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Li S, He W, Yau HH, Xie J, Zhu Y, Chen X, Zhang S, Zhang Y, Liao P, Liu H, Li L, Zhong L, Wang W. Outcomes of BTD vs. BCD as initial treatment of renal amyloid light-chain amyloidosis: a retrospective cohort study in China. Ren Fail 2025; 47:2453006. [PMID: 39995107 PMCID: PMC11863997 DOI: 10.1080/0886022x.2025.2453006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Revised: 01/06/2025] [Accepted: 01/08/2025] [Indexed: 02/26/2025] Open
Abstract
OBJECTIVES To compare the efficacy and safety of bortezomib with thalidomide and dexamethasone (BTD) and bortezomib with cyclophosphamide and dexamethasone (BCD) as the initial treatment for renal amyloid light chain (AL) amyloidosis in Chinese cohort. METHODS A cohort of 174 patients with AL amyloidosis was studied in Guangdong Provincial People's Hospital from January 2008 to August 2023. Propensity-score matching cases were applied to assess the outcomes of patients treated with BTD and BCD regimen. Primary outcomes were patients achieving hematologic response and organ responses, and the secondary endpoints were patients progressing to end-stage renal disease or all-cause death. RESULTS 44 Patients were included. The hematologic complete response rate (CR) in the BTD group was comparable between the groups of BTD group and BCD. However, the time to achieve hematologic CR was significantly shorter in the BTD group compared to the BCD group (4.97 vs. 7.71 mon, p = 0.010). Furthermore, when reaching hematologic response, the cumulative dose of bortezomib that standardized by body surface area (BSA) was lower in BTD group than in the BCD group (10.4 vs. 15.6 mg/m2, p = 0.013). There was no significant difference of renal and cardiac response between groups. However, post-treatment proteinuria levels after treatment were significantly lower in the BTD group compared to those in the BCD group (747 mg/24h vs. 2928 mg/24h, p = 0.048). CONCLUSIONS Compared to BCD regimen for renal AL amyloidosis, initial treatment with BTD regimen demonstrated similar rates of hematologic CR but showed superior reduction in proteinuria, reduced cumulative dose of bortezomib and faster time-to-response.
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Affiliation(s)
- Sheng Li
- School of Medicine, South China University of Technology, Guangzhou, China
- Department of Nephrology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Weiting He
- Department of Nephrology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Hok-him Yau
- Department of Nephrology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Jianteng Xie
- School of Medicine, South China University of Technology, Guangzhou, China
- Department of Nephrology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Yaxi Zhu
- Department of Nephrology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Xiaojie Chen
- Department of Nephrology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Shaogui Zhang
- Department of Nephrology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Yifan Zhang
- Department of Nephrology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Pengjun Liao
- Department of Hematopathology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Hui Liu
- Department of Radiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Liwen Li
- Department of Cardiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Liye Zhong
- Department of Hematopathology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Wenjian Wang
- School of Medicine, South China University of Technology, Guangzhou, China
- Department of Nephrology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
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Hashimoto K, Kamijo Y. Current Progress in Peritoneal Dialysis: A Narrative Review of Progress in Peritoneal Dialysis Fluid. Life (Basel) 2025; 15:279. [PMID: 40003688 PMCID: PMC11856993 DOI: 10.3390/life15020279] [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: 01/08/2025] [Revised: 02/07/2025] [Accepted: 02/10/2025] [Indexed: 02/27/2025] Open
Abstract
Peritoneal dialysis (PD) is a renal replacement therapy that removes solutes, electrolytes, and water via the infusion of dialysis fluid into the peritoneal cavity. However, the non-physiological composition of conventional PD fluids can cause peritoneal injury, leading to complications such as peritoneal fibrosis and encapsulating peritoneal sclerosis. This review highlights recent advancements in PD fluid formulations aimed at improving biocompatibility and reducing peritoneal damage. While glucose-based solutions remain the standard because of their affordability, their glucose degradation products (GDPs) and advanced glycation end-products significantly contribute to peritoneal fibrosis. Innovations, such as neutral pH and low-GDP solutions, have been developed to counter these effects, enhancing peritoneal integrity and preserving residual renal function. Alternative osmotic agents, such as icodextrin, offer superior ultrafiltration. Advancements in buffer formulations, including bicarbonate-based and bicarbonate/lactate combinations, have further enhanced the biocompatibility of PD fluids. Despite these progressions, challenges persist. Therefore, future research should prioritize patient-specific PD solutions to optimize long-term outcomes and minimize adverse effects.
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Affiliation(s)
- Koji Hashimoto
- Department of Nephrology, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto 390-8621, Nagano, Japan
| | - Yuji Kamijo
- Department of Nephrology, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto 390-8621, Nagano, Japan
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Zhou M, Zhang Y, Shi L, Li L, Zhang D, Gong Z, Wu Q. Activation and modulation of the AGEs-RAGE axis: Implications for inflammatory pathologies and therapeutic interventions - A review. Pharmacol Res 2024; 206:107282. [PMID: 38914383 DOI: 10.1016/j.phrs.2024.107282] [Citation(s) in RCA: 35] [Impact Index Per Article: 35.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Revised: 05/26/2024] [Accepted: 06/21/2024] [Indexed: 06/26/2024]
Abstract
Chronic inflammation is a common foundation for the development of many non-communicable diseases, particularly diabetes, atherosclerosis, and tumors. The activation of the axis involving Advanced Glycation End products (AGEs) and their receptor RAGE is a key promotive factor in the chronic inflammation process, influencing the pathological progression of these diseases. The accumulation of AGEs in the body results from an increase in glycation reactions and oxidative stress, especially pronounced in individuals with diabetes. By binding to RAGE, AGEs activate signaling pathways such as NF-κB, promoting the release of inflammatory factors, exacerbating cell damage and inflammation, and further advancing the formation of atherosclerotic plaques and tumor development. This review will delve into the molecular mechanisms by which the AGEs-RAGE axis activates chronic inflammation in the aforementioned diseases, as well as strategies to inhibit the AGEs-RAGE axis, aiming to slow or halt the progression of chronic inflammation and related diseases. This includes the development of AGEs inhibitors, RAGE antagonists, and interventions targeting upstream and downstream signaling pathways. Additionally, the early detection of AGEs levels and RAGE expression as biomarkers provides new avenues for the prevention and treatment of diabetes, atherosclerosis, and tumors.
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Affiliation(s)
- Mengzhou Zhou
- Hubei Key Laboratory of Industrial Microbiology, Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Key Laboratory of Fermentation Engineering (Ministry of Education), National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan, Hubei, 430068, China
| | - Yuyan Zhang
- Hubei Key Laboratory of Industrial Microbiology, Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Key Laboratory of Fermentation Engineering (Ministry of Education), National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan, Hubei, 430068, China
| | - Lin Shi
- Wuhan Caidian District Public Inspection and Testing Center, Wuhan, Hubei 430068, PR China
| | - Liangchao Li
- Hubei Key Laboratory of Industrial Microbiology, Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Key Laboratory of Fermentation Engineering (Ministry of Education), National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan, Hubei, 430068, China
| | - Duo Zhang
- Hubei Standardization and Quality Institute, Wuhan,Hubei 430068, PR China
| | - Zihao Gong
- Hubei Key Laboratory of Industrial Microbiology, Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Key Laboratory of Fermentation Engineering (Ministry of Education), National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan, Hubei, 430068, China
| | - Qian Wu
- Hubei Key Laboratory of Industrial Microbiology, Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), Key Laboratory of Fermentation Engineering (Ministry of Education), National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan, Hubei, 430068, China.
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Bansal S, Burman A, Tripathi AK. Advanced glycation end products: Key mediator and therapeutic target of cardiovascular complications in diabetes. World J Diabetes 2023; 14:1146-1162. [PMID: 37664478 PMCID: PMC10473940 DOI: 10.4239/wjd.v14.i8.1146] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Revised: 03/21/2023] [Accepted: 05/22/2023] [Indexed: 08/11/2023] Open
Abstract
The incidence of type 2 diabetes mellitus is growing in epidemic proportions and has become one of the most critical public health concerns. Cardiovascular complications associated with diabetes are the leading cause of morbidity and mortality. The cardiovascular diseases that accompany diabetes include angina, myocardial infarction, stroke, peripheral artery disease, and congestive heart failure. Among the various risk factors generated secondary to hyperglycemic situations, advanced glycation end products (AGEs) are one of the important targets for future diagnosis and prevention of diabetes. In the last decade, AGEs have drawn a lot of attention due to their involvement in diabetic patho-physiology. AGEs can be derived exogenously and endogenously through various pathways. These are a non-homogeneous, chemically diverse group of compounds formed non-enzymatically by condensation between carbonyl groups of reducing sugars and free amino groups of protein, lipids, and nucleic acid. AGEs mediate their pathological effects at the cellular and extracellular levels by multiple pathways. At the cellular level, they activate signaling cascades via the receptor for AGEs and initiate a complex series of intracellular signaling resulting in reactive oxygen species generation, inflammation, cellular proliferation, and fibrosis that may possibly exacerbate the damaging effects on cardiac functions in diabetics. AGEs also cause covalent modifications and cross-linking of serum and extracellular matrix proteins; altering their structure, stability, and functions. Early diagnosis of diabetes may prevent its progression to complications and decrease its associated comorbidities. In the present review, we recapitulate the role of AGEs as a crucial mediator of hyperglycemia-mediated detrimental effects in diabetes-associated complications. Furthermore, this review presents an overview of future perspectives for new therapeutic interventions to ameliorate cardiovascular complications in diabetes.
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Affiliation(s)
- Savita Bansal
- Department of Biochemistry, Institute of Home Sciences, University of Delhi, New Delhi 110016, India
| | - Archana Burman
- Department of Biochemistry, Institute of Home Economics, University of Delhi, New Delhi 110016, India
| | - Asok Kumar Tripathi
- Department of Biochemistry, University College of Medical Sciences, University of Delhi, New Delhi 110095, India
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Advanced Glycation End Products (AGEs) and Chronic Kidney Disease: Does the Modern Diet AGE the Kidney? Nutrients 2022; 14:nu14132675. [PMID: 35807857 PMCID: PMC9268915 DOI: 10.3390/nu14132675] [Citation(s) in RCA: 56] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 06/22/2022] [Accepted: 06/23/2022] [Indexed: 12/13/2022] Open
Abstract
Since the 1980s, chronic kidney disease (CKD) affecting all ages has increased by almost 25%. This increase may be partially attributable to lifestyle changes and increased global consumption of a “western” diet, which is typically energy dense, low in fruits and vegetables, and high in animal protein and ultra-processed foods. These modern food trends have led to an increase in the consumption of advanced glycation end products (AGEs) in conjunction with increased metabolic dysfunction, obesity and diabetes, which facilitates production of endogenous AGEs within the body. When in excess, AGEs can be pathological via both receptor-mediated and non-receptor-mediated pathways. The kidney, as a major site for AGE clearance, is particularly vulnerable to AGE-mediated damage and increases in circulating AGEs align with risk of CKD and all-cause mortality. Furthermore, individuals with significant loss of renal function show increased AGE burden, particularly with uraemia, and there is some evidence that AGE lowering via diet or pharmacological inhibition may be beneficial for CKD. This review discusses the pathways that drive AGE formation and regulation within the body. This includes AGE receptor interactions and pathways of AGE-mediated pathology with a focus on the contribution of diet on endogenous AGE production and dietary AGE consumption to these processes. We then analyse the contribution of AGEs to kidney disease, the evidence for dietary AGEs and endogenously produced AGEs in driving pathogenesis in diabetic and non-diabetic kidney disease and the potential for AGE targeted therapies in kidney disease.
