Prevention of ethanol-induced changes in reactive oxygen parameters by alpha-tocopherol

Rats were given a 200 mg/kg body weight daily dose of alpha-tocopherol by i.p. injection for 15 days. This resulted in elevated levels of glutathione in both liver and brain, and in a reduced hepatic rate of generation of reactive oxygen species. The depression of hepatic and cerebral glutathione levels in ethanol-consuming rats was prevented by simultaneous treatment with alpha-tocopherol. Other putative indices of hepatic pro-oxidant events, namely levels of mixed function oxidase and proteolytic activity, were elevated by alpha-tocopherol both in the presence and absence of ethanol. In addition, levels of enzymes especially susceptible to oxidative degradation, glutamine synthetase and creatine kinase, were depressed in the liver following treatment with ethanol or alpha-tocopherol. Parameters rapidly responsive to oxidative changes revealed the antioxidant property of alpha-tocopherol, while protein-based indices reflecting more extended events suggested a pro-oxidant effect of this vitamin. Results suggest that high levels of alpha-tocopherol can simultaneously lead to a more reduced intracellular environment and yet to localized evidence of enhanced oxidative events.