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Côco LZ, Aires R, Carvalho GR, Belisário EDS, Yap MKK, Amorim FG, Conde-Aranda J, Nogueira BV, Vasquez EC, Pereira TDMC, Campagnaro BP. Unravelling the Gastroprotective Potential of Kefir: Exploring Antioxidant Effects in Preventing Gastric Ulcers. Cells 2023; 12:2799. [PMID: 38132119 PMCID: PMC10742242 DOI: 10.3390/cells12242799] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 11/28/2023] [Accepted: 12/05/2023] [Indexed: 12/23/2023] Open
Abstract
The present study was conducted to evaluate the protective effect of milk kefir against NSAID-induced gastric ulcers. Male Swiss mice were divided into three groups: control (Vehicle; UHT milk at a dose of 0.3 mL/100 g), proton pump inhibitor (PPI; lansoprazole 30 mg/kg), and 4% milk kefir (Kefir; 0.3 mL/100 g). After 14 days of treatment, gastric ulcer was induced by oral administration of indomethacin (40 mg/kg). Reactive oxygen species (ROS), nitric oxide (NO), DNA content, cellular apoptosis, IL-10 and TNF-α levels, and myeloperoxidase (MPO) enzyme activity were determined. The interaction networks between NADPH oxidase 2 and kefir peptides 1-35 were determined using the Residue Interaction Network Generator (RING) webserver. Pretreatment with kefir for 14 days prevented gastric lesions. In addition, kefir administration reduced ROS production, DNA fragmentation, apoptosis, and TNF-α systemic levels. Simultaneously, kefir increased NO bioavailability in gastric cells and IL-10 systemic levels. A total of 35 kefir peptides showed affinity with NADPH oxidase 2. These findings suggest that the gastroprotective effect of kefir is due to its antioxidant and anti-inflammatory properties. Kefir could be a promising natural therapy for gastric ulcers, opening new perspectives for future research.
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Affiliation(s)
- Larissa Zambom Côco
- Laboratory of Translational Physiology and Pharmacology, Pharmaceutical Sciences Graduate Program, Vila Velha University (UVV), Vila Velha 29102-920, ES, Brazil; (L.Z.C.); (R.A.); (G.R.C.); (E.d.S.B.); (E.C.V.); (T.d.M.C.P.)
| | - Rafaela Aires
- Laboratory of Translational Physiology and Pharmacology, Pharmaceutical Sciences Graduate Program, Vila Velha University (UVV), Vila Velha 29102-920, ES, Brazil; (L.Z.C.); (R.A.); (G.R.C.); (E.d.S.B.); (E.C.V.); (T.d.M.C.P.)
| | - Glaucimeire Rocha Carvalho
- Laboratory of Translational Physiology and Pharmacology, Pharmaceutical Sciences Graduate Program, Vila Velha University (UVV), Vila Velha 29102-920, ES, Brazil; (L.Z.C.); (R.A.); (G.R.C.); (E.d.S.B.); (E.C.V.); (T.d.M.C.P.)
| | - Eduarda de Souza Belisário
- Laboratory of Translational Physiology and Pharmacology, Pharmaceutical Sciences Graduate Program, Vila Velha University (UVV), Vila Velha 29102-920, ES, Brazil; (L.Z.C.); (R.A.); (G.R.C.); (E.d.S.B.); (E.C.V.); (T.d.M.C.P.)
| | | | - Fernanda Gobbi Amorim
- Laboratory of Mass Spectrometry, Department of Chemistry, University of Liège, 4000 Liège, Belgium;
| | - Javier Conde-Aranda
- Molecular and Cellular Gastroenterology, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain;
| | - Breno Valentim Nogueira
- Department of Morphology, Health Sciences Center, Federal University of Espírito Santo (UFES), Vitoria 29047-105, ES, Brazil;
| | - Elisardo Corral Vasquez
- Laboratory of Translational Physiology and Pharmacology, Pharmaceutical Sciences Graduate Program, Vila Velha University (UVV), Vila Velha 29102-920, ES, Brazil; (L.Z.C.); (R.A.); (G.R.C.); (E.d.S.B.); (E.C.V.); (T.d.M.C.P.)