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Gregoski MJ, Newton J, Blaylock K, Smith SAO, Turner DP. Examination of the Effectiveness of the Healthy Empowered Active Lifestyles (HEAL) Program on Advanced Glycation End Products. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:4863. [PMID: 34063306 PMCID: PMC8124783 DOI: 10.3390/ijerph18094863] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/11/2021] [Revised: 04/26/2021] [Accepted: 04/28/2021] [Indexed: 11/25/2022]
Abstract
This pilot study investigated the effectiveness of the healthy empowered active lifestyles (HEAL) program to reduce circulatory levels of advanced glycation end products (AGEs) and assess its relationship to BMI, % body fat, fasting glucose, and A1C. The HEAL program was delivered at a local wellness center using a team-based approach and focused on physical activity and dietary education. A sample of twenty primarily European American (19 white, 1 black) participants (i.e., 10 males, 10 females) aged 26 to 71 (m = 48.75 ± 10.26) completed 12 weeks of the HEAL intervention. Pre to post changes in AGEs, BMI, % body fat, fasting glucose, and A1C were examined as primary outcomes. The findings showed participants had the following average reductions: AGEs 36.04 ± 18.48 ug/mL, BMI 2.0 ± 1.2 kg/m2, % body fat 3.18 ± 1.57%, fasting glucose 5.9 ± 17.21 mg/dL, and A1C 0.68 ± 1.11%. All twenty participants successfully completed the entire twelve weeks of the HEAL intervention. The results of this study show that the HEAL intervention provides beneficial reductions of AGEs, BMI, % body fat, fasting glucose, and A1C. In addition, the high adherence shows promise, and demonstrates the potential for HEAL as a behavioral intervention to improve pre-diabetic and other inflammatory related comorbidities. Further replication of results via additional randomized controlled trials is needed.
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Affiliation(s)
- Mathew J. Gregoski
- Department of Public Health Sciences, College of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA
| | - Janis Newton
- Wellness Center, Medical University of South Carolina, Charleston, SC 29425, USA; (J.N.); (K.B.)
| | - Kathleen Blaylock
- Wellness Center, Medical University of South Carolina, Charleston, SC 29425, USA; (J.N.); (K.B.)
| | - Sheila A. O. Smith
- College of Nursing, Medical University of South Carolina, Charleston, SC 29425, USA;
| | - David P. Turner
- Department of Pathology and Laboratory Medicine, College of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA
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Alicic RZ, Cox EJ, Neumiller JJ, Tuttle KR. Incretin drugs in diabetic kidney disease: biological mechanisms and clinical evidence. Nat Rev Nephrol 2021; 17:227-244. [PMID: 33219281 DOI: 10.1038/s41581-020-00367-2] [Citation(s) in RCA: 116] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/16/2020] [Indexed: 01/30/2023]
Abstract
As the prevalence of diabetes continues to climb, the number of individuals living with diabetic complications will reach an unprecedented magnitude. The emergence of new glucose-lowering agents - sodium-glucose cotransporter 2 inhibitors and incretin therapies - has markedly changed the treatment landscape of type 2 diabetes mellitus. In addition to effectively lowering glucose, incretin drugs, which include glucagon-like peptide 1 receptor (GLP1R) agonists and dipeptidyl peptidase 4 (DPP4) inhibitors, can also reduce blood pressure, body weight, the risk of developing or worsening chronic kidney disease and/or atherosclerotic cardiovascular events, and the risk of death. Although kidney disease events have thus far been secondary outcomes in clinical trials, an ongoing phase III trial in patients with diabetic kidney disease will test the effect of a GLP1R agonist on a primary kidney disease outcome. Experimental data have identified the modulation of innate immunity and inflammation as plausible biological mechanisms underpinning the kidney-protective effects of incretin-based agents. These drugs block the mechanisms involved in the pathogenesis of kidney damage, including the activation of resident mononuclear phagocytes, tissue infiltration by non-resident inflammatory cells, and the production of pro-inflammatory cytokines and adhesion molecules. GLP1R agonists and DPP4 inhibitors might also attenuate oxidative stress, fibrosis and cellular apoptosis in the kidney.
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Affiliation(s)
- Radica Z Alicic
- Providence Medical Research Center, Providence Health Care, Spokane, WA, USA.,Department of Medicine, University of Washington School of Medicine, Spokane and Seattle, WA, USA
| | - Emily J Cox
- Providence Medical Research Center, Providence Health Care, Spokane, WA, USA
| | - Joshua J Neumiller
- Department of Pharmacotherapy, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA, USA
| | - Katherine R Tuttle
- Providence Medical Research Center, Providence Health Care, Spokane, WA, USA. .,Nephrology Division, Kidney Research Institute and Institute of Translational Health Sciences, University of Washington, Spokane and Seattle, WA, USA.
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Brinkley TE, Semba RD, Kritchevsky SB, Houston DK, for the Health, Aging, and Body Composition Study. Dietary protein intake and circulating advanced glycation end product/receptor for advanced glycation end product concentrations in the Health, Aging, and Body Composition Study. Am J Clin Nutr 2020; 112:1558-1565. [PMID: 33301008 PMCID: PMC7727487 DOI: 10.1093/ajcn/nqaa241] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Accepted: 08/04/2020] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Advanced glycation end products (AGEs) promote adverse health effects and may contribute to the multi-system functional decline observed in aging. Diet is a major source of AGEs, and foods high in protein may increase circulating AGE concentrations. However, epidemiological evidence that high-protein diets increase AGEs is lacking. OBJECTIVES We examined whether dietary protein intake was associated with serum concentrations of the major AGE carboxymethyl-lysine (CML) and the soluble receptor for AGEs (sRAGE) in 2439 participants from the Health, Aging, and Body Composition study (mean age, 73.6 ± 2.9 y; 52% female; 37% black). METHODS CML and sRAGE were measured by ELISA, and the CML/sRAGE ratio was calculated. Protein intake was estimated using an interviewer-administered FFQ and categorized based on current recommendations for older adults: <0.8 g/kg/d (n = 1077), 0.8 to <1.2 g/kg/d (n = 922), and ≥1.2 g/kg/d (n = 440). Associations between protein intake and AGE-RAGE biomarkers were examined using linear regression models adjusted for demographics, height, lifestyle behaviors, prevalent disease, cognitive function, inflammation, and other dietary factors. RESULTS CML concentrations were higher in individuals with higher total protein intake (adjusted least squares mean ± SE: <0.8 g/kg/d, 829 ± 17 ng/ml; 0.8 to <1.2 g/kg/d, 860 ± 15 ng/ml; ≥1.2 g/kg/d, 919 ± 23 ng/ml; P for trend = 0.001), as were sRAGE concentrations (<0.8 g/kg/d, 1412 ± 34 pg/ml; 0.8 to <1.2 g/kg/d, 1479 ± 31 pg/ml; ≥1.2 g/kg/d, 1574 ± 47 pg/ml; P for trend < 0.0001). Every 0.1 g/kg/d increment in total protein intake was associated with a 13.3 ± 3.0 ng/ml increment in CML and a 22.1 ± 6.0 pg/ml increment in sRAGE (P < 0.0001 for both). Higher CML and sRAGE concentrations were also associated with higher intakes of both animal and vegetable protein (all P values ≤ 0.01). There were no significant associations with the CML/sRAGE ratio. CONCLUSIONS Higher dietary protein intake was associated with higher CML and sRAGE concentrations in older adults; however, the CML/sRAGE ratio remained similar across groups.
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Affiliation(s)
| | - Richard D Semba
- Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Stephen B Kritchevsky
- Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Denise K Houston
- Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA
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Sulforaphane Inhibits MGO-AGE-Mediated Neuroinflammation by Suppressing NF-κB, MAPK, and AGE-RAGE Signaling Pathways in Microglial Cells. Antioxidants (Basel) 2020; 9:antiox9090792. [PMID: 32859007 PMCID: PMC7554773 DOI: 10.3390/antiox9090792] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 08/20/2020] [Accepted: 08/24/2020] [Indexed: 12/26/2022] Open
Abstract
Advanced glycation end products (AGEs) are produced through the binding of glycated protein or lipid with sugar, and they are known to be involved in the pathogenesis of both age-dependent and independent neurological complications. Among dicarbonyl compounds, methylglyoxal (MGO), which is produced from glucose breakdown, is a key precursor of AGE formation and neurotoxicity. Several studies have shown the toxic effects of bovine serum albumin (BSA)-AGE (prepared with glucose, sucrose or fructose) both in in vitro and in vivo. In fact, MGO-derived AGEs (MGO-AGEs) are highly toxic to neurons and other cells of the central nervous system. Therefore, we aimed to investigate the role of MGO-AGEs in microglial activation, a key inflammatory event, or secondary brain damage in neuroinflammatory diseases. Interestingly, we found that sulforaphane (SFN) as a potential candidate to downregulate neuroinflammation induced by MGO-AGEs in BV2 microglial cells. SFN not only inhibited the formation of MGO-AGEs, but it did not show breaking activity on the MGO-mediated AGEs cross-links with protein, indicating that SFN could potentially trap MGO or inhibit toxic AGE damage. In addition, SFN significantly attenuated the production of neuroinflammatory mediators induced by MGO-AGEs in BV2 microglial cells. SFN also lowered the expression levels of AGE receptor (RAGE) in microglial cells, suggesting that SFN could downregulate MGO-AGE-mediated neurotoxicity at the receptor activation level. Altogether, our current study revealed that SFN might show neuropharmacological potential for downregulating MGO-AGEs-mediated neuronal complications thorough attenuating AGE formation and neuroinflammatory responses induced by MGO-AGEs in vitro.
