Glutamine supplementation attenuates ethanol-induced disruption of apical junctional complexes in colonic epithelium and ameliorates gut barrier dysfunction and fatty liver in mice |
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| Affiliation: | 1. Department of Physiology, University of Tennessee Health Science Center, Memphis, TN;2. Cleveland Clinic Foundation, Cleveland, OH;1. Department of Ecosystem and Public Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, T2N 4Z6, Canada;2. Department of Oncology, Lady Davis Institute for Medical Research, McGill University, Montréal, H3T 1E2, Canada;3. Experimental Medicine, Lady Davis Institute for Medical Research, McGill University, Montréal, H3T 1E2, Canada;4. Department of Medicine, Lady Davis Institute for Medical Research, McGill University, Montréal, H3T 1E2, Canada;1. Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune College of Medicine, Jilin University, Changchun, China;2. College of Biological Sciences, Henan University, Kaifeng, China;3. Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, United States;4. Department of Medical Oncology, Guangzhou First People''s Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China;5. Department of Urology, The First Hospital of Jilin University, Changchun, China;6. Department of Neurosurgery, UT MD Anderson Cancer Center, Houston, TX 77030, United States |
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| Abstract: | Previous in vitro studies showed that glutamine (Gln) prevents acetaldehyde-induced disruption of tight junctions and adherens junctions in Caco-2 cell monolayers and human colonic mucosa. In the present study, we evaluated the effect of Gln supplementation on ethanol-induced gut barrier dysfunction and liver injury in mice in vivo. Ethanol feeding caused a significant increase in inulin permeability in distal colon. Elevated permeability was associated with a redistribution of tight junction and adherens junction proteins and depletion of detergent-insoluble fractions of these proteins, suggesting that ethanol disrupts apical junctional complexes in colonic epithelium and increases paracellular permeability. Ethanol-induced increase in colonic mucosal permeability and disruption of junctional complexes were most severe in mice fed Gln-free diet. Gln supplementation attenuated ethanol-induced mucosal permeability and disruption of tight junctions and adherens junctions in a dose-dependent manner, indicating the potential role of Gln in nutritional intervention to alcoholic tissue injury. Gln supplementation dose-dependently elevated reduced-protein thiols in colon without affecting the level of oxidized-protein thiols. Ethanol feeding depleted reduced protein thiols and elevated oxidized protein thiols. Ethanol-induced protein thiol oxidation was most severe in mice fed with Gln-free diet and absent in mice fed with Gln-supplemented diet, suggesting that antioxidant effect is one of the likely mechanisms involved in Gln-mediated amelioration of ethanol-induced gut barrier dysfunction. Ethanol feeding elevated plasma transaminase and liver triglyceride, which was accompanied by histopathologic lesions in the liver; ethanol-induced liver damage was attenuated by Gln supplementation. These results indicate that Gln supplementation ameliorates alcohol-induced gut and liver injury. |
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