| | - Thiago de Melo Costa Pereira
- Laboratory of Translational Physiology and Pharmacology, Pharmaceutical Sciences Graduate Program, Vila Velha University (UVV), Vila Velha 29102-920, ES, Brazil; (L.Z.C.); (R.A.); (G.R.C.); (E.d.S.B.); (E.C.V.); (T.d.M.C.P.)
| | - Bianca Prandi Campagnaro
- Laboratory of Translational Physiology and Pharmacology, Pharmaceutical Sciences Graduate Program, Vila Velha University (UVV), Vila Velha 29102-920, ES, Brazil; (L.Z.C.); (R.A.); (G.R.C.); (E.d.S.B.); (E.C.V.); (T.d.M.C.P.)
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MIYOSHI MAKOTO, USAMI MAKOTO, KAJITA AYUMI, KAI MOTOKI, NISHIYAMA YUYA, SHINOHARA MASAKAZU. Effect of Oral Tributyrin Treatment on Lipid Mediator Profiles in Endotoxin-Induced Hepatic Injury. THE KOBE JOURNAL OF MEDICAL SCIENCES 2020; 66:E129-E138. [PMID: 33994516 PMCID: PMC8212808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Accepted: 10/21/2020] [Indexed: 06/12/2023]
Abstract
Eicosanoid modulation by butyrate has been reported in various cells and conditions. Recently, comprehensive analyses of lipid mediators using liquid chromatography/tandem mass spectrometry has been reported. We hypothesized that tributyrin, a prodrug of butyrate, may attenuate LPS-induced liver injury in rats by suppressing the production of pro-inflammatory lipid mediators and/or by inducing anti-inflammatory specialized proresolving mediators. To test this, groups of Wistar rats were orally administered tributyrin (1 g/kg body weight) or vehicle 1 h before intraperitoneal injection of LPS. The livers were collected at 0, 1.5, 6, and 24 h later and analyzed: lipid mediators were profiled by liquid chromatography/tandem mass spectrometry; expression of cyclooxygenase-2, 5-lipoxygenase (LOX), 12/15-LOX, and leukotriene (LT) A4 hydrolase, and nuclear translocation of 5-LOX were evaluated by western blot analysis; and induction of liver injury was assessed by immunostaining for 8-hydroxy-2'-deoxyguanosine, an indicator of oxidative DNA damage. We found that tributyrin treatment attenuated LPS-induced production of pro-inflammatory LTB4 (p < 0.05) and decreased oxidative stress levels in the liver. Tributyrin also attenuated the nuclear translocation of 5-LOX in response to LPS, suggesting a possible mechanism for the LTB4 reduction. LPS-induced changes in other lipid mediators were not significantly affected by tributyrin treatment up to 24 h after LPS injection. Our results suggest that oral tributyrin administration protects against endotoxemia-associated liver damage by reducing production of the pro-inflammatory eicosanoid LTB4.
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Affiliation(s)
- MAKOTO MIYOSHI
- Department of Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Japan
| | - MAKOTO USAMI
- Faculty of Clinical Nutrition and Dietetics, Konan Women’s University, Kobe, Japan
| | - AYUMI KAJITA
- Department of Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Japan
| | - MOTOKI KAI
- Department of Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Japan
| | - YUYA NISHIYAMA
- Department of Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Japan
| | - MASAKAZU SHINOHARA
- The Integrated Center for Mass Spectrometry, Kobe University Graduate School of Medicine, Kobe, Japan
- Division of Epidemiology, Kobe University Graduate School of Medicine, Kobe, Japan
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Tham EH, Rajakulendran M, Lee BW, Van Bever HPS. Epicutaneous sensitization to food allergens in atopic dermatitis: What do we know? Pediatr Allergy Immunol 2020; 31:7-18. [PMID: 31541586 DOI: 10.1111/pai.13127] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Revised: 08/05/2019] [Accepted: 09/12/2019] [Indexed: 02/06/2023]
Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disease mainly affecting children, which has no definitive curative therapy apart from natural outgrowing. AD is persistent in 30%-40% of children. Epithelial barrier dysfunction in AD is a significant risk factor for the development of epicutaneous food sensitization, food allergy, and other allergic disorders. There is evidence that prophylactic emollient applications from birth may be useful for primary prevention of AD, but biomarkers are needed to guide cost-effective targeted therapy for high-risk individuals. In established early-onset AD, secondary preventive strategies are needed to attenuate progression to other allergic disorders such as food allergy, asthma, and allergic rhinitis (the atopic march). This review aims to describe the mechanisms underpinning the development of epicutaneous sensitization to food allergens and progression to clinical food allergy; summarize current evidence for interventions to halt the progression from AD to food sensitization and clinical food allergy; and highlight unmet needs and directions for future research.