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Sourris KC, Watson A, Jandeleit-Dahm K. Inhibitors of Advanced Glycation End Product (AGE) Formation and Accumulation. Handb Exp Pharmacol 2020; 264:395-423. [PMID: 32809100 DOI: 10.1007/164_2020_391] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
A range of chemically different compounds are known to inhibit the formation and accumulation of advanced glycation end products (AGEs) or disrupt associated signalling pathways. There is evidence that some of these agents can provide end-organ protection in chronic diseases including diabetes. Whilst this group of therapeutics are structurally and functionally different and have a range of mechanisms of action, they ultimately reduce the deleterious actions and the tissue burden of advanced glycation end products. To date it remains unclear if this is due to the reduction in tissue AGE levels per se or the modulation of downstream signal pathways. Some of these agents either stimulate antioxidant defence or reduce the formation of reactive oxygen species (ROS), modify lipid profiles and inhibit inflammation. A number of existing treatments for glucose lowering, hypertension and hyperlipidaemia are also known to reduce AGE formation as a by-product of their action. Targeted AGE formation inhibitors or AGE cross-link breakers have been developed and have shown beneficial effects in animal models of diabetic complications as well as other chronic conditions. However, only a few of these agents have progressed to clinical development. The failure of clinical translation highlights the importance of further investigation of the advanced glycation pathway, the diverse actions of agents which interfere with AGE formation, cross-linking or AGE receptor activation and their effect on the development and progression of chronic diseases including diabetic complications. Advanced glycation end products (AGEs) are (1) proteins or lipids that become glycated as a result of exposure to sugars or (2) non-proteinaceous oxidised lipids. They are implicated in ageing and the development, or worsening, of many degenerative diseases, such as diabetes, atherosclerosis, chronic kidney and Alzheimer's disease. Several antihypertensive and antidiabetic agents and statins also indirectly lower AGEs. Direct AGE inhibitors currently investigated include pyridoxamine and epalrestat, the inhibition of the formation of reactive dicarbonyls such as methylglyoxal as an important precursor of AGEs via increased activation of the detoxifying enzyme Glo-1 and inhibitors of NOX-derived ROS to reduce the AGE/RAGE signalling.
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Affiliation(s)
- Karly C Sourris
- Department of Diabetes, Central Clinical School, Monash University, Melbourne, VIC, Australia
| | - Anna Watson
- Department of Diabetes, Central Clinical School, Monash University, Melbourne, VIC, Australia
| | - Karin Jandeleit-Dahm
- Department of Diabetes, Central Clinical School, Monash University, Melbourne, VIC, Australia.
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Björnson Granqvist A, Ericsson A, Sanchez J, Tonelius P, William-Olsson L, Dahlqvist U, Andersson AK, Tesan Tomic T, Hudkins K, Alpers CE, Pellegrini G, Söderberg M. High-protein diet accelerates diabetes and kidney disease in the BTBR ob/ob mouse. Am J Physiol Renal Physiol 2020; 318:F763-F771. [PMID: 31961715 DOI: 10.1152/ajprenal.00484.2019] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
There is a need for improved animal models that better translate to human kidney disease to predict outcome of pharmacological effects in the patient. The diabetic BTBRob/ob mouse model mimics key features of early diabetic nephropathy in humans, but with chronic injury limited to glomeruli. To explore if we could induce an accelerated and more advanced disease phenotype that closer translates to human disease, we challenged BTBRob/ob mice with a high-protein diet (HPD; 30%) and followed the progression of metabolic and renal changes up to 20 wk of age. Animals on the HPD showed enhanced metabolic derangements, evidenced by further increased levels of glucose, HbA1C, cholesterol, and alanine aminotransferase. The urinary albumin-to-creatinine ratio was markedly increased with a 53-fold change compared with lean controls, whereas BTBRob/ob mice on the standard diet only presented an 8-fold change. HPD resulted in more advanced mesangial expansion already at 14 wk of age compared with BTBRob/ob mice on the standard diet and also aggravated glomerular pathology as well as interstitial fibrosis. Gene expression analysis revealed that HPD triggered expression of markers of fibrosis and inflammation in the kidney and increased oxidative stress markers in urine. This study showed that HPD significantly aggravated renal injury in BTBRob/ob mice by further advancing albuminuria, glomerular, and tubulointerstitial pathology by 20 wk of age. This mouse model offers closer translation to humans and enables exploration of new end points for pharmacological efficacy studies that also holds promise to shorten study length.
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Affiliation(s)
- Anna Björnson Granqvist
- Bioscience, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
| | - Anette Ericsson
- Bioscience, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
| | - José Sanchez
- Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
| | - Pernilla Tonelius
- Bioscience, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
| | - Lena William-Olsson
- Bioscience, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
| | - Ulrika Dahlqvist
- Bioscience, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
| | - Ann-Katrin Andersson
- Bioscience, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
| | - Tajana Tesan Tomic
- Bioscience, Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
| | - Kelly Hudkins
- Department of Pathology, University of Washington, Seattle, Washington
| | - Charles E Alpers
- Department of Pathology, University of Washington, Seattle, Washington
| | - Giovanni Pellegrini
- Pathology, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
| | - Magnus Söderberg
- Pathology, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
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12
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Kramer H. Diet and Chronic Kidney Disease. Adv Nutr 2019; 10:S367-S379. [PMID: 31728497 PMCID: PMC6855949 DOI: 10.1093/advances/nmz011] [Citation(s) in RCA: 82] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Revised: 12/04/2018] [Accepted: 01/07/2019] [Indexed: 02/07/2023] Open
Abstract
Kidney disease affects almost 15% of the US population, and prevalence is anticipated to grow as the population ages and the obesity epidemic continues due to Western dietary practices. The densely caloric Western diet, characterized by high animal protein and low fruit and vegetable content, has fueled the growth of chronic diseases, including chronic kidney disease. The glomerulus or filtering unit of the kidney is very susceptible to barotrauma, and diets high in animal protein impede the glomerulus' ability to protect itself from hemodynamic injury. High animal protein intake combined with low intake of fruits and vegetables also leads to a high net endogenous acid production requiring augmentation of ammonium excretion in order to prevent acidosis. This higher workload of the kidney to maintain a normal serum bicarbonate level may further exacerbate kidney disease progression. This article reviews the potential mechanisms whereby several key characteristics of the typical Western diet may impact kidney disease incidence and progression. Reducing animal protein intake and egg yolk and increasing intake of fruits and vegetables and fiber may prevent or delay end-stage renal disease, but few clinical trials have examined vegetarian diets for management of chronic kidney disease. More research is needed to determine optimal dietary patterns for the prevention of kidney disease and its progression.
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Affiliation(s)
- Holly Kramer
- Department of Public Health Sciences and Medicine
- Division of Nephrology and Hypertension, Loyola University, Chicago, IL
- Address correspondence to HK (e-mail: )
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Endothelial Toxicity of High Glucose and its by-Products in Diabetic Kidney Disease. Toxins (Basel) 2019; 11:toxins11100578. [PMID: 31590361 PMCID: PMC6833015 DOI: 10.3390/toxins11100578] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Revised: 09/26/2019] [Accepted: 10/03/2019] [Indexed: 02/06/2023] Open
Abstract
Alterations of renal endothelial cells play a crucial role in the initiation and progression of diabetic kidney disease. High glucose per se, as well as glucose by-products, induce endothelial dysfunction in both large vessels and the microvasculature. Toxic glucose by-products include advanced glycation end products (AGEs), a group of modified proteins and/or lipids that become glycated after exposure to sugars, and glucose metabolites produced via the polyol pathway. These glucose-related endothelio-toxins notably induce an alteration of the glomerular filtration barrier by increasing the permeability of glomerular endothelial cells, altering endothelial glycocalyx, and finally, inducing endothelial cell apoptosis. The glomerular endothelial dysfunction results in albuminuria. In addition, high glucose and by-products impair the endothelial repair capacities by reducing the number and function of endothelial progenitor cells. In this review, we summarize the mechanisms of renal endothelial toxicity of high glucose/glucose by-products, which encompass changes in synthesis of growth factors like TGF-β and VEGF, induction of oxidative stress and inflammation, and reduction of NO bioavailability. We finally present potential therapies to reduce endothelial dysfunction in diabetic kidney disease.
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Nørgaard SA, Briand F, Sand FW, Galsgaard ED, Søndergaard H, Sørensen DB, Sulpice T. Nephropathy in diabetic db/db mice is accelerated by high protein diet and improved by the SGLT2 inhibitor dapagliflozin. Eur J Pharmacol 2019; 860:172537. [DOI: 10.1016/j.ejphar.2019.172537] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Revised: 07/03/2019] [Accepted: 07/12/2019] [Indexed: 11/29/2022]
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New Insights into the Process of Placentation and the Role of Oxidative Uterine Microenvironment. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2019; 2019:9174521. [PMID: 31341539 PMCID: PMC6615000 DOI: 10.1155/2019/9174521] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Accepted: 05/28/2019] [Indexed: 12/18/2022]
Abstract
For a successful pregnancy to occur, a predecidualized receptive endometrium must be invaded by placental differentiated cells (extravillous trophoblast cells (EVTs)) and, at the same time, continue decidualization. EVT invasion is aimed at anchoring the placenta to the maternal uterus and ensuring local blood supply increase necessary to provide normal placental and foetal development. The first is achieved by migrating through the maternal endometrium and deeper into the myometrium, while the second by transforming uterine spiral arteries into large vessels. This process is a tightly regulated battle comprising interests of both the mother and the foetus. Invading EVTs are required to perform a scope of functions: move, adhere, proliferate, differentiate, interact, and digest the extracellular matrix (ECM); tolerate hypoxia; transform the maternal spiral arteries; and die by apoptosis. All these functions are modulated by their surrounding microenvironment: oxygen, soluble factors (e.g., cytokines, growth factors, and hormones), ECM proteins, and reactive oxygen species. A deeper comprehension of oxidative uterine microenvironment contribution to trophoblast function will be addressed in this review.
