title: Glutamine supplementation attenuates ethanol-induced disruption of apical junctional complexes in colonic epithelium and ameliorates gut barrier dysfunction and fatty liver in mice.
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.
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, TN.
authors.forename: Kamaljit K
authors.initials: KK
authors.lastname: Chaudhry
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, TN.
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Shukla
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, TN.
authors.forename: Hina
authors.initials: H
authors.lastname: Mir
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, TN.
authors.forename: Bhargavi
authors.initials: B
authors.lastname: Manda
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, TN.
authors.forename: Ruchika
authors.initials: R
authors.lastname: Gangwar
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, TN.
authors.forename: Nikki
authors.initials: N
authors.lastname: Yadav
authors.affiliation: Cleveland Clinic Foundation, Cleveland, OH.
authors.forename: Megan
authors.initials: M
authors.lastname: McMullen
authors.affiliation: Cleveland Clinic Foundation, Cleveland, OH.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Nagy
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, TN. Electronic address: rrao2@uthsc.edu.
authors.forename: RadhaKrishna
authors.initials: R
authors.lastname: Rao
mesh_terms: D022005:Adherens Junctions / Q000187:drug effects*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003106:Colon / Q000187:drug effects* / Q000503:physiopathology; D000431:Ethanol / Q000633:toxicity*; D005234:Fatty Liver / Q000503:physiopathology*; D005260:Female; D005973:Glutamine / Q000008:administration & dosage*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D005973:Glutamine; D000431:Ethanol
keywords: Adherens junction; Alcohol; Cadherin; Claudin; Occludin; Oxidative stress; Tight junction