CAUSE OF DECREASE OF ETHYLMORPHINE N-DEMETHYLASE ACTIVITY BY LIPID PEROXIDATION IN MICROSOMES FROM THE RAT, GUINEA PIG AND RABBIT

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There were marked differences among animal species between NADPH-dependent and ascorbic acid-Fe⁺⁺-dependent lipid peroxidation. In NADPH-dependent lipid peroxidation, this activity occurred to the greatest extent in rats followed by guinea pigs and rabbits and such was much lower in rabbits than in guinea pigs. On the other hand, rabbit microsomes exhibited higher lipid peroxidation activity than guinea pigs in ascorbic acid plus Fe⁺⁺ or Fe⁺⁺-dependent lipid peroxidation although the activity was still lower than in rats. The ascorbic acid plus Fe⁺⁺-stimulated lipid peroxidation produced a decrease in ethylmorphine N-demethylase activity which was closely related to ethylmorphine-enhanced NADPH-cytochrome P-450 reductase activity but was not related to the change of the apparent content of cytochrome P-450 in all animal species. These results indicate that decrease of NADPH-cytochrome P-450 reductase activity induces a decrease in ethylmorphine N-demethylase activity by lipid peroxidation.