Compartmentation and Redox State of Thiols and Proteins During Acute Ethanol Intoxication in Rats

Ethanol is known to affect the cellular content of glutathione and to enhance the lipid peroxidation of biological membranes. However, little is known on intracellular thiol distribution during alcohol intoxication. We report the effect of acute alcohol intoxication on the intracellular compartmentation of free and protein sulfhydryls and the protein redox status in the rat. Oral administration of 25% ethanol (4g/kg) significantly decreased the hepatic concentration of glutathione in cytosol, mitochondria and nuclei. Also, significant changes in the content of sulfhydryl proteins and glutathione bound to proteins were noticed in liver mitochondria, while an enhanced rate of carbonyl protein formation was observed in all the subcellular fractions. The inhibition of acetaldehyde metabolism, but not that of ethanol, exaggerated the observed alterations; in particular, thiols and proteins resulted both oxidatively damaged to a higher extent especially in the mitochondrial compartment. These data indicate that acute ethanol administration differently impairs the redox status of thiols and proteins in the subcellular fractions of rat liver; these alterations seem to depend on acetaldehyde rather than ethanol itself and may be included among the mechanisms underlying alcoholic liver injury.