groups; control, control with 100 mg/L nitrate in distilled drinking water, diabetes, diabetes treated with 2-4 U/day NPH insulin, diabetes treated with 100 mg/L nitrate in distilled drinking water. After 8 weeks, blood samples, testis, and epididymis were collected to assess the apoptosis process and the stereology of testis tissue, sperm motility, morphology and DNA fragmentation, and also mRNA expression of miR-449a, p53, Pdcd4, and Pacs2 mRNA, as well as serum glucose, insulin, and NOx levels were investigated. KEY FINDINGS The results of this study indicated that nitrate treatment ameliorated the sperm parameters, testicular morphometrical and stereological alterations, reduced blood glucose, the number of TUNEL positive cells and tubules, and testicular expressions of p53, Pdcd4, and Pacs2 mRNA as well as increased body weight, serum insulin and NOx levels, and testicular expression of miR-449a in streptozotocin-induced diabetic rats. SIGNIFICANCE Our in vivo evidence revealed that nitrate treatment may has a favorable effect as an exogenous NO donor on experimental diabetic testicular damages in which NO bioavailability is impaired.
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Affiliation(s)
- Rana Keyhanmanesh
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Gholamreza Hamidian
- Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran
| | | | - Minoo Ranjbar
- Department of Midwifery, Bonab Branch, Islamic Azad University, Bonab, Iran
| | - Hajar Oghbaei
- Deptartment of Physiology, Tabriz University of Medical Sciences, Tabriz, Iran.
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Effect of long-term nitrite administration on browning of white adipose tissue in type 2 diabetic rats: A stereological study. Life Sci 2018; 207:219-226. [PMID: 29898382 DOI: 10.1016/j.lfs.2018.06.012] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2018] [Revised: 05/27/2018] [Accepted: 06/09/2018] [Indexed: 12/25/2022]
Abstract
INTRODUCTION Nitric oxide (NO) deficiency is associated with obesity and type 2 diabetes. Nitrite, a NO donor, is considered as a new therapeutic agent in diabetes. This study aims at determining effects of long-term nitrite administration on browning of white adipose tissue (WAT) in type 2 diabetic rats. METHODS Male rats were divided into 4 groups: Control, control + nitrite, diabetes, and diabetes + nitrite. Sodium nitrite (50 mg/L in drinking water) was administered for 3 months. Body weight was measured weekly. Fasting serum levels of glucose and nitric oxide metabolites (NOx) were measured monthly. Histological evaluations and measurement of cyclic guanosine monophosphate (cGMP) and NOx levels in adipose tissue were done at the end of the study. RESULTS Nitrite decreased serum glucose concentration and body weight gain in diabetic rats by 27.6% and 37.9%, respectively. In diabetic rats, nitrite increased NOx and cGMP levels in inguinal WAT by 95.7% and 33.1%, respectively. Numerical density in WAT of nitrite-treated diabetic rats was higher than in diabetic ones (995 ± 83 vs. 2513 ± 256 cell/mm3, P < 0.001); in addition, total surface area (4.84 ± 0.32 vs. 44.26 ± 9.7, mm2, P < 0.001) and volume of inguinal beige adipose tissue (7.2 ± 0.49 vs. 66.4 ± 14.51 mm3, <0.001) were higher in nitrite-treated diabetic rats compared to diabetic ones. CONCLUSIONS Favorable effects of long-term nitrite administration in obese type 2 diabetic rats is, at least in part, due to browning of WAT and also associated with increased NOx and cGMP level in adipose tissue. These findings may have potential applications for management of diabesity.
