LIPID-PEROXIDATION IN RATS CHRONICALLY FED ETHANOL

Chronic alcohol consumption induces cytochrome P450IIE1, enabling habi tual abusers to consume far greater quantities of alcohol than normal subjects. This pathway of metabolism leads to the production of free r adical species, which cause tissue damage through peroxidation of cell membranes. Groups of Wistar rats of equal male: female ratio (n=24) w ere fed alcohol by gavage twice daily to achieve a dosage of 15 g/kg b ody weight. Mean peak blood alcohol concentrations of 186 mg% were pro duced in males and 156 mg% in females. The animals were allowed free a ccess to standard laboratory chow and water. Control animals were pair -fed to the alcoholic group and fed isocaloric glucose by gavage. Grou ps of animals were killed between 9 and 11 am on consecutive mornings, after nocturnal feeding, since it has previously been shown that fast ing rapidly depletes hepatic glutathione concentrations. Hepatic gluta thione was measured by a spectrophotometric enzymatic recycling proced ure. As a marker of lipid peroxidation hepatic malonaldehyde (MDA) was measured by high performance Liquid chromatography. Hepatic MDA was i ncreased in the alcoholic group (p<0.001), as was total hepatic glutat hione (p<0.0001). Masma concentrations of alpha-tocopherol were increa sed in the alcoholic group, but ascorbic acid and superoxide dismutase values were nor affected. No sex differences were detected. The incre ased MDA production in the alcohol group is strong evidence that lipid peroxidation is a mechanism of alcoholic tissue damage. The rise in h epatic glutathione may be an adaptive response to free radical product ion that protects the rat against tissue damage.