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Żebrowska E, Maciejczyk M, Żendzian-Piotrowska M, Zalewska A, Chabowski A. High Protein Diet Induces Oxidative Stress in Rat Cerebral Cortex and Hypothalamus. Int J Mol Sci 2019; 20:ijms20071547. [PMID: 30925663 PMCID: PMC6480352 DOI: 10.3390/ijms20071547] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2019] [Revised: 03/18/2019] [Accepted: 03/26/2019] [Indexed: 12/19/2022] Open
Abstract
This is the first study to analyze the impact of high protein diet (HPD) on antioxidant defense, redox status, as well as oxidative damage on both a local and systemic level. Male Wistar rats were divided into two equal groups (n = 9): HPD (44% protein) and standard diet (CON; 24.2% protein). After eight weeks, glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), superoxide dismutase-1 (SOD-1), reduced glutathione (GSH), uric acid (UA), total antioxidant (TAC)/oxidant status (TOS) as well as advanced glycation end products (AGE), 4-hydroxynonenal (4-HNE), and malondialdehyde (MDA) were analyzed in the serum/plasma, cerebral cortex, and hypothalamus of HPD and CON rats. HPD resulted in higher UA concentration and activity of GPx and CAT in the hypothalamus, whereas in the cerebral cortex these parameters remained unchanged. A significantly lower GSH content was demonstrated in the plasma and hypothalamus of HPD rats when compared to CON rats. Both brain structures expressed higher content of 4-HNE and MDA, whereas AGE was increased only in the hypothalamus of HPD animals. Despite the enhancement in antioxidant defense in the hypothalamus, this mechanism does not protect the hypothalamus from oxidative damage in rats. Hypothalamus is more susceptible to oxidative stress caused by HPD.
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Affiliation(s)
- Ewa Żebrowska
- Department of Physiology, Medical University of Bialystok, 15-089 Bialystok, Poland.
| | - Mateusz Maciejczyk
- Department of Physiology, Medical University of Bialystok, 15-089 Bialystok, Poland.
| | | | - Anna Zalewska
- Department of Restorative Dentistry, Medical University of Bialystok, 15-089 Bialystok, Poland.
| | - Adrian Chabowski
- Department of Physiology, Medical University of Bialystok, 15-089 Bialystok, Poland.
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17
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Krämer AC, Davies MJ. Effect of Methylglyoxal-Induced Glycation on the Composition and Structure of β-Lactoglobulin and α-Lactalbumin. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2019; 67:699-710. [PMID: 30577692 DOI: 10.1021/acs.jafc.8b05809] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
Glycation, and particularly reactions between aldehydes and nucleophiles (thiols, amines), can initiate changes in the structure, solubility, composition, hydrophobicity, conformation, function, and susceptibility to proteolysis of proteins. This can have adverse consequences for mammals, plants, foodstuffs, and pharmaceuticals. Low-molecular-mass dialdehydes such as methylglyoxal (MGO) are much more reactive than parent glucose and therefore potentially highly damaging. These are present at significant levels in some foods. This study investigated whether and how MGO exposure, with or without concurrent heat exposure, affected the major whey proteins β-lactoglobulin and α-lactalbumin. MGO diminished the formation of heat-induced, reducible, intermolecular disulfide cross-links for both proteins, with this being associated, at least in part, with alternative thiol consuming reactions of MGO. At long incubation times, nonreducible protein cross-links were formed in a dose-dependent manner, with LC-MS/MS and UPLC analysis showing the presence of methylglyoxal-lysine dimers (MOLD). UPLC analysis revealed MGO-dependent consumption of specific amino acids in the order Cys > Arg > Lys > Trp for both proteins, with α-lactalbumin affected to a greater extent than β-lactoglobulin. SDS-PAGE revealed altered protein mobility consistent with modification of charged residues. MGO exposure also resulted in increased binding of the hydrophobic dye, 8-anilino-1-naphthalene sulfonic acid, consistent with limited protein unfolding. Overall, these data are consistent with rapid reaction of MGO residues at Cys residues (when available) and surface accessible Arg and Lys residues, with formation of adducts and cross-linked materials. These alternative reactions of dialdehydes diminish direct heat-induced (disulfide) cross-link formation and result in limited protein unfolding.
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Affiliation(s)
- Anna C Krämer
- Department of Biomedical Sciences, Panum Institute , University of Copenhagen , Copenhagen 2200 , Denmark
| | - Michael J Davies
- Department of Biomedical Sciences, Panum Institute , University of Copenhagen , Copenhagen 2200 , Denmark
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18
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Methylglyoxal stress, the glyoxalase system, and diabetic chronic kidney disease. Curr Opin Nephrol Hypertens 2019; 28:26-33. [DOI: 10.1097/mnh.0000000000000465] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Roshankhah S, Salahshoor M, Abdolmaleki A, Jalili C. Can pentoxifylline recover reproductive parameters' damage induced by high-protein diet in male rats? ADVANCES IN HUMAN BIOLOGY 2019. [DOI: 10.4103/aihb.aihb_64_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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20
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Bansal S, Kare PK, Tripathi AK, Madhu SV. Advanced Glycation End Products: A Potential Contributor of Oxidative Stress for Cardio-Vascular Problems in Diabetes. OXIDATIVE STRESS IN HEART DISEASES 2019:437-459. [DOI: 10.1007/978-981-13-8273-4_20] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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21
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Asha Madhavan A, Juneja S, Sen P, Ghosh Moulick R, Bhattacharya J. Gold Nanoparticle-Based Detection of Low Molecular Weight AGEs from In Vitro Glycated Haemoglobin A0 Samples. NANOSCALE RESEARCH LETTERS 2018; 13:390. [PMID: 30511188 PMCID: PMC6277258 DOI: 10.1186/s11671-018-2812-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/18/2018] [Accepted: 11/19/2018] [Indexed: 06/09/2023]
Abstract
Protein glycation is a major biochemical event that takes place in the plasma of diabetic patients due to increased sugar levels. Extensive glycation leads to the formation of advanced glycation end products (AGEs) that is well known for having detrimental effects on diabetic patients. In the current work, we have glycated the physiologically important protein Haemoglobin A0 in vitro to study AGE formation and activity by using them as a template for gold nanoparticle (GNPs) synthesis. It was found that the surface plasmon resonance of synthesised GNPs showed high correlation with the extent of glycation. On fractionation, the glycated Haemoglobin A0 segregated into two distinct population of products, one consisting of proteinaceous, cross-linked larger fragments of Haemoglobin A0 and a second population of non-proteinaceous low molecular weight AGEs. Only low molecular weight AGEs contributed to synthesis of GNPs upon using the fractions as a template, substantiating the principle of proposed GNP-based assay. Owing to its physiological importance, AGEs can be used as a diagnostic means for diabetes and its associated complications. In this study, we have employed the high reactivity of AGEs for the development of a GNP-based novel colorimetric sensor to enable their detection. Our proposed GNP-based sensing could have high clinical significance in detecting diabetes and its associated complexities.
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Affiliation(s)
- A. Asha Madhavan
- School of Biotechnology, Jawaharlal Nehru University, New Mehrauli Road, New Delhi, 110067 India
| | - S. Juneja
- School of Biotechnology, Jawaharlal Nehru University, New Mehrauli Road, New Delhi, 110067 India
| | - P. Sen
- School of Physical Sciences, Jawaharlal Nehru University, New Mehrauli Road, New Delhi, 110067 India
| | - R. Ghosh Moulick
- Amity Institute of Integrative sciences and Health, Amity University Gurgaon, Manesar, Haryana 122413 India
| | - J. Bhattacharya
- School of Biotechnology, Jawaharlal Nehru University, New Mehrauli Road, New Delhi, 110067 India
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22
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Normand G, Lemoine S, Villien M, Le Bars D, Merida I, Irace Z, Troalen T, Costes N, Juillard L. AGE Content of a Protein Load Is Responsible for Renal Performances: A Pilot Study. Diabetes Care 2018; 41:1292-1294. [PMID: 29610272 DOI: 10.2337/dc18-0131] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2018] [Accepted: 03/10/2018] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Chronic kidney disease is associated with higher morbidity and mortality in patients with diabetes. A low-protein diet is recommended to slow diabetic nephropathy progression because each protein load leads to renal hemodynamic variations. The aim of our study was to evaluate whether the advanced glycation end products (AGE) content of a protein load is responsible for the protein-induced renal hemodynamic variations in humans. RESEARCH DESIGN AND METHODS Ten healthy subjects were assigned to a high-protein (1 g/kg) low-AGE (3,000 kU AGE) versus high-AGE (30,000 kU AGE) meal. Renal perfusion, oxygen consumption, and oxygen content were measured before and 120 min after each meal. RESULTS Renal perfusion (3.2 ± 0.5 vs. 3.8 ± 0.4 mL/min/g; P = 0.0002) and oxygen consumption (0.3 ± 0.04 vs. 0.4 ± 0.08 min-1; P = 0.005) increased significantly after the high-AGE meal compared with the low-AGE meal. CONCLUSIONS Our results suggest that the AGE content of a protein load is responsible for renal hemodynamic modifications. Therefore, prevention of diabetic nephropathy progression could aim predominantly at reducing food AGE content.
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Affiliation(s)
- Gabrielle Normand
- Department of Nephrology and Renal Functional Explorations, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France .,CarMeN: Cardiovasculaire, Métabolisme, Diabétologie & Nutrition-INSERM U1060/Lyon 1 University/Institut National de la Recherche Agronomique, Paris, France.,Centre d'Etude et de Recherche Multimodal et Pluridisciplinaire, MR/PET Center, Lyon, France
| | - Sandrine Lemoine
- Department of Nephrology and Renal Functional Explorations, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.,CarMeN: Cardiovasculaire, Métabolisme, Diabétologie & Nutrition-INSERM U1060/Lyon 1 University/Institut National de la Recherche Agronomique, Paris, France.,Centre d'Etude et de Recherche Multimodal et Pluridisciplinaire, MR/PET Center, Lyon, France.,Université Claude Bernard Lyon 1, Lyon, France
| | - Marjorie Villien
- Centre d'Etude et de Recherche Multimodal et Pluridisciplinaire, MR/PET Center, Lyon, France
| | - Didier Le Bars
- Centre d'Etude et de Recherche Multimodal et Pluridisciplinaire, MR/PET Center, Lyon, France.,Université Claude Bernard Lyon 1, Lyon, France
| | - Ines Merida
- Centre d'Etude et de Recherche Multimodal et Pluridisciplinaire, MR/PET Center, Lyon, France
| | - Zacharie Irace
- Centre d'Etude et de Recherche Multimodal et Pluridisciplinaire, MR/PET Center, Lyon, France
| | | | - Nicolas Costes
- Centre d'Etude et de Recherche Multimodal et Pluridisciplinaire, MR/PET Center, Lyon, France
| | - Laurent Juillard
- Department of Nephrology and Renal Functional Explorations, Hôpital Edouard Herriot, Hospices Civils de Lyon, Lyon, France.,CarMeN: Cardiovasculaire, Métabolisme, Diabétologie & Nutrition-INSERM U1060/Lyon 1 University/Institut National de la Recherche Agronomique, Paris, France.,Centre d'Etude et de Recherche Multimodal et Pluridisciplinaire, MR/PET Center, Lyon, France.,Université Claude Bernard Lyon 1, Lyon, France
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Sioson MS, Martindale R, Abayadeera A, Abouchaleh N, Aditianingsih D, Bhurayanontachai R, Chiou WC, Higashibeppu N, Mat Nor MB, Osland E, Palo JE, Ramakrishnan N, Shalabi M, Tam LN, Ern Tan JJ. Nutrition therapy for critically ill patients across the Asia-Pacific and Middle East regions: A consensus statement. Clin Nutr ESPEN 2018; 24:156-164. [PMID: 29576355 DOI: 10.1016/j.clnesp.2017.11.008] [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: 07/27/2017] [Revised: 10/05/2017] [Accepted: 11/28/2017] [Indexed: 12/18/2022]
Abstract
BACKGROUND & AIMS Guidance on managing the nutritional requirements of critically ill patients in the intensive care unit (ICU) has been issued by several international bodies. While these guidelines are consulted in ICUs across the Asia-Pacific and Middle East regions, there is little guidance available that is tailored to the unique healthcare environments and demographics across these regions. Furthermore, the lack of consistent data from randomized controlled clinical trials, reliance on expert consensus, and differing recommendations in international guidelines necessitate further expert guidance on regional best practice when providing nutrition therapy for critically ill patients in ICUs in Asia-Pacific and the Middle East. METHODS The Asia-Pacific and Middle East Working Group on Nutrition in the ICU has identified major areas of uncertainty in clinical practice for healthcare professionals providing nutrition therapy in Asia-Pacific and the Middle East and developed a series of consensus statements to guide nutrition therapy in the ICU in these regions. RESULTS Accordingly, consensus statements have been provided on nutrition risk assessment and parenteral and enteral feeding strategies in the ICU, monitoring adequacy of, and tolerance to, nutrition in the ICU and institutional processes for nutrition therapy in the ICU. Furthermore, the Working Group has noted areas requiring additional research, including the most appropriate use of hypocaloric feeding in the ICU. CONCLUSIONS The objective of the Working Group in formulating these statements is to guide healthcare professionals in practicing appropriate clinical nutrition in the ICU, with a focus on improving quality of care, which will translate into improved patient outcomes.