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Affiliation(s)
- Elizabeth Huiwen Tham
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.,Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System, Singapore, Singapore
| | - Mohana Rajakulendran
- Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System, Singapore, Singapore
| | - Bee Wah Lee
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Hugo P S Van Bever
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.,Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System, Singapore, Singapore
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Effects of Intestinal Microbial⁻Elaborated Butyrate on Oncogenic Signaling Pathways. Nutrients 2019; 11:nu11051026. [PMID: 31067776 PMCID: PMC6566851 DOI: 10.3390/nu11051026] [Citation(s) in RCA: 115] [Impact Index Per Article: 19.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Revised: 04/29/2019] [Accepted: 05/05/2019] [Indexed: 12/12/2022] Open
Abstract
The intestinal microbiota is well known to have multiple benefits on human health, including cancer prevention and treatment. The effects are partially mediated by microbiota-produced short chain fatty acids (SCFAs) such as butyrate, propionate and acetate. The anti-cancer effect of butyrate has been demonstrated in cancer cell cultures and animal models of cancer. Butyrate, as a signaling molecule, has effects on multiple signaling pathways. The most studied effect is its inhibition on histone deacetylase (HDAC), which leads to alterations of several important oncogenic signaling pathways such as JAK2/STAT3, VEGF. Butyrate can interfere with both mitochondrial apoptotic and extrinsic apoptotic pathways. In addition, butyrate also reduces gut inflammation by promoting T-regulatory cell differentiation with decreased activities of the NF-κB and STAT3 pathways. Through PKC and Wnt pathways, butyrate increases cancer cell differentiation. Furthermore, butyrate regulates oncogenic signaling molecules through microRNAs and methylation. Therefore, butyrate has the potential to be incorporated into cancer prevention and treatment regimens. In this review we summarize recent progress in butyrate research and discuss the future development of butyrate as an anti-cancer agent with emphasis on its effects on oncogenic signaling pathways. The low bioavailability of butyrate is a problem, which precludes clinical application. The disadvantage of butyrate for medicinal applications may be overcome by several approaches including nano-delivery, analogue development and combination use with other anti-cancer agents or phytochemicals.
