Role of hydroxyl radicals in microsomal oxidation of alcohols.

A series of hydroxyl radical (.OH) scavenging agents competitively inhibited microsomal oxidation of ethanol and 1-butanol. The inhibition by the scavengers was specific since these agents had no effect on catalase-dependent oxidation of ethanol, microsomal drug metabolism or microsomal electron transfer. Chemical evidence for production of .OH during microsomal electron transfer was provided by the generation of appropriate products from .OH scavenging agents. H2O2 was shown to play a role as a precursor of .OH. Fe-EDTA increased microsomal oxidation of ethanol without affecting drug metabolism. A role for cytochrome P-450 in catalyzing . OH generation remains to be evaluated. These results suggest that the molecular mechanism underlying the oxidation of ethanol by liver microsomes reflects the ability of ethanol to interact with .OH generated from microsomal electron transfer.