ETHANOL-INDUCED CHANGES OF INTRACELLULAR THIOL COMPARTMENTATION AND PROTEIN REDOX STATUS IN THE RAT-LIVER - EFFECT OF TAUROURSODEOXYCHOLATE

Background/Aims: Ethanol impairs cellular antioxidant defense and prot ein 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 intox ication in the liver and the effect of tauroursodeoxycholate pretreatm ent, Methods: The concentrations of total glutathione, glutathione bou nd to proteins, sulfhydryl proteins, carbonyl proteins and malondialde hyde were measured in hepatic cytosol, mitochondria and nuclei after o ral administration of 25% ethanol (4 g/kg) or isocaloric carbohydrate solution to rats. The metabolisms of ethanol and acetaldehyde were inv estigated 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 receive d tauroursodeoxycholate (12 mg/kg p.os) 1 h before ethanol ingestion, Results: Ethanol significantly decreased the glutathione concentration s, Significant increases in glutathione bound to proteins, carbonyl pr otein and malondialdehyde concentrations were also noted, especially a t the mitochondrial level, Enhanced carbonyl protein formation was als o observed (p<0.01), The inhibition of acetaldehyde metabolism, but no t ethanol metabolism, exaggerated the alterations produced by ethanol, Pretreatment with tauroursodeoxycholate significantly reduced lipid a nd protein oxidation, particularly in mitochondria, By contrast, no ch anges were observed in glutathione content and compartmentation,Conclu sions: Ethanol intoxication differentially impairs thiol and protein r edox status in the subcellular fractions of rat liver, These alteratio ns seem dependent on acetaldehyde rather than ethanol, Tauroursodeoxyc holate administration protects proteins and lipids from ethanol-induce d oxidative damage without influencing the glutathione content and com partmentation.