Biochemical markers of predisposition to ethanolinduced liver damage

Abstract

A new approach to identification of the factors, responsible for predisposition to ethanol-induced liver damage, was developed. It is based on the examination of the liver in the same animals both before (biochemistry) and after (histology, blood markers of liver damage) chronic alcohol administration and comparison the biochemical and histological sets of data, using the methods of multiple stepwise regression, correlation, canonical analyses and ANOVA. The experiments were carried out in 118 male Wistar rats (250-300 g). In 94 animals the central and left lateral hepatic lobes (~65-70% of the liver weight) were removed under anaesthesia with a ligation of the lobar bases. Two months later, after liver recovery (confirmed by biochemistry and histology), they were administered ethanol (30% water solution, 5 g/kg, intragastrically, once a day, for 57 days). Control animals after the same hepatectomy operation received the same volumes of water instead of ethanol. It was found that animals with initially higher activity of alcohol dehydrogenase and lipid peroxidation system and lower contents of reduced glutathione, retinols and cytochrome b5, lower activity of UDP-glucuronyl-, glutathione-S-transferases and rate of NADH oxidation in the liver had higher ethanol-induces liver damage indicated by histology and increased alanine and aspartate aminotransferase activities in blood. Those rats were also more sensitive to the hypnotic effect of ethanol. The proposed animal model and approach can be used in the finding of other biomarkers of the sensitivity to the hepatotoxic effect of ethanol (predisposition to the alcohol-induced liver damage) as well as biomarkers of the sensitivity to other hepatotoxins.