EFFECT OF ETHANOL AND OF ITS INTERACTION WITH ASCORBIC-ACID OR TOCOPHEROL-ACETATE ON P-NITROBENZOIC ACID REDUCTION AND ON LIPID-PEROXIDATION

It is known that ethanol induces oxidative-reductive drug biotransform ations. Of these, reductions have been studied less than oxidations. P -450, particularly after the induction caused by ethanol, functions al so as an oxidase in which free radicals are involved. Hepatotoxicity o f ethanol is most probably caused by these species. We examined the ef fect of ethanol, ethanol and ascorbic acid or ethanol and tocopherol-A c on the reduction of p-nitrobenzoic acid, on hepatic microsomal lipid peroxidation and on liver microsomal P-450. It was found that ethanol increased significantly the nitro-group reduction in vivo and in vitr o, as well as the conjugation of p-aminobenzoic acid. It also caused s ignificant hepatic microsomal lipid peroxidation but no significant in crease of microsomal P-450. Treatment with ethanol and ascorbic acid p roduced no significant alterations of the effects of ethanol alone. Si multaneous treatment with ethanol and tocopherol-Ac caused statistical ly significant increase of the in vitro reduction of p-nitrobenzoic ac id and reversal of the hepatic microsomal lipid peroxidation induced b y ethanol.Our results are discussed on the basis of free radical proce sses which intervene with the function of P-450 after the treatment wi th ethanol.