Effect of Hydroxyl Radical Scavengers on Microsomal Oxidation of Alcohols and on Associated Microsomal Reactions

The possibility that oxidation of alcohols by liver microsomes represents a system potentially dependent upon the interaction of the alcohols with hydroxyl radicals was evaluated. Mannitol, benzoate, and dimethyl sulfoxide, three compounds that react rapidly with hydroxyl radicals, inhibited microsomal oxidation of ethanol. Whereas only slight inhibition was observed in the absence of a catalase inhibitor, azide, all three scavengers strikingly decreased microsomal oxidation of ethanol in the presence of azide. The inhibition was competitive with respect to ethanol. These agents had no effect on xanthine oxidase-mediated (H2C>2-mediated) oxidation of ethanol, nor did they inhibit microsomal electron transport (NADH- or NADPH-cytochrome c reduction, NADH- or NADPH-dependent oxygen uptake) or the metabolism of aminopyrine or aniline. The oxidation of 1-butanol, which is not an effective substrate for the peroxidatic activity of catalase, was inhibited by dimethyl sulfoxide even in the absence of azide. Whereas microsomal oxidation of ethanol was inhibited 15-25% by azide, butanol oxidation was doubled in the presence of azide. The addition of H202 in the presence of azide resulted in a stimulation of microsomal oxidation of ethanol and butanol in short term experiments. These results are consistent with a mechanism of microsomal oxidation of alcohols which involves the interaction of the alcohols with hydroxyl radicals that are generated from the microsomal electron transfer pathway. Differences in the metabolism of ethanol and 1-butanol may reflect the fact that, whereas ethanol can be oxidized by both a catalase-dependent pathway and a hydroxyl radical pathway, butanol is oxidized only by the latter.