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Affiliation(s)
- Marianna S Sioson
- Section of Nutrition, Department of Medicine, The Medical City, Pasig, Metro Manila, Philippines.
| | - Robert Martindale
- Division of Gastrointestinal and General Surgery, Oregon Health and Sciences University, Portland, OR, USA
| | - Anuja Abayadeera
- Department of Surgery, Faculty of Medicine, University of Colombo, Colombo, Sri Lanka
| | - Nabil Abouchaleh
- Section of Critical Care Medicine, Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Dita Aditianingsih
- Emergency Intensive Care Unit, Cipto Mangunkusumo Hospital, Jakarta, Indonesia; Department of Anaesthesia and Intensive Care, University of Indonesia, Jakarta, Indonesia
| | - Rungsun Bhurayanontachai
- Division of Critical Care Medicine, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
| | - Wei-Chin Chiou
- Division of Surgical Critical Care, Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan
| | - Naoki Higashibeppu
- Department of Anesthesia and Critical Care, Kobe City Medical Center General Hospital, Kobe, Japan
| | - Mohd Basri Mat Nor
- Kulliyyah of Medicine, International Islamic University Malaysia, Kuala Lumpur, Malaysia
| | - Emma Osland
- Department of Nutrition and Dietetics, Royal Brisbane Hospital, Brisbane, Australia
| | - Jose Emmanuel Palo
- Section of Adult Critical Care, Department of Medicine, The Medical City, Pasig, Metro Manila, Philippines
| | | | - Medhat Shalabi
- Anesthesiology and Intensive Care Department, Alzahra Hospital, Dubai, United Arab Emirates
| | - Luu Ngan Tam
- Clinical Nutrition Department, Cho Ray Hospital, Ho Chi Minh City, Viet Nam
| | - Jonathan Jit Ern Tan
- Department of Anaesthesiology, Intensive Care and Pain Medicine, Tan Tock Seng Hospital, Singapore, Singapore
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24
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Cooke J. Dietary Reduction of Advanced Glycation End Products: An Opportunity for Improved Nutrition Care. J Ren Nutr 2017. [PMID: 28625528 DOI: 10.1053/j.jrn.2017.04.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
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Davis KE, Prasad C, Vijayagopal P, Juma S, Imrhan V. Advanced Glycation End Products, Inflammation, and Chronic Metabolic Diseases: Links in a Chain? Crit Rev Food Sci Nutr 2017; 56:989-98. [PMID: 25259686 DOI: 10.1080/10408398.2012.744738] [Citation(s) in RCA: 62] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Advanced glycation end products (AGEs) are a diverse group of compounds produced when reducing sugars react with proteins or other compounds to form glycosylated molecules. AGEs may form endogenously, and glycation of molecules may negatively affect their function. AGEs may also be consumed in food form with dietary AGEs reported to be particularly high in foods treated with high heat: baked, broiled, grilled, and fried foods. Whether dietary AGEs are absorbed in significant quantities and whether they are harmful if absorbed is a question under current debate. The American Diabetes Association makes no recommendation regarding avoidance of these foods, but many researchers are concerned that they may be pro-inflammatory and way worsen cardiac function, kidney function, diabetes and its complications and may even contribute to obesity.
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Affiliation(s)
- Kathleen E Davis
- a Texas Woman's University, Nutrition and Food Sciences , Denton , Texas , USA
| | - Chandan Prasad
- a Texas Woman's University, Nutrition and Food Sciences , Denton , Texas , USA
| | - Parakat Vijayagopal
- a Texas Woman's University, Nutrition and Food Sciences , Denton , Texas , USA
| | - Shanil Juma
- a Texas Woman's University, Nutrition and Food Sciences , Denton , Texas , USA
| | - Victorine Imrhan
- a Texas Woman's University, Nutrition and Food Sciences , Denton , Texas , USA
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Pereira-Simon S, Rubio GA, Xia X, Cai W, Choi R, Striker GE, Elliot SJ. Inhibition of Advanced Glycation End Products (AGEs) Accumulation by Pyridoxamine Modulates Glomerular and Mesangial Cell Estrogen Receptor α Expression in Aged Female Mice. PLoS One 2016; 11:e0159666. [PMID: 27428057 PMCID: PMC4948910 DOI: 10.1371/journal.pone.0159666] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2016] [Accepted: 07/05/2016] [Indexed: 12/31/2022] Open
Abstract
Age-related increases in oxidant stress (OS) play a role in regulation of estrogen receptor (ER) expression in the kidneys. In this study, we establish that in vivo 17β-estradiol (E2) replacement can no longer upregulate glomerular ER expression by 21 months of age in female mice (anestrous). We hypothesized that advanced glycation end product (AGE) accumulation, an important source of oxidant stress, contributes to these glomerular ER expression alterations. We treated 19-month old ovariectomized female mice with pyridoxamine (Pyr), a potent AGE inhibitor, in the presence or absence of E2 replacement. Glomerular ERα mRNA expression was upregulated in mice treated with both Pyr and E2 replacement and TGFβ mRNA expression decreased compared to controls. Histological sections of kidneys demonstrated decreased type IV collagen deposition in mice receiving Pyr and E2 compared to placebo control mice. In addition, anti-AGE defenses Sirtuin1 (SIRT1) and advanced glycation receptor 1 (AGER1) were also upregulated in glomeruli following treatment with Pyr and E2. Mesangial cells isolated from all groups of mice demonstrated similar ERα, SIRT1, and AGER1 expression changes to those of whole glomeruli. To demonstrate that AGE accumulation contributes to the observed age-related changes in the glomeruli of aged female mice, we treated mesangial cells from young female mice with AGE-BSA and found similar downregulation of ERα, SIRT1, and AGER1 expression. These results suggest that inhibition of intracellular AGE accumulation with pyridoxamine may protect glomeruli against age-related oxidant stress by preventing an increase of TGFβ production and by regulation of the estrogen receptor.
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Affiliation(s)
- Simone Pereira-Simon
- Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida, United States of America
| | - Gustavo A. Rubio
- Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida, United States of America
| | - Xiaomei Xia
- Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida, United States of America
| | - Weijing Cai
- Division of Experimental Diabetes and Aging, Department of Geriatrics and Palliative Care, Mount Sinai School of Medicine, 1 Gustave Levy Place, New York, New York, United States of America
| | - Rhea Choi
- Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, United States of America
| | - Gary E. Striker
- Division of Experimental Diabetes and Aging, Department of Geriatrics and Palliative Care, Mount Sinai School of Medicine, 1 Gustave Levy Place, New York, New York, United States of America
| | - Sharon J. Elliot
- Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida, United States of America
- * E-mail:
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Serra A, Gallart-Palau X, See-Toh RSE, Hemu X, Tam JP, Sze SK. Commercial processed soy-based food product contains glycated and glycoxidated lunasin proteoforms. Sci Rep 2016; 6:26106. [PMID: 27189269 PMCID: PMC4870627 DOI: 10.1038/srep26106] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2015] [Accepted: 04/26/2016] [Indexed: 02/07/2023] Open
Abstract
Nutraceuticals have been proposed to exert positive effects on human health and confer protection against many chronic diseases. A major bioactive component of soy-based foods is lunasin peptide, which has potential to exert a major impact on the health of human consumers worldwide, but the biochemical features of dietary lunasin still remain poorly characterized. In this study, lunasin was purified from a soy-based food product via strong anion exchange solid phase extraction and then subjected to top-down mass spectrometry analysis that revealed in detail the molecular diversity of lunasin in processed soybean foods. We detected multiple glycated proteoforms together with potentially toxic advanced glycation end products (AGEs) derived from lunasin. In both cases, modification sites were Lys24 and Lys29 located at the helical region that shows structural homology with a conserved region of chromatin-binding proteins. The identified post-translational modifications may have an important repercussion on lunasin epigenetic regulatory capacity. Taking together, our results demonstrate the importance of proper chemical characterization of commercial processed food products to assess their impact on consumer's health and risk of chronic diseases.