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Burleigh MC, Liddle L, Monaghan C, Muggeridge DJ, Sculthorpe N, Butcher JP, Henriquez FL, Allen JD, Easton C. Salivary nitrite production is elevated in individuals with a higher abundance of oral nitrate-reducing bacteria. Free Radic Biol Med 2018; 120:80-88. [PMID: 29550328 DOI: 10.1016/j.freeradbiomed.2018.03.023] [Citation(s) in RCA: 70] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2017] [Revised: 02/05/2018] [Accepted: 03/13/2018] [Indexed: 12/21/2022]
Abstract
Nitric oxide (NO) can be generated endogenously via NO synthases or via the diet following the action of symbiotic nitrate-reducing bacteria in the oral cavity. Given the important role of NO in smooth muscle control there is an intriguing suggestion that cardiovascular homeostasis may be intertwined with the presence of these bacteria. Here, we measured the abundance of nitrate-reducing bacteria in the oral cavity of 25 healthy humans using 16S rRNA sequencing and observed, for 3.5 h, the physiological responses to dietary nitrate ingestion via measurement of blood pressure, and salivary and plasma NO metabolites. We identified 7 species of bacteria previously known to contribute to nitrate-reduction, the most prevalent of which were Prevotella melaninogenica and Veillonella dispar. Following dietary nitrate supplementation, blood pressure was reduced and salivary and plasma nitrate and nitrite increased substantially. We found that the abundance of nitrate-reducing bacteria was associated with the generation of salivary nitrite but not with any other measured variable. To examine the impact of bacterial abundance on pharmacokinetics we also categorised our participants into two groups; those with a higher abundance of nitrate reducing bacteria (> 50%), and those with a lower abundance (< 50%). Salivary nitrite production was lower in participants with lower abundance of bacteria and these individuals also exhibited slower salivary nitrite pharmacokinetics. We therefore show that the rate of nitrate to nitrite reduction in the oral cavity is associated with the abundance of nitrate-reducing bacteria. Nevertheless, higher abundance of these bacteria did not result in an exaggerated plasma nitrite response, the best known marker of NO bioavailability. These data from healthy young adults suggest that the abundance of oral nitrate-reducing bacteria does not influence the generation of NO through the diet, at least when the host has a functional minimum threshold of these microorganisms.
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Affiliation(s)
- Mia C Burleigh
- Institute for Clinical Exercise and Health Science, University of the West of Scotland, Hamilton, UK
| | - Luke Liddle
- Institute for Clinical Exercise and Health Science, University of the West of Scotland, Hamilton, UK
| | - Chris Monaghan
- Institute for Clinical Exercise and Health Science, University of the West of Scotland, Hamilton, UK
| | - David J Muggeridge
- Physical Activity and Health Group, School of Psychological Science and Health, University of Strathclyde, Glasgow, UK
| | - Nicholas Sculthorpe
- Institute for Clinical Exercise and Health Science, University of the West of Scotland, Hamilton, UK
| | - John P Butcher
- Institute of Biomedical and Environmental Health Research, University of the West of Scotland, Paisley, UK; Department of Life Sciences, School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK
| | - Fiona L Henriquez
- Institute of Biomedical and Environmental Health Research, University of the West of Scotland, Paisley, UK
| | - Jason D Allen
- Department of Kinesiology, Curry School of Education, University of Virginia, Charlottesville, VA 22904, USA
| | - Chris Easton
- Institute for Clinical Exercise and Health Science, University of the West of Scotland, Hamilton, UK.
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Bahadoran Z, Carlström M, Ghasemi A, Mirmiran P, Azizi F, Hadaegh F. Total antioxidant capacity of the diet modulates the association between habitual nitrate intake and cardiovascular events: A longitudinal follow-up in Tehran Lipid and Glucose Study. Nutr Metab (Lond) 2018; 15:19. [PMID: 29492096 PMCID: PMC5828061 DOI: 10.1186/s12986-018-0254-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2017] [Accepted: 02/13/2018] [Indexed: 12/31/2022] Open
Abstract
Background Considering the lack of data on the association between habitual dietary intakes of nitrate (NO3−) and nitrite (NO2−) and cardiovascular events, we assessed possible effects of dietary NO3− and NO2−, in the context of total antioxidant capacity (TAC) of the diet, with the risk of cardiovascular (CVD) outcomes. Methods Adult men and women without CVD (n = 2369) were recruited from the Tehran Lipid and Glucose Study and were followed for a mean of 6.7 years. Dietary NO3− and NO2− intakes, as well as dietary TAC and nitric oxide (NO) index were assessed at baseline (2006–2008). Multivariable-adjusted Cox proportional hazards regression models were used to estimate risk of CVD above and below median of dietary intakes of NO3−/NO2− and dietary TAC and NO index. Due to a significant interaction between NO3−/NO2− intake and TAC, stratified analyses were done for < and ≥ median dietary TAC. Results Daily mean (SD) dietary NO3− and NO2− intakes were 460 (195) and 9.5 (3.9) mg; mean (SD) dietary TAC and NO index was 1406 (740) and 338 (197) μmol trolox equivalent (TE)/100 g. In subjects with lower dietary TAC, higher intake of NO3− (≥ 430 mg/d) was accompanied with an increased risk of CVD (HR = 3.28, 95% CI = 1.54–6.99). There were no significant associations between dietary intakes of NO2−, TAC of the diet and NO index with the occurrence of CVD events during the study follow-up. Conclusion High habitual intake of NO3−, in the context of low TAC of the food, may be associated with the risk of CVD outcomes.
