Glutamine supplementation attenuates ethanol-induced disruption of apical junctional complexes in colonic epithelium and ameliorates gut barrier dysfunction and fatty liver in mice

• Published in: The Journal of nutritional biochemistry Vol. 27; pp. 16 - 26
• Main Authors: Chaudhry, Kamaljit K., Shukla, Pradeep K., Mir, Hina, Manda, Bhargavi, Gangwar, Ruchika, Yadav, Nikki, McMullen, Megan, Nagy, Laura E., Rao, RadhaKrishna
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2016
• Subjects: Adherens junction; Adherens Junctions - drug effects; Alcohol; Animals; Body Weight - drug effects; Cadherin; Claudin; Colon - drug effects; Colon - physiopathology; Ethanol - toxicity; Fatty Liver - physiopathology; Female; Glutamine - administration & dosage; Intestinal Mucosa - drug effects; Intestinal Mucosa - physiopathology; Mice; Mice, Inbred C57BL; Occludin; Oxidative stress; Tight junction; EF; Oxidative stress; EGF; GN; HRP; Gln; ALT; Alcohol; GS; Cadherin; ECL; Adherens junction; Occludin; FITC; ZO-1; PMSF; PF; Claudin; ALD; Tight junction; ERK; GF
• ISSN: 0955-2863; 1873-4847
• DOI: 10.1016/j.jnutbio.2015.08.012

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.