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Kaur A, Chen T, Green SJ, Mutlu E, Martin BR, Rumpagaporn P, Patterson JA, Keshavarzian A, Hamaker BR. Physical Inaccessibility of a Resistant Starch Shifts Mouse Gut Microbiota to Butyrogenic Firmicutes. Mol Nutr Food Res 2019; 63:e1801012. [PMID: 30659764 DOI: 10.1002/mnfr.201801012] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2018] [Revised: 01/03/2019] [Indexed: 12/14/2022]
Affiliation(s)
- Amandeep Kaur
- Whistler Center for Carbohydrate ResearchDepartment of Food SciencePurdue University West Lafayette IN 47907 USA
| | - Tingting Chen
- Whistler Center for Carbohydrate ResearchDepartment of Food SciencePurdue University West Lafayette IN 47907 USA
| | - Stefan J. Green
- Sequencing CoreUniversity of Illinois at Chicago Chicago IL 60612 USA
| | - Ece Mutlu
- Rush University Medical CenterDivision of Digestive Diseases and Nutrition Chicago IL 60612 USA
| | - Berdine R. Martin
- Department of Nutrition SciencePurdue University West Lafayette IN 47907 USA
| | - Pinthip Rumpagaporn
- Department of Food Science and TechnologyKasetsart University Bangkok 10900 Thailand
| | - John A. Patterson
- Department of Animal SciencePurdue University West Lafayette IN 47907 USA
| | - Ali Keshavarzian
- Rush University Medical CenterDivision of Digestive Diseases and Nutrition Chicago IL 60612 USA
| | - Bruce R. Hamaker
- Whistler Center for Carbohydrate ResearchDepartment of Food SciencePurdue University West Lafayette IN 47907 USA
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Kakouros N, Gluckman TJ, Conte JV, Kickler TS, Laws K, Barton BA, Rade JJ. Differential Impact of Serial Measurement of Nonplatelet Thromboxane Generation on Long-Term Outcome After Cardiac Surgery. J Am Heart Assoc 2017; 6:JAHA.117.007486. [PMID: 29097390 PMCID: PMC5721801 DOI: 10.1161/jaha.117.007486] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Systemic thromboxane generation, not suppressible by standard aspirin therapy and likely arising from nonplatelet sources, increases the risk of atherothrombosis and death in patients with cardiovascular disease. In the RIGOR (Reduction in Graft Occlusion Rates) study, greater nonplatelet thromboxane generation occurred early compared with late after coronary artery bypass graft surgery, although only the latter correlated with graft failure. We hypothesize that a similar differential association exists between nonplatelet thromboxane generation and long-term clinical outcome. METHODS AND RESULTS Five-year outcome data were analyzed for 290 RIGOR subjects taking aspirin with suppressed platelet thromboxane generation. Multivariable modeling was performed to define the relative predictive value of the urine thromboxane metabolite, 11-dehydrothromboxane B2 (11-dhTXB2), measured 3 days versus 6 months after surgery on the composite end point of death, myocardial infarction, revascularization or stroke, and death alone. 11-dhTXB2 measured 3 days after surgery did not independently predict outcome, whereas 11-dhTXB2 >450 pg/mg creatinine measured 6 months after surgery predicted the composite end point (adjusted hazard ratio, 1.79; P=0.02) and death (adjusted hazard ratio, 2.90; P=0.01) at 5 years compared with lower values. Additional modeling revealed 11-dhTXB2 measured early after surgery associated with several markers of inflammation, in contrast to 11-dhTXB2 measured 6 months later, which highly associated with oxidative stress. CONCLUSIONS Long-term nonplatelet thromboxane generation after coronary artery bypass graft surgery is a novel risk factor for 5-year adverse outcome, including death. In contrast, nonplatelet thromboxane generation in the early postoperative period appears to be driven predominantly by inflammation and did not independently predict long-term clinical outcome.
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Affiliation(s)
| | | | | | | | | | - Bruce A Barton
- University of Massachusetts Medical School, Worcester, MA
| | - Jeffrey J Rade
- University of Massachusetts Medical School, Worcester, MA .,Johns Hopkins School of Medicine, Baltimore, MD
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Kovarik JJ, Kernbauer E, Hölzl MA, Hofer J, Gualdoni GA, Schmetterer KG, Miftari F, Sobanov Y, Meshcheryakova A, Mechtcheriakova D, Witzeneder N, Greiner G, Ohradanova-Repic A, Waidhofer-Söllner P, Säemann MD, Decker T, Zlabinger GJ. Fasting metabolism modulates the interleukin-12/interleukin-10 cytokine axis. PLoS One 2017; 12:e0180900. [PMID: 28742108 PMCID: PMC5524343 DOI: 10.1371/journal.pone.0180900] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2017] [Accepted: 06/22/2017] [Indexed: 12/22/2022] Open
Abstract
A crucial role of cell metabolism in immune cell differentiation and function has been recently established. Growing evidence indicates that metabolic processes impact both, innate and adaptive immunity. Since a down-stream integrator of metabolic alterations, mammalian target of rapamycin (mTOR), is responsible for controlling the balance between pro-inflammatory interleukin (IL)-12 and anti-inflammatory IL-10, we investigated the effect of upstream interference using metabolic modulators on the production of pro- and anti-inflammatory cytokines. Cytokine release and protein expression in human and murine myeloid cells was assessed after toll-like receptor (TLR)-activation and glucose-deprivation or co-treatment with 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) activators. Additionally, the impact of metabolic interference was analysed in an in-vivo mouse model. Glucose-deprivation by 2-deoxy-D-glucose (2-DG) increased the production of IL-12p40 and IL-23p19 in monocytes, but dose-dependently inhibited the release of anti-inflammatory IL-10. Similar effects have been observed using pharmacological AMPK activation. Consistently, an inhibition of the tuberous sclerosis complex-mTOR pathway was observed. In line with our in vitro observations, glycolysis inhibition with 2-DG showed significantly reduced bacterial burden in a Th2-prone Listeria monocytogenes mouse infection model. In conclusion, we showed that fasting metabolism modulates the IL-12/IL-10 cytokine balance, establishing novel targets for metabolism-based immune-modulation.
