Michal Carmiel-Haggai1, Arthur I Cederbaum, Natalia Nieto. 1. Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, and Division of Livers Diseases, Mount Sinai Medical Center, New York, New York 10029, USA.
Abstract
BACKGROUND & AIMS: The objective of this study was to address the hepatic effects of acute alcohol consumption in obesity by simulating an alcohol binge in genetically obese fa/fa rats compared with lean Fa/? rats. METHODS: Ethanol 4 g/kg or saline was administered by gavage every 12 hours for 3 days. RESULTS: Plasma alcohol levels were similar in both groups. Binge ethanol exposure caused liver injury in obese fa/fa but not in lean Fa/? rats, as assessed by alanine aminotransferase and H&E staining. Obesity impaired the antioxidant defense because basal levels of glutathione, glutamate cysteine ligase modulatory subunit, catalase, glutathione reductase, and superoxide dismutase were lower in fa/fa compared with Fa/? rats; the ethanol binge further decreased these antioxidants in fa/fa rats and also decreased glutathione peroxidase activity. Nonesterified fatty acids and lipid peroxidation were increased after ethanol treatment in fa/fa rats. Cytochrome P450 2E1 was down-regulated in fa/fa compared with Fa/? rats; however, the ethanol binge increased cytochrome P450 2E1 in both genotypes. Adenosine triphosphate decreased and uncoupling protein 2 increased in fa/fa rats treated with ethanol. 3-Nitrotyrosine protein adducts were detected only in fa/fa rats treated with ethanol, and this was accompanied by an induction of inducible nitric oxide synthase. Ethanol binge increased caspase-3 and caspase-8 activity, the expression of Fas ligand, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling in fa/fa rats. CONCLUSIONS: These data indicate that binge drinking increases apoptosis and liver injury in obese rats more than in lean controls and suggest that the injury may involve oxidative and nitrosative damage.
BACKGROUND & AIMS: The objective of this study was to address the hepatic effects of acute alcohol consumption in obesity by simulating an alcohol binge in genetically obese fa/fa rats compared with lean Fa/? rats. METHODS:Ethanol 4 g/kg or saline was administered by gavage every 12 hours for 3 days. RESULTS: Plasma alcohol levels were similar in both groups. Binge ethanol exposure caused liver injury in obese fa/fa but not in lean Fa/? rats, as assessed by alanine aminotransferase and H&E staining. Obesity impaired the antioxidant defense because basal levels of glutathione, glutamate cysteine ligase modulatory subunit, catalase, glutathione reductase, and superoxide dismutase were lower in fa/fa compared with Fa/? rats; the ethanol binge further decreased these antioxidants in fa/fa rats and also decreased glutathione peroxidase activity. Nonesterified fatty acids and lipid peroxidation were increased after ethanol treatment in fa/fa rats. Cytochrome P450 2E1 was down-regulated in fa/fa compared with Fa/? rats; however, the ethanol binge increased cytochrome P450 2E1 in both genotypes. Adenosine triphosphate decreased and uncoupling protein 2 increased in fa/fa rats treated with ethanol. 3-Nitrotyrosine protein adducts were detected only in fa/fa rats treated with ethanol, and this was accompanied by an induction of inducible nitric oxide synthase. Ethanol binge increased caspase-3 and caspase-8 activity, the expression of Fas ligand, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling in fa/fa rats. CONCLUSIONS: These data indicate that binge drinking increases apoptosis and liver injury in obeserats more than in lean controls and suggest that the injury may involve oxidative and nitrosative damage.
Authors: Terrence M Donohue; Natalia A Osna; Casey S Trambly; Nash P Whitaker; Paul G Thomes; Sandra L Todero; John S Davis Journal: Alcohol Clin Exp Res Date: 2011-12-05 Impact factor: 3.455
Authors: Nympha B D'Souza El-Guindy; Elizabeth J Kovacs; Philippe De Witte; Claudia Spies; John M Littleton; Willem J S de Villiers; Amanda J Lott; Timothy P Plackett; Nadine Lanzke; Gary G Meadows Journal: Alcohol Clin Exp Res Date: 2010-06-25 Impact factor: 3.455
Authors: Michael J Duryee; Monte S Willis; Courtney S Schaffert; Roger D Reidelberger; Anand Dusad; Daniel R Anderson; Lynell W Klassen; Geoffrey M Thiele Journal: Am J Physiol Gastrointest Liver Physiol Date: 2013-11-27 Impact factor: 4.052
Authors: Mohamed A Abdelmegeed; Sehwan Jang; Atrayee Banerjee; James P Hardwick; Byoung-Joon Song Journal: Free Radic Biol Med Date: 2013-02-27 Impact factor: 7.376
Authors: Sarah M Denucci; Ming Tong; Lisa Longato; Margot Lawton; Mashiko Setshedi; Rolf I Carlson; Jack R Wands; Suzanne M de la Monte Journal: Gastroenterol Res Pract Date: 2010-08-16 Impact factor: 2.260
Authors: Suzanne M de la Monte; Lisa Longato; Ming Tong; Sarah DeNucci; Jack R Wands Journal: Int J Environ Res Public Health Date: 2009-07-23 Impact factor: 3.390