title: Ethanol-induced changes of intracellular thiol compartmentation and protein redox status in the rat liver: effect of tauroursodeoxycholate.
abstract: OBJECTIVE
  Ethanol impairs cellular antioxidant defense and protein metabolism. Hydrophilic bile acids are protective against ethanol-induced cytotoxicity. This study investigated the compartmentation of intracellular thiol and protein redox status after acute ethanol intoxication in the liver and the effect of tauroursodeoxycholate pretreatment.
  
  
  METHODS
  The concentrations of total glutathione, glutathione bound to proteins, sulfhydryl proteins, carbonyl proteins and malondialdehyde were measured in hepatic cytosol, mitochondria and nuclei after oral administration of 25% ethanol (4 g/kg) or isocaloric carbohydrate solution to rats. The metabolisms of ethanol and acetaldehyde were investigated by giving 4-methylpyrazole (1 mmol/kg i.p.) or cyanamide (15 mg/kg i.p.) 1 h prior to ethanol ingestion. One group of rats received tauroursodeoxycholate (12 mg/kg p.os) 1 h before ethanol ingestion.
  
  
  RESULTS
  Ethanol significantly decreased the glutathione concentrations. Significant increases in glutathione bound to proteins, carbonyl protein and malondialdehyde concentrations were also noted, especially at the mitochondrial level. Enhanced carbonyl protein formation was also observed (p < 0.01). The inhibition of acetaldehyde metabolism, but not ethanol metabolism, exaggerated the alterations produced by ethanol. Pretreatment with tauroursodeoxycholate significantly reduced lipid and protein oxidation, particularly in mitochondria. By contrast, no changes were observed in glutathione content and compartmentation.
  
  
  CONCLUSIONS
  Ethanol intoxication differentially impairs thiol and protein redox status in the subcellular fractions of rat liver. These alterations seem dependent on acetaldehyde rather than ethanol. Tauroursodeoxycholate administration protects proteins and lipids from ethanol-induced oxidative damage without influencing the glutathione content and compartmentation.
authors.affiliation: Department of Internal and Occupational Medicine, University of Bari, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Vendemiale
authors.forename: I
authors.initials: I
authors.lastname: Grattagliano
authors.forename: A
authors.initials: A
authors.lastname: Signorile
authors.forename: E
authors.initials: E
authors.lastname: Altomare
mesh_terms: D000079:Acetaldehyde / Q000378:metabolism; D000428:Alcohol Drinking / Q000378:metabolism*; D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D003484:Cyanamide / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000378:metabolism* / Q000494:pharmacology*; D000077604:Fomepizole; D005978:Glutathione / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D011506:Proteins / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology*
chemical_list: D011506:Proteins; D011720:Pyrazoles; D013438:Sulfhydryl Compounds; D000431:Ethanol; D003484:Cyanamide; D008315:Malondialdehyde; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; D000077604:Fomepizole; D005978:Glutathione; D000079:Acetaldehyde