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Affiliation(s)
- Johannes J. Kovarik
- Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
- Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University Vienna, Vienna, Austria
| | - Elisabeth Kernbauer
- Max F. Perutz Laboratories, Department of Microbiology and Immunobiology, University of Vienna, Vienna, Austria
| | - Markus A. Hölzl
- Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Johannes Hofer
- Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
- Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University Vienna, Vienna, Austria
| | - Guido A. Gualdoni
- Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Klaus G. Schmetterer
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Fitore Miftari
- Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Yury Sobanov
- Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Anastasia Meshcheryakova
- Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Diana Mechtcheriakova
- Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Nadine Witzeneder
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Georg Greiner
- Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Anna Ohradanova-Repic
- Institute of Hygiene and Applied Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Petra Waidhofer-Söllner
- Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
| | - Marcus D. Säemann
- Department of Internal Medicine III, Clinical Division of Nephrology and Dialysis, Medical University Vienna, Vienna, Austria
| | - Thomas Decker
- Max F. Perutz Laboratories, Department of Microbiology and Immunobiology, University of Vienna, Vienna, Austria
| | - Gerhard J. Zlabinger
- Institute of Immunology, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
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Lachmandas E, van den Heuvel CNAM, Damen MSMA, Cleophas MCP, Netea MG, van Crevel R. Diabetes Mellitus and Increased Tuberculosis Susceptibility: The Role of Short-Chain Fatty Acids. J Diabetes Res 2016; 2016:6014631. [PMID: 27057552 PMCID: PMC4709651 DOI: 10.1155/2016/6014631] [Citation(s) in RCA: 73] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2015] [Accepted: 10/18/2015] [Indexed: 02/07/2023] Open
Abstract
Type 2 diabetes mellitus confers a threefold increased risk for tuberculosis, but the underlying immunological mechanisms are still largely unknown. Possible mediators of this increased susceptibility are short-chain fatty acids, levels of which have been shown to be altered in individuals with diabetes. We examined the influence of physiological concentrations of butyrate on cytokine responses to Mycobacterium tuberculosis (Mtb) in human peripheral blood mononuclear cells (PBMCs). Butyrate decreased Mtb-induced proinflammatory cytokine responses, while it increased production of IL-10. This anti-inflammatory effect was independent of butyrate's well-characterised inhibition of HDAC activity and was not accompanied by changes in Toll-like receptor signalling pathways, the eicosanoid pathway, or cellular metabolism. In contrast blocking IL-10 activity reversed the effects of butyrate on Mtb-induced inflammation. Alteration of the gut microbiota, thereby increasing butyrate concentrations, can reduce insulin resistance and obesity, but further studies are needed to determine how this affects susceptibility to tuberculosis.