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Affiliation(s)
- Aida Serra
- School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551 Singapore
| | - Xavier Gallart-Palau
- School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551 Singapore
| | - Rachel Su-En See-Toh
- School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551 Singapore
| | - Xinya Hemu
- School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551 Singapore
| | - James P. Tam
- School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551 Singapore
| | - Siu Kwan Sze
- School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551 Singapore
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28
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Xu R, Yue L, Kang S, Liu L. Assessment of the Concentration of Advanced Glycation End Products in Traditional Chinese Foods. J FOOD PROCESS PRES 2016. [DOI: 10.1111/jfpp.12811] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Affiliation(s)
- Rui Xu
- The College of Food Science; Shenyang Agricultural University; Shenyang 110866 China
| | - Lu Yue
- The College of Food Science; Shenyang Agricultural University; Shenyang 110866 China
| | - Shimo Kang
- The College of Food Science; Shenyang Agricultural University; Shenyang 110866 China
| | - Ling Liu
- The College of Food Science; Shenyang Agricultural University; Shenyang 110866 China
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Golubev RV, Papayan GV, Glazunova AA, Korosteleva NY, Petrishchev NN, Smirnov AV. Examination of skin autofluorescence for the determination of glycation end-products in patients on chronic hemodialysis. TERAPEVT ARKH 2016; 88:65-72. [DOI: 10.17116/terarkh201688665-72] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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Rodríguez-Osorio L, Zambrano DP, Gracia-Iguacel C, Rojas-Rivera J, Ortiz A, Egido J, González Parra E. Use of sevelamer in chronic kidney disease: beyond phosphorus control. Nefrologia 2015; 35:207-17. [PMID: 26300515 DOI: 10.1016/j.nefro.2015.05.022] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2014] [Accepted: 12/10/2014] [Indexed: 12/18/2022] Open
Abstract
Sevelamer is a non-calcium phosphate binder used in advanced chronic kidney disease (CKD) and in dialysis for hyperphosphataemia control. Several experimental, observational studies and clinical trials have shown that sevelamer has pleiotropic effects, beyond hyperphosphataemia control, including actions on inflammation, oxidative stress, lipid profile and atherogenesis, vascular calcification, endothelial dysfunction and the reduction of several uremic toxins. This is the biological basis for its global effect on cardiovascular morbidity and mortality in patients with chronic kidney disease. This review focuses on these pleiotropic actions of sevelamer and their impact on cardiovascular health, with the experience published after more than ten years of clinical expertise.
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Affiliation(s)
| | | | | | | | - Alberto Ortiz
- Servicio de Nefrología. Fundación Jiménez Díaz. Universidad Autónoma de Madrid. Madrid (España)
| | - Jesus Egido
- Servicio de Nefrología. Fundación Jiménez Díaz. Universidad Autónoma de Madrid. Madrid (España)
| | - Emilio González Parra
- Servicio de Nefrología. Fundación Jiménez Díaz. Universidad Autónoma de Madrid. Madrid (España).
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Sijpkens YWJ, Berkhout-Byrne NC, Rabelink TJ. Optimal predialysis care. NDT Plus 2015; 1:iv7-iv13. [PMID: 25983991 PMCID: PMC4421146 DOI: 10.1093/ndtplus/sfn117] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2008] [Accepted: 07/01/2008] [Indexed: 01/18/2023] Open
Abstract
Management of severe chronic kidney disease (CKD) involves dealing with medical, nursing and psychosocial problems and therefore warrants support from a multidisciplinary team. In the Kidney Disease Outcomes Quality Initiative (KDOQI) classification system of CKD, preparation for renal replacement therapy has been recommended in CKD stage 4, characterized by a reduction in the estimated glomerular filtration rate (GFR) of <30 ml/min. In this article we share our approach to perfecting predialysis care. Tools are given to make an estimation of the progression of kidney disease. Also the prevention and treatment of metabolic complications and cardiovascular risk management are summarized. Finally, the possibilities for dialysis but even more important, aiming for pre-emptive transplantation, are being discussed. Using a multidisciplinary integrated care approach predialysis care has come of age.
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Affiliation(s)
- Yvo W J Sijpkens
- Department of Nephrology , Leiden University Medical Center , Leiden , The Netherlands
| | | | - Ton J Rabelink
- Department of Nephrology , Leiden University Medical Center , Leiden , The Netherlands
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32
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Costa EMF, Spritzer PM, Hohl A, Bachega TASS. Effects of endocrine disruptors in the development of the female reproductive tract. ACTA ACUST UNITED AC 2015; 58:153-61. [PMID: 24830592 DOI: 10.1590/0004-2730000003031] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2013] [Accepted: 12/02/2013] [Indexed: 12/13/2022]
Abstract
Environmental agencies have identified a growing number of environmental contaminants that have endocrine disrupting activity, and these can become a major public health problem. It is suggested that endocrine disruptors could account for the higher-than-expected increase in the prevalence of some non-communicable diseases, such as obesity, diabetes, thyroid diseases, and some cancers. Several endocrine Disrupting Chemicals (EDCs), such as pesticides, bisphenol A, phthalates, dioxins, and phytoestrogens, can interact with the female reproductive system and lead to endocrine disruption. Initially, it was assumed that EDCs exert their effects by binding to hormone receptors and transcription factors, but it is currently known that they may also alter the expression of enzymes involved in the synthesis or catabolism of steroids. Biomonitoring studies have identified these compounds in adults, children, pregnant women, and fetuses. Among the diseases of the female reproductive tract associated with EDCs exposure are the following: precocious puberty, polycystic ovary syndrome, and premature ovarian failure. The different populations of the world are exposed to a great number of chemicals through different routes of infection; despite the various available studies, there is still much doubt regarding the additive effect of a mixture of EDCs with similar mechanisms of action.
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Affiliation(s)
- Elaine Maria Frade Costa
- Unidade de Endocrinologia do Desenvolvimento, Laboratório de Hormônios e Genética Molecular LIM42, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP, Brazil
| | - Poli Mara Spritzer
- Divisão de Endocrinologia, Unidade de Ginecologia Endócrina, Hospital de Clínicas de Porto Alegre
| | - Alexandre Hohl
- Serviço de Endocrinologia e Metabologia do Hospital Universitário, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
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33
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Ashraf JM, Arfat MY, Arif Z, Ahmad J, Moinuddin, Alam K. A clinical correlation of anti-DNA-AGE autoantibodies in type 2 diabetes mellitus with disease duration. Cell Immunol 2015; 293:74-9. [PMID: 25577340 DOI: 10.1016/j.cellimm.2014.12.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2014] [Revised: 12/02/2014] [Accepted: 12/23/2014] [Indexed: 11/25/2022]
Abstract
Nonenzymatic glycation of amino groups of DNA bases by reducing sugars can generate advanced glycation end products (AGEs). Cellular formation of AGEs under normal physiology is continuously scanned and removed by efficient system in the cells. However, excess formation and accumulation of AGEs may be cause or consequence of some human diseases. Mammalian DNA incubated with d-glucose for 28 days at 37°C showed structural changes in DNA as confirmed by UV, fluorescence, CD, melting temperature, S1 nuclease sensitivity and gel electrophoresis. Formation of DNA-AGE was confirmed by HPLC and LC-MS. Enzyme immunoassay and electrophoretic mobility shift assay of autoantibodies in type 2 diabetes patients' sera with disease duration of 5-15 years exhibited significantly high binding with DNA-AGE as compared to patients with 1-5 years of disease duration. Autoantibodies against aberrant DNA-AGE may be important in the assessment of initiation/progression of secondary complications in type 2 diabetes mellitus patients.
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Affiliation(s)
- Jalaluddin M Ashraf
- Department of Biochemistry, Faculty of Medicine, A.M.U., Aligarh-202002, UP, India
| | - Mir Yasir Arfat
- Department of Biochemistry, Faculty of Medicine, A.M.U., Aligarh-202002, UP, India
| | - Zarina Arif
- R.G. Centre for Diabetes and Endocrinology, Faculty of Medicine, A.M.U., Aligarh-202002, UP, India
| | - Jamal Ahmad
- R.G. Centre for Diabetes and Endocrinology, Faculty of Medicine, A.M.U., Aligarh-202002, UP, India
| | - Moinuddin
- Department of Biochemistry, Faculty of Medicine, A.M.U., Aligarh-202002, UP, India
| | - Khursheed Alam
- Department of Biochemistry, Faculty of Medicine, A.M.U., Aligarh-202002, UP, India.
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Prasad K, Dhar I. Oxidative stress as a mechanism of added sugar-induced cardiovascular disease. Int J Angiol 2014; 23:217-26. [PMID: 25484552 PMCID: PMC4244242 DOI: 10.1055/s-0034-1387169] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Added sugars comprising of table sugar, brown sugar, corn syrup, maple syrup, honey, molasses, and other sweeteners in the prepared processed foods and beverages have been implicated in the pathophysiology of cardiovascular diseases. This article deals with the reactive oxygen species (ROS) as a mechanism of sugar-induced cardiovascular diseases. There is an association between the consumption of high levels of serum glucose with cardiovascular diseases. Various sources of sugar-induced generation of ROS, including mitochondria, nicotinamide adenine dinucleotide phosphate-oxidase, advanced glycation end products, insulin, and uric acid have been discussed. The mechanism by which ROS induce the development of atherosclerosis, hypertension, peripheral vascular disease, coronary artery disease, cardiomyopathy, heart failure, and cardiac arrhythmias have been discussed in detail. In conclusion, the data suggest that added sugars induce atherosclerosis, hypertension, peripheral vascular disease, coronary artery disease, cardiomyopathy, heart failure, and cardiac arrhythmias and that these effects of added sugars are mediated through ROS.
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Affiliation(s)
- Kailash Prasad
- Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Indu Dhar
- Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
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35
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Rastogi A. Sevelamer revisited: pleiotropic effects on endothelial and cardiovascular risk factors in chronic kidney disease and end-stage renal disease. Ther Adv Cardiovasc Dis 2014; 7:322-42. [PMID: 24327730 PMCID: PMC3917706 DOI: 10.1177/1753944713513061] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Endothelial dysfunction underlies multiple cardiovascular consequences of chronic kidney disease (CKD) and antecedent diabetes or hypertension. Endothelial insults in CKD or end-stage renal disease (ESRD) patients include uremic toxins, serum uric acid, hyperphosphatemia, reactive oxygen species, and advanced glycation endproducts (AGEs). Sevelamer carbonate, a calcium-free intestinally nonabsorbed polymer, is approved for hyperphosphatemic dialysis patients in the US and hyperphosphatemic stage 3-5 CKD patients in many other countries. Sevelamer has been observed investigationally to reduce absorption of AGEs, bacterial toxins, and bile acids, suggesting that it may reduce inflammatory, oxidative, and atherogenic stimuli in addition to its on-label action of lowering serum phosphate. Some studies also suggest that noncalcium binders may contribute less to vascular calcification than calcium-based binders. Exploratory sevelamer carbonate use in patients with stages 2-4 diabetic CKD significantly reduced HbA1c, AGEs, fibroblast growth factor (FGF)-23, and total and low-density lipoprotein (LDL) cholesterol versus calcium carbonate; inflammatory markers decreased and defenses against AGEs increased. Sevelamer has also been observed to reduce circulating FGF-23, potentially reducing risk of left ventricular hypertrophy. Sevelamer but not calcium-based binders in exploratory studies increases flow-mediated vasodilation, a marker of improved endothelial function, in patients with CKD. In contrast, lanthanum carbonate and calcium carbonate effects on FMV did not differ in hemodialysis recipients. The recent independent-CKD randomized trial compared sevelamer versus calcium carbonate in predialysis CKD patients (investigational in the US, on-label in European participants); sevelamer reduced 36-month mortality and the composite endpoint of mortality or dialysis inception. Similarly, independent-HD in incident dialysis patients showed improved survival with 24 months of sevelamer versus calcium-based binders. This review discusses recent exploratory evidence for pleiotropic effects of sevelamer on endothelial function in CKD or ESRD. Endothelial effects of sevelamer may contribute mechanistically to the improved survival observed in some studies of CKD and ESRD patients.
