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GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Oats Supplementation Prevents Alcohol-Induced Gut Leakiness in Rats by Preventing Alcohol-Induced Oxidative Tissue Damage

Division of Digestive Disease and Nutrition, Departments of Internal Medicine (Y.T., C.B.F., A.B., J.Z.F., A.K.), Pharmacology (A.B., A.K.), Molecular Biophysics and Physiology (A.B., A.K.), and Biochemistry (C.B.F.), Rush University, Chicago, Illinois

We reported previously that oats supplementation prevents gut leakiness and alcoholic steatohepatitis (ASH) in our rat model of alcoholic liver disease. Because oxidative stress is implicated in the pathogenesis of both alcohol-induced gut leakiness and ASH, and because oats have antioxidant properties, we tested the hypothesis that oats protect by preventing alcohol-induced oxidative damage to the intestine. Male Sprague-Dawley rats were gavaged for 12 weeks with alcohol (starting dose of 1 g/kg increasing to 6 g/kg/day over the first 2 weeks) or dextrose, with or without oats supplementation (10 g/kg/day). Oxidative stress and injury were assessed by measuring colonic mucosal inducible nitric-oxide synthase (iNOS) (by immunohistochemistry), nitric oxide (colorimetric assay), and protein carbonylation and nitrotyrosination (immunoblotting). Colonic barrier integrity was determined by assessing the integrity of the actin cytoskeleton (immunohistochemistry) and the integrity of tight junctions (electron microscopy). Oats supplementation prevented alcohol-induced up-regulation of iNOS, nitric oxide overproduction in the colonic mucosa, and increases in protein carbonyl and nitrotyrosine levels. This protection was associated with prevention of ethanol (EtOH)-induced disorganization of the actin cytoskeleton and disruption of tight junctions. We conclude that oats supplementation attenuates EtOH-induced disruption of intestinal barrier integrity, at least in part, by inhibiting EtOH-induced increases in oxidative stress and oxidative tissue damage. This inhibition prevents alcohol-induced disruption of the cytoskeleton and tight junctions. This study suggests that oats may be a useful therapeutic agent—a nutraceutical—for the prevention of alcohol-induced oxidative stress and organ dysfunction.

Address correspondence to: Dr. Ali Keshavarzian, Rush University Medical Center, 1725 W. Harrison, Suite 206, Chicago, IL 60612. E-mail: ali_keshavarzian{at}rush.edu