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Affiliation(s)
- Ekta Lachmandas
- Department of Internal Medicine and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Internal Postal Code 463, P.O. Box 9101, 6500 HB Nijmegen, Netherlands
- *Ekta Lachmandas:
| | - Corina N. A. M. van den Heuvel
- Department of Internal Medicine and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Internal Postal Code 463, P.O. Box 9101, 6500 HB Nijmegen, Netherlands
| | - Michelle S. M. A. Damen
- Department of Internal Medicine and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Internal Postal Code 463, P.O. Box 9101, 6500 HB Nijmegen, Netherlands
| | - Maartje C. P. Cleophas
- Department of Internal Medicine and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Internal Postal Code 463, P.O. Box 9101, 6500 HB Nijmegen, Netherlands
| | - Mihai G. Netea
- Department of Internal Medicine and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Internal Postal Code 463, P.O. Box 9101, 6500 HB Nijmegen, Netherlands
| | - Reinout van Crevel
- Department of Internal Medicine and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Internal Postal Code 463, P.O. Box 9101, 6500 HB Nijmegen, Netherlands
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Wang FY, Liu JM, Luo HH, Liu AH, Jiang Y. Potential protective effects of Clostridium butyricum on experimental gastric ulcers in mice. World J Gastroenterol 2015; 21:8340-8351. [PMID: 26217085 PMCID: PMC4507103 DOI: 10.3748/wjg.v21.i27.8340] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2015] [Accepted: 05/07/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effects of Clostridium butyricum (C. butyricum) on experimental gastric ulcers (GUs) induced by alcohol, restraint cold stress, or pyloric ligation in mice, respectively.
METHODS: One hundred and twenty mice were randomly allocated into three types of gastric ulcer models (n = 40 each), induced by alcohol, restraint cold stress, or pyloric ligation. In each GU model, 40 mice were allocated into four groups (n = 10 each): the sham control group; model group (GU induction without pretreatment); C. butyricum group (GU induction with C. butyricum pretreatment); and Omeprazole group (GU induction with Omeprazole pretreatment). The effects of C. butyricum were evaluated by examining the histological changes in the gastric mucosal erosion area, the activities of superoxide dismutase (SOD) and catalase (CAT), the level of malondialdehyde (MDA), and the contents of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, leukotriene B4 (LTB4) and 6-keto-PGF-1α (degradation product of PGI2) in the gastric tissue.
RESULTS: Our data showed that C. butyricum significantly reduced the gastric mucosal injury area and ameliorated the pathological conditions of the gastric mucosa. C. butyricum not only minimized the decreases in activity of SOD and CAT, but also reduced the level of MDA in all three GU models used in this study. The accumulation of IL1-β, TNF-α and LBT4 decreased, while 6-keto-PGF-1α increased with pretreatment by C. butyricum in all three GU models.
CONCLUSION: Our data demonstrated the protective effects of pretreatment with C. butyricum on anti-oxidation and anti-inflammation in different types of GU models in mice. Further studies are needed to explore its potential clinical benefits.
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Iraporda C, Errea A, Romanin DE, Cayet D, Pereyra E, Pignataro O, Sirard JC, Garrote GL, Abraham AG, Rumbo M. Lactate and short chain fatty acids produced by microbial fermentation downregulate proinflammatory responses in intestinal epithelial cells and myeloid cells. Immunobiology 2015; 220:1161-9. [PMID: 26101138 DOI: 10.1016/j.imbio.2015.06.004] [Citation(s) in RCA: 200] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2015] [Revised: 05/21/2015] [Accepted: 06/01/2015] [Indexed: 01/22/2023]
Abstract
The use of short chain fatty acids to modulate gastrointestinal inflammatory conditions such as ulcerative colitis has produced encouraging results either in animal models or also in clinical trials. Identifying the key cellular and molecular targets of this activity will contribute to establish the appropriate combinations/targeting strategies to maximize the efficacy of anti-inflammatory interventions. In the present work, we evaluated in vitro the interaction of lactate, acetate, propionate and butyrate on cells relevant for innate immune response of the gastrointestinal tract. All molecules tested regulate the production of proinflammatory cytokines by TLR-4 and TLR-5 activated intestinal epithelial cells in a dose response manner. Furthermore SCFAs and lactate modulate cytokine secretion of TLR-activated bone marrow derived macrophages and also TLR-dependent CD40 upregulation in bone marrow derived dendritic in a dose-dependent manner. Butyrate and propionate have been effective at concentrations of 1 to 5mM whereas acetate and lactate produced modulatory effects at concentrations higher than 20-50mM in different assays. Our results indicate that in concentrations similar to found in large bowel lumen, all SCFAs tested and lactate can modulate activity of relevant sentinel cell types activated by TLR signals. Modulatory activity was not inhibited by pertussis toxin treatment indicating that the effects are not related to Gi signaling. The use of these molecules in combined or separately as intervention strategy in conditions where epithelial or myeloid cells are main triggers of the inflammatory situation seems appropriate.