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Affiliation(s)
- Zahra Bahadoran
- 1Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No. 24, Sahid-Erabi St, Yemen St, Chamran Exp, Tehran, 19395-4763 Iran
| | - Mattias Carlström
- 2Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
| | - Asghar Ghasemi
- 3Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Parvin Mirmiran
- 1Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No. 24, Sahid-Erabi St, Yemen St, Chamran Exp, Tehran, 19395-4763 Iran
| | - Fereidoun Azizi
- 4Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Farzad Hadaegh
- 5Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Bahadoran Z, Mirmiran P, Azizi F, Ghasemi A. Nitrate-rich dietary supplementation during pregnancy: The pros and cons. Pregnancy Hypertens 2018. [PMID: 29523272 DOI: 10.1016/j.preghy.2017.12.010] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Inorganic nitrate (NO3) due to its potential endogenous conversion to nitric oxide (NO), is suggested as a compensatory fuel for disrupted NO pathways in the case of pathological stats during pregnancy. Dietary NO3-rich supplement in the NO-deficient pregnant women is now suggested as a more appealing choice with fewer off-target effects which can attenuate hypertension and preeclampsia, improve placental blood flow and subsequently enhance maternal and neonatal health. There is also an increasing public interest and common health claims regarding beneficial effects of NO3-rich dietary supplements like beetroot byproducts in pregnant women. Conversely, NO3-rich dietary supplementation during pregnancy may be accompanied with a wide range of unexpected maternal and fatal adverse outcomes such as methemoglobinemia, alteration in embryonic cells and malignant transformation, as well as thyroid disorders. In conclusion, use of dietary inorganic NO3 as a common supplement during pregnancy is currently on a long way from bench to bedside.
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Affiliation(s)
- Zahra Bahadoran
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Parvin Mirmiran
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Fereidoun Azizi
- Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Asghar Ghasemi
- Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Wang Z, Ando A, Takeuchi A, Ueda H. Effects of Cooking Conditions on the Relationships Among Oxalate, Nitrate, and Lutein in Spinach. FOOD SCIENCE AND TECHNOLOGY RESEARCH 2018. [DOI: 10.3136/fstr.24.421] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Affiliation(s)
- Zheng Wang
- Division of Vegetable Pest Management and Functional Analysis, Institute of Vegetable and Floriculture Science, National Agriculture and Food Research Organization
| | - Akira Ando
- Division of Vegetable Pest Management and Functional Analysis, Institute of Vegetable and Floriculture Science, National Agriculture and Food Research Organization
| | - Atsuko Takeuchi
- Division of Vegetable Pest Management and Functional Analysis, Institute of Vegetable and Floriculture Science, National Agriculture and Food Research Organization
| | - Hiroshi Ueda
- Division of Vegetable Pest Management and Functional Analysis, Institute of Vegetable and Floriculture Science, National Agriculture and Food Research Organization
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Ghasemi A, Jeddi S. Anti-obesity and anti-diabetic effects of nitrate and nitrite. Nitric Oxide 2017; 70:9-24. [PMID: 28804022 DOI: 10.1016/j.niox.2017.08.003] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2017] [Revised: 07/02/2017] [Accepted: 08/08/2017] [Indexed: 02/06/2023]
Abstract
Prevalence of obesity is increasing worldwide and type 2 diabetes to date is the most devastating complication of obesity. Decreased nitric oxide bioavailability is a feature of obesity and diabetes that links these two pathologies. Nitric oxide is synthesized both by nitric oxide synthase enzymes from l-arginine and nitric oxide synthase-independent from nitrate/nitrite. Nitric oxide production from nitrate/nitrite could potentially be used for nutrition-based therapy in obesity and diabetes. Nitric oxide deficiency also contributes to pathogeneses of cardiovascular disease and hypertension, which are associated with obesity and diabetes. This review summarizes pathways for nitric oxide production and focuses on the anti-diabetic and anti-obesity effects of the nitrate-nitrite-nitric oxide pathway. In addition to increasing nitric oxide production, nitrate and nitrite reduce oxidative stress, increase adipose tissue browning, have favorable effects on nitric oxide synthase expression, and increase insulin secretion, all effects that are potentially promising for management of obesity and diabetes. Based on current data, it could be suggested that amplifying the nitrate-nitrite-nitric oxide pathway is a diet-based strategy for increasing nitric oxide bioavailability and the management of these two interlinked conditions. Adding nitrate/nitrite to drugs that are currently used for managing diabetes (e.g. metformin) and possibly anti-obesity drugs may also enhance their efficacy.
