Abstract
The effects of preincubation of microsomes with ascorbate or ferrous ion or NADPH-generating system on activities of drug metabolizing enzymes, content of cytochrome P-450 and the activities of NADPH-linked cytochrome c reductase and neotetrazolium diaphorase were investigated. Demethylase activities of aminopyrine, ethylmorphine and codeine were markedly decreased by the stimulation of microsomal lipid peroxidation whereas hydroxylation of aniline was only slightly reduced. On the other hand, content of cytochrome P-450 and activities of NADPH-cytochrome c reductase and NADPH-neotetrazolium diaphorase were only slightly changed by the stimulation of microsomal lipid peroxidation. Aminopyrine N-demethylation was inhibited by carbon monoxide but lipid peroxidation was increased. Furthermore, synergism of NADPH-dependent drug oxidation by NADH which has been reported by Estabrook, et al. was not observed in lipid peroxidation.