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Affiliation(s)
- Carolina Iraporda
- Centro de Investigación y Desarrollo en Criotecnología de Alimentos (CIDCA, UNLP-CONICET), Calle 47 y 116, (1900) La Plata, Argentina
| | - Agustina Errea
- Instituto de Estudios Inmunológicos y Fisopatológicos (IIFP, UNLP-CONICET), Calle 47 y 115, (1900) La Plata, Argentina
| | - David E Romanin
- Instituto de Estudios Inmunológicos y Fisopatológicos (IIFP, UNLP-CONICET), Calle 47 y 115, (1900) La Plata, Argentina
| | - Delphine Cayet
- Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, F-59000 Lille, France; Institut National de la Santé et de la Recherche Médicale, U1019, F-59000 Lille, France; Centre National de la Recherche Scientifique, UMR 8204, F-59000 Lille, France; Université Lille Nord de France, F-59000 Lille, France
| | - Elba Pereyra
- Instituto de Biología y Medicina Experimental (IBYME, CONICET), Vuelta de Obligado 2490, CABA (1428), Bs. As., Argentina
| | - Omar Pignataro
- Instituto de Biología y Medicina Experimental (IBYME, CONICET), Vuelta de Obligado 2490, CABA (1428), Bs. As., Argentina; Departamento de Química Biológica - Facultad de Ciencias Exactas y Naturales (FCEyN, UBA), Argentina
| | - Jean Claude Sirard
- Institut Pasteur de Lille, Centre d'Infection et d'Immunité de Lille, F-59000 Lille, France; Institut National de la Santé et de la Recherche Médicale, U1019, F-59000 Lille, France; Centre National de la Recherche Scientifique, UMR 8204, F-59000 Lille, France; Université Lille Nord de France, F-59000 Lille, France
| | - Graciela L Garrote
- Centro de Investigación y Desarrollo en Criotecnología de Alimentos (CIDCA, UNLP-CONICET), Calle 47 y 116, (1900) La Plata, Argentina.
| | - Analía G Abraham
- Centro de Investigación y Desarrollo en Criotecnología de Alimentos (CIDCA, UNLP-CONICET), Calle 47 y 116, (1900) La Plata, Argentina; Área Bioquímica y Control de Alimentos, Facultad de Ciencias Exactas, UNLP. Calle 47 y 115, (1900) La Plata, Argentina
| | - Martín Rumbo
- Instituto de Estudios Inmunológicos y Fisopatológicos (IIFP, UNLP-CONICET), Calle 47 y 115, (1900) La Plata, Argentina
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Pain-associated biomarkers in breast cancer. J Med Life 2015; 8:32-6. [PMID: 25914735 PMCID: PMC4397516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2014] [Accepted: 12/02/2014] [Indexed: 11/04/2022] Open
Abstract
Breast cancer represents a major public health problem, being the highest incidence neoplasia in females in Romania. The most important step in the treatment of this neoplasia is the surgical procedure; the biggest problem associated with this form of treatment in these patients is pain-related. Pain is a complex symptom with an impact on quality of life and psychology of cancer patient and can only be monitored verbally and subjectively. Consequently, the purpose of our work is to identify some biochemical parameters involved in the events cascade associated with inflammation and pain in breast cancer female patients, monitored in dynamics of anesthesia and surgical procedure. Measurements of lipid peroxides, ceruloplasmin and immune circulating complexes in mentioned dynamics have been performed. The recorded values are in concordance with the inflammatory processes and pain intensity, thus we can allege that these measurements can complete the pain-associated clinical picture in female breast cancer patients.
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