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Affiliation(s)
- Anjay Rastogi
- Division of Nephrology, Department of Medicine, 10630 Santa Monica Boulevard, Los Angeles, CA 90025, USA
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36
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Šebeková K, Simon Klenovics K, Brouder Šebeková K. 26. Advanced glycation end products in infant formulas. HUMAN HEALTH HANDBOOKS 2014. [DOI: 10.3920/978-90-8686-223-8_26] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
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37
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Höhn A, Jung T, Grune T. Pathophysiological importance of aggregated damaged proteins. Free Radic Biol Med 2014; 71:70-89. [PMID: 24632383 DOI: 10.1016/j.freeradbiomed.2014.02.028] [Citation(s) in RCA: 91] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2014] [Revised: 02/28/2014] [Accepted: 02/28/2014] [Indexed: 02/06/2023]
Abstract
Reactive oxygen species (ROS) are formed continuously in the organism even under physiological conditions. If the level of ROS in cells exceeds the cellular defense capacity, components such as RNA/DNA, lipids, and proteins are damaged and modified, thus affecting the functionality of organelles as well. Proteins are especially prominent targets of various modifications such as oxidation, glycation, or conjugation with products of lipid peroxidation, leading to the alteration of their biological function, nonspecific interactions, and the production of high-molecular-weight protein aggregates. To ensure the maintenance of cellular functions, two proteolytic systems are responsible for the removal of oxidized and modified proteins, especially the proteasome and organelles, mainly the autophagy-lysosomal systems. Furthermore, increased protein oxidation and oxidation-dependent impairment of proteolytic systems lead to an accumulation of oxidized proteins and finally to the formation of nondegradable protein aggregates. Accordingly, the cellular homeostasis cannot be maintained and the cellular metabolism is negatively affected. Here we address the current knowledge of protein aggregation during oxidative stress, aging, and disease.
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Affiliation(s)
- Annika Höhn
- Department of Nutritional Toxicology, Institute of Nutrition, Friedrich-Schiller-University Jena, 07743 Jena, Germany
| | - Tobias Jung
- Department of Nutritional Toxicology, Institute of Nutrition, Friedrich-Schiller-University Jena, 07743 Jena, Germany
| | - Tilman Grune
- Department of Nutritional Toxicology, Institute of Nutrition, Friedrich-Schiller-University Jena, 07743 Jena, Germany.
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38
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Increased protein aggregation in Zucker diabetic fatty rat brain: identification of key mechanistic targets and the therapeutic application of hydrogen sulfide. BMC Cell Biol 2014; 15:1. [PMID: 24393531 PMCID: PMC3998068 DOI: 10.1186/1471-2121-15-1] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2013] [Accepted: 12/23/2013] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Diabetes and particularly high blood glucose levels are implicated in neurodegeneration. One of the hallmarks of neurodegeneration is protein aggregation. We investigated the presence of protein aggregation in the frontal brain of Zucker diabetic fatty (ZDF) rats, an animal model for diabetes. Further, the effect of NaHS in suppressing protein aggregation in cultured brain slices from ZDF was assessed. RESULTS The levels of protein synthesis, protein/gene expression, autophagy and anti-oxidant defense were evaluated in ZDF and control (Lean) brains.Compared to Lean, ZDF brains displayed a significant increase in protein aggregates, p-tau, fibronectin expression and protein glycosylation. Increased phosphorylation of mTOR and S6 ribosomal protein in ZDF indicated higher protein synthesis, while the increase in ubiquitinated proteins and LC3-I in ZDF brains accompanied by lower LC3-II expression and LC3-II/LC3-I levels indicated the blockage of proteolytic pathways. CBS (cystathionine beta synthase) protein and mRNA expression and thiol group levels in ZDF brains were lower compared to Lean. ZDF brains show a higher level of reactive oxygen species. In vitro NaHS treatment normalized proteostasis while counteracting oxidative stress. CONCLUSION Our data demonstrate increased protein synthesis and aggregation in the diabetic ZDF rat brain, which was reversible by NaHS treatment.This is the first report on the potential use of NaHS as a novel strategy against protein aggregation in diabetic brain.
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39
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Nguyen HT, van der Fels-Klerx HJ, van Boekel MAJS. Nϵ-(carboxymethyl)lysine: A Review on Analytical Methods, Formation, and Occurrence in Processed Food, and Health Impact. FOOD REVIEWS INTERNATIONAL 2013. [DOI: 10.1080/87559129.2013.853774] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
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Huang JH, Cheng FC, Tsai LC, Lee NY, Lu YF. Appropriate physical activity and dietary intake achieve optimal metabolic control in older type 2 diabetes patients. J Diabetes Investig 2013; 5:418-27. [PMID: 25411601 PMCID: PMC4210067 DOI: 10.1111/jdi.12164] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2013] [Revised: 08/29/2013] [Accepted: 09/01/2013] [Indexed: 11/30/2022] Open
Abstract
Aims/Introduction The aim of the present study was to investigate an appropriate level of physical activity and optimal dietary intake in older type 2 diabetes patients. Materials and Methods The cross‐sectional study enrolled 210 older type 2 diabetes patients. Participants were interviewed to obtain information on physical activity, 24‐h dietary recall and typical weekly dietary patterns. Anthropometric measurements, and biochemical analysis of blood and urine were determined. Results Moderate physical activity (either moderate leisure‐time physical activity or moderate physical activity level) and diet with protein intake of ≥0.8 g/kg/day were associated with lower glycated hemoglobin and triglyceride, higher high‐density lipoprotein, lower waist circumference, body mass index and body fat, as well as better serum magnesium and albumin levels in older diabetic patients. In contrast, inadequate protein intake was correlated with higher glycated hemoglobin, triglyceride, body fat percentage, waist circumference and body mass index. In addition, high physical activity with inadequate protein and magnesium intake might exacerbate magnesium deficiency, resulting in poor glycemic control in older diabetic patients. Furthermore, low physical activity and inadequate protein intake were linked with poor glycemic control, and lower high‐density lipoprotein, and higher triglyceride, body fat percentage, waist circumference and body mass index. Conclusions Moderate physical activity and adequate dietary protein intake (≥0.8 g/kg/day) might be the optimal recommendation for better metabolic control in older adults with type 2 diabetes.
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Affiliation(s)
- Jui-Hua Huang
- PhD Program in Nutrition and Food Science and Department of Nutritional Science Fu-Jen Catholic University Hsinchuang New Taipei City Taiwan
| | - Fu-Chou Cheng
- Stem Cell Center Department of Medical Research Taichung Veterans General Hospital Taichung Taiwan
| | - Leih-Ching Tsai
- Division of Endocrine and Metabolism Department of Internal Medicine Erlin-Branch Changhua Christian Hospital Changhua Taiwan
| | - Ning-Yuean Lee
- College of Living Technology Tainan University of Technology Tainan Taiwan
| | - Yi-Fa Lu
- PhD Program in Nutrition and Food Science and Department of Nutritional Science Fu-Jen Catholic University Hsinchuang New Taipei City Taiwan
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41
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Guedes-Martins L, Matos L, Soares A, Silva E, Almeida H. AGEs, contributors to placental bed vascular changes leading to preeclampsia. Free Radic Res 2013; 47 Suppl 1:70-80. [PMID: 23796030 DOI: 10.3109/10715762.2013.815347] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Glycation of proteins or other biomolecules and their further long-term degradation result in the formation of advanced glycation end products, AGEs. AGEs and other ligands interact with their receptors, RAGEs, localized to a variety of tissues, but mainly in endothelium and vascular wall cells. This interaction triggers diverse signaling pathways that converge on the activation of NF-κB and the initiation of a local inflammatory reaction that, when prolonged, results in dysfunctional features. Preeclampsia is a serious vascular disorder centred at the placenta-uterine interface, the placental bed, but the condition extends to the mother's circulation. RAGEs have notorious expression in the placental bed tissues along pregnancy but, in addition, RAGEs and their ligands are expressed in the fetal membranes and are found in the amniotic fluid and the mother's serum. Disorders complicating pregnancies and having an important vascular involvement, as preeclampsia and diabetes mellitus, have additional enhanced AGE/RAGE expression variation. This indicates that for their assessment, the assay of RAGEs or their ligands may become useful diagnostic or prognostic procedures.
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Affiliation(s)
- L Guedes-Martins
- Departamento de Biologia Experimental, Faculdade de Medicina da Universidade do Porto, Porto, Portugal
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42
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Kumar PA, Chitra PS, Reddy GB. Metabolic syndrome and associated chronic kidney diseases: nutritional interventions. Rev Endocr Metab Disord 2013; 14:273-286. [PMID: 24036690 DOI: 10.1007/s11154-013-9268-2] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Lifestyle changes such as dietary habits, sedentary life and consumption of energy-dense foods that have occurred over the years has led to an epidemic of abdominal obesity, which in turn resulted in dramatic increase in the prevalence of metabolic syndrome (MetS). Different expert panels have provided various definitions for MetS to enable a clinical diagnosis and treatment of patients at risk of associated complications. Obesity and obesity mediated MetS has been paralleled by escalation in the incidence of chronic kidney disease (CKD). A better understanding of the pathophysiology of MetS and identification of individuals with MetS early in the life course could be important for initiating interventions such as lifestyle modification and dietary restrictions that form the basis for prevention and treatment of MetS and related co-morbidities including CKD. This review is intended to provide a comprehensive summary of the evolution of definition of MetS and association of MetS with CKD. In particular, mechanism of obesity and diabetes mediated CKD and emerging dietary therapies for MetS associated CKD will be discussed.
