title: Binge ethanol exposure increases liver injury in obese rats.
abstract: OBJECTIVE
  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.
authors.affiliation: 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.
authors.forename: Michal
authors.initials: M
authors.lastname: Carmiel-Haggai
authors.forename: Arthur I
authors.initials: AI
authors.lastname: Cederbaum
authors.forename: Natalia
authors.initials: N
authors.lastname: Nieto
mesh_terms: D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D017209:Apoptosis; D001835:Body Weight; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis; D000431:Ethanol / Q000633:toxicity*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005978:Glutathione / Q000032:analysis; D007473:Ion Channels; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D026901:Membrane Transport Proteins / Q000032:analysis; D024101:Mitochondrial Proteins / Q000032:analysis; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D009765:Obesity / Q000378:metabolism*; D009929:Organ Size; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051381:Rats; D011924:Rats, Zucker; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000071246:Uncoupling Protein 2
chemical_list: D005230:Fatty Acids, Nonesterified; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; C002744:3-nitrotyrosine; D000431:Ethanol; D014443:Tyrosine; D000255:Adenosine Triphosphate; D019392:Cytochrome P-450 CYP2E1; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D005978:Glutathione