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Affiliation(s)
- Asghar Ghasemi
- Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Sajad Jeddi
- Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Hypoxia in Obesity and Diabetes: Potential Therapeutic Effects of Hyperoxia and Nitrate. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2017; 2017:5350267. [PMID: 28607631 PMCID: PMC5457776 DOI: 10.1155/2017/5350267] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/04/2016] [Revised: 04/04/2017] [Accepted: 04/11/2017] [Indexed: 02/06/2023]
Abstract
The prevalence of obesity and diabetes is increasing worldwide. Obesity and diabetes are associated with oxidative stress, inflammation, endothelial dysfunction, insulin resistance, and glucose intolerance. Obesity, a chronic hypoxic state that is associated with decreased nitric oxide (NO) bioavailability, is one of the main causes of type 2 diabetes. The hypoxia-inducible factor-1α (HIF-1α) is involved in the regulation of several genes of the metabolic pathways including proinflammatory adipokines, endothelial NO synthase (eNOS), and insulin signaling components. It seems that adipose tissue hypoxia and NO-dependent vascular and cellular dysfunctions are responsible for other consequences linked to obesity-related disorders. Although hyperoxia could reverse hypoxic-related disorders, it increases the production of reactive oxygen species (ROS) and decreases the production of NO. Nitrate can restore NO depletion and has antioxidant properties, and recent data support the beneficial effects of nitrate therapy in obesity and diabetes. Although it seems reasonable to combine hyperoxia and nitrate treatments for managing obesity/diabetes, the combined effects have not been investigated yet. This review discusses some aspects of tissue oxygenation and the potential effects of hyperoxia and nitrate interventions on obesity/diabetes management. It can be proposed that concomitant use of hyperoxia and nitrate is justified for managing obesity and diabetes.
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Concurrent Beet Juice and Carbohydrate Ingestion: Influence on Glucose Tolerance in Obese and Nonobese Adults. J Nutr Metab 2017; 2017:6436783. [PMID: 28203456 PMCID: PMC5288523 DOI: 10.1155/2017/6436783] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2016] [Accepted: 12/12/2016] [Indexed: 01/09/2023] Open
Abstract
Insulin resistance and obesity are characterized by low nitric oxide (NO) bioavailability. Insulin sensitivity is improved with stimulation of NO generating pathways. Consumption of dietary nitrate (NO3−) increases NO formation, via NO3− reduction to nitrite (NO2−) by oral bacteria. We hypothesized that acute dietary nitrate (beet juice) ingestion improves insulin sensitivity in obese but not in nonobese adults. 12 nonobese (body mass index: 26.3 ± 0.8 kg/m2 (mean ± SE)) and 10 obese adults (34.0 ± 0.8 kg/m2) ingested beet juice, supplemented with 25 g of glucose (carbohydrate load: 75 g), with and without prior use of antibacterial mouthwash to inhibit NO3− reduction to NO2−. Blood glucose concentrations after beet juice and glucose ingestion were greater in obese compared with nonobese adults at 60 and 90 minutes (P = 0.004). Insulin sensitivity, as represented by the Matsuda Index (where higher values reflect greater insulin sensitivity), was lower in obese compared with nonobese adults (P = 0.009). Antibacterial mouthwash rinsing decreased insulin sensitivity in obese (5.7 ± 0.7 versus 4.9 ± 0.6) but not in nonobese (8.1 ± 1.0 versus 8.9 ± 0.9) adults (P = 0.048). In conclusion, insulin sensitivity was improved in obese but not in nonobese adults following coingestion of beet juice and glucose when oral bacteria nitrate reduction was not inhibited. Obese adults may benefit from ingestion of healthy nitrate-rich foods during meals.
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