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Affiliation(s)
- P Anil Kumar
- Department of Biochemistry, National Institute of Nutrition, Hyderabad, 500007, India,
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43
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Meek RL, LeBoeuf RC, Saha SA, Alpers CE, Hudkins KL, Cooney SK, Anderberg RJ, Tuttle KR. Glomerular cell death and inflammation with high-protein diet and diabetes. Nephrol Dial Transplant 2013; 28:1711-20. [PMID: 23314315 DOI: 10.1093/ndt/gfs579] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Overfeeding amino acids (AAs) increases cellular exposure to advanced glycation end-products (AGEs), a mechanism for protein intake to worsen diabetic kidney disease (DKD). This study assessed receptor for AGE (RAGE)-mediated apoptosis and inflammation in glomerular cells exposed to metabolic stressors characteristic of high-protein diets and/or diabetes in vitro with proof-of-concept appraisal in vivo. METHODS Mouse podocytes and mesangial cells were cultured under control and metabolic stressor conditions: (i) no addition; (ii) increased AAs (4-6-fold>control); (iii) high glucose (HG, 30.5 mM); (iv) AA/HG combination; (v) AGE-bovine serum albumin (AGE-BSA, 300 µg/mL); (vi) BSA (300 µg/mL). RAGE was inhibited by blocking antibody. Diabetic (streptozotocin) and nondiabetic mice (C57BL/6J) consumed diets with protein calories of 20 or 40% (high) for 20 weeks. People with DKD and controls provided 24-h urine samples. RESULTS In podocytes and mesangial cells, apoptosis (caspase 3/7 activity and TUNEL) increased in all metabolic stressor conditions. Both inflammatory mediator expression (real-time reverse transcriptase-polymerase chain reaction: serum amyloid A, caspase-4, inducible nitric oxide synthase, and monocyte chemotactic protein-1) and RAGE (immunostaining) also increased. RAGE inhibition prevented apoptosis and inflammation in podocytes. Among mice fed high protein, podocyte number (WT-1 immunostaining) decreased in the diabetic group, and only these diabetic mice developed albuminuria. Protein intake (urea nitrogen) correlated with AGE excretion (carboxymethyllysine) in people with DKD and controls. CONCLUSIONS High-protein diet and/or diabetes-like conditions increased glomerular cell death and inflammation, responses mediated by RAGEs in podocytes. The concept that high-protein diets exacerbate early indicators of DKD is supported by data from mice and people.
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Affiliation(s)
- Rick L Meek
- Providence Medical Research Center, Providence Sacred Heart Medical Center, Spokane, WA, USA.
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44
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McGillicuddy FC, Roche HM. Nutritional status, genetic susceptibility, and insulin resistance--important precedents to atherosclerosis. Mol Nutr Food Res 2012; 56:1173-84. [PMID: 22760984 DOI: 10.1002/mnfr.201100785] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Atherosclerosis is a progressive disease that starts early in life and is manifested clinically as coronary artery disease (CAD), cerebrovascular disease, or peripheral artery disease. CAD remains the leading cause of morbidity and mortality in Western society despite the great advances made in understanding its underlying pathophysiology. The key risk factors associated with CAD include hypercholesterolemia, hypertension, poor diet, obesity, age, male gender, smoking, and physical inactivity. Genetics also play an important role that may interact with environmental factors, including diet, nutritional status, and physiological parameters. Furthermore, certain chronic inflammatory conditions also predispose to the development of CAD. The spiraling increase in obesity rates worldwide has made it more pertinent than ever before to understand the metabolic perturbations that link over nutrition to enhanced cardiovascular risk. Great breakthroughs have been made at the pharmacological level to manage CAD; statins and aspirin have revolutionized treatment of CAD and prolonged lifespan. Nonetheless, lifestyle intervention prior to clinical presentation of CAD symptoms would negate/delay the need for chronic pharmacotherapy in at-risk individuals which in turn would relieve healthcare systems of a costly burden. Throughout this review, we debate the relative impact of nutrition versus genetics in driving CAD. We will investigate how overnutrition affects adipose tissue biology and drives IR and will discuss the subsequent implications for the cardiovascular system. Furthermore, we will discuss how lifestyle interventions including diet modification and weight loss can improve both IR and metabolic dyslipidemia that is associated with obesity. We will conclude by delving into the concept that nutritional status interacts with genetic susceptibility, such that perhaps a more personalized nutrition approach may be more effective in determining diet-related risk as well as response to nutritional interventions.
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Affiliation(s)
- Fiona C McGillicuddy
- UCD Conway Institute, School of Public Health & Population Science, University College Dublin, Dublin, Ireland
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Billaud M, Johnstone SR, Isakson BE. Loss of Compliance in Small Arteries, but Not in Conduit Arteries, After 6 Weeks Exposure to High Fat Diet. J Cardiovasc Transl Res 2012; 5:256-63. [DOI: 10.1007/s12265-012-9354-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2011] [Accepted: 02/16/2012] [Indexed: 10/28/2022]
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Tuttle KR, Milton JE, Packard DP, Shuler LA, Short RA. Dietary amino acids and blood pressure: a cohort study of patients with cardiovascular disease. Am J Kidney Dis 2012; 59:803-9. [PMID: 22381643 DOI: 10.1053/j.ajkd.2011.12.026] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2011] [Accepted: 12/22/2011] [Indexed: 01/12/2023]
Abstract
BACKGROUND Dietary protein has been variably reported to either lower or raise blood pressure. The purpose of this study was to determine whether intakes of specific amino acids differentially associate with blood pressure. STUDY DESIGN Observational cohort study by secondary analysis of clinical trial data. SETTING & PARTICIPANTS Study of low-fat versus Mediterranean-style diets in patients with prevalent cardiovascular disease. PREDICTOR Dietary amino acids. OUTCOMES Systolic and diastolic blood pressure. MEASUREMENTS Dietary nutrients and cardiovascular risk factors were assessed at baseline, 3 and 6 months, and then every 6 months for 2 years. RESULTS Baseline blood pressure was 119 ± 16 (SD)/72 ± 10 (SD) mm Hg (n = 92) and dietary protein intake was 80 ± 31 g/d. Independent amino acid variables (quartiles of intake) were analyzed by generalized estimating equation models with prespecified covariates for time-varying systolic and diastolic blood pressure. The odds of each 1-SD higher systolic or diastolic blood pressure (ie, 16 and 10 mm Hg, respectively) were increased per quartile of intake for methionine (ORs of 1.29 [95% CI, 1.14-1.46] and 1.21 [95% CI, 1.05-1.39], respectively) and alanine (ORs of 1.17 [95% CI, 1.05-1.30] and 1.22 [95% CI, 1.07-1.38], respectively). Quartiles of intake for threonine (ORs of 0.84 [95% CI, 0.74-0.96] and 0.87 [95% CI, 0.75-1.01], respectively) and histidine (ORs of 0.92 [95% CI, 0.86-1.00] and 0.89 [95% CI, 0.82-0.97], respectively) had inverse associations with the same degree of difference in blood pressure. LIMITATIONS Modest sample-size biases toward the chance of false-negative results; potential for residual confounding; colinearity between amino acids may obscure relevant relationships to blood pressure; associational findings do not establish causality. CONCLUSIONS Intakes of methionine and alanine were associated positively with higher blood pressure, whereas intakes of threonine and histidine had inverse associations. These amino acids merit further study for advancing dietary approaches to blood pressure reduction.
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Affiliation(s)
- Katherine R Tuttle
- Providence Medical Research Center, Providence Sacred Heart Medical Center, Spokane, WA 99204, USA.
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Abstract
It is well established that obesity is a risk factor for the development of chronic kidney disease (CKD) and may promote the progression to end stage renal disease (ESRD). Therefore, it is strongly suggested that reduction of body weight can be an important intervention in order to reduce the prevalence of renal impairment. The current article describes extensively the already published trials which have studied the association between weight loss and kidney disease. The weight management programs include surgical and non-surgical interventions (low-calorie diet, aerobic exercise, drug-induced weight loss, combination treatment). The focus has been placed on the following renal function markers: albuminuria, proteinuria, glomerular filtration rate (GFR), and creatinine clearance. This review also aims to clarify challenges that clinicians have to deal with in everyday practice regarding the management of obesity-induced kidney disease (degree of weight loss, duration of the weight loss program, early initiation of the intervention).
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Abstract
Any evaluation of steroids in kidney transplantation is hampered by individual variability in metabolism, the lack of clinically available steroid blood levels, and overall little attention to steroid exposure. Many feel that steroids were an essential part of chronic immunosuppression in past decades but may no longer be necessary in low-risk populations when our newer and more potent drugs are used. Potential differences in long-term outcome will be unapparent in short-term antibody induction studies in low-risk patients, particularly with low on steroid doses, as may have happened in the recent, well-done Astellas trial. In many studies, the evidence for the superiority of mycophenolate (MMF) and tacrolimus (TAC) was not as strong as the evidence for the benefit of steroids in the Canadian cyclosporine study. As the practice of steroid withdrawal has increased, we have not seen the improvement in long-term graft survival that many expected with our newer agents. Steroids have immunosuppressive effects even in doses that are low by historic standards, and side effects may not justify their abandonment.
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Luevano-Contreras C, Chapman-Novakofski K. Dietary advanced glycation end products and aging. Nutrients 2010; 2:1247-65. [PMID: 22254007 PMCID: PMC3257625 DOI: 10.3390/nu2121247] [Citation(s) in RCA: 264] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2010] [Revised: 11/30/2010] [Accepted: 12/10/2010] [Indexed: 02/06/2023] Open
Abstract
Advanced glycation end products (AGEs) are a heterogeneous, complex group of compounds that are formed when reducing sugar reacts in a non-enzymatic way with amino acids in proteins and other macromolecules. This occurs both exogenously (in food) and endogenously (in humans) with greater concentrations found in older adults. While higher AGEs occur in both healthy older adults and those with chronic diseases, research is progressing to both quantify AGEs in food and in people, and to identify mechanisms that would explain why some human tissues are damaged, and others are not. In the last twenty years, there has been increased evidence that AGEs could be implicated in the development of chronic degenerative diseases of aging, such as cardiovascular disease, Alzheimer’s disease and with complications of diabetes mellitus. Results of several studies in animal models and humans show that the restriction of dietary AGEs has positive effects on wound healing, insulin resistance and cardiovascular diseases. Recently, the effect of restriction in AGEs intake has been reported to increase the lifespan in animal models. This paper will summarize the work that has been published for both food AGEs and in vivo AGEs and their relation with aging, as well as provide suggestions for future research.
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Affiliation(s)
- Claudia Luevano-Contreras
- Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
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Abstract
The effect of sugars on aging skin is governed by the simple act of covalently cross-linking two collagen fibers, which renders both of them incapable of easy repair. Glucose and fructose link the amino acids present in the collagen and elastin that support the dermis, producing advanced glycation end products or "AGEs." This process is accelerated in all body tissues when sugar is elevated and is further stimulated by ultraviolet light in the skin. The effect on vascular, renal, retinal, coronary, and cutaneous tissues is being defined, as are methods of reducing the glycation load through careful diet and use of supplements.
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