Cytochrome P450 Oxidase Activity and Its Role in NADPH Dependent Lipid Peroxidation
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A comparison is made between microsomal NADPH-dependent H2O2 production and malondialdehyde (MDA) formation in rat liver microsomes, obtained from phenobarbital pretreated rats. An increase in H2O2 formation was observed during NADPH-dependent disposition (10 min) of 100 microM diazepam (33%) and 2 mM hexobarbital (69%). In contrast orphenadrine (100 microM) and its mono-N-demethylated metabolite tofenacine (100 microM) decreased the H2O2 formation (35% and 55%, respectively). However, all these substrates were found to inhibit NADPH-dependent lipid peroxidation (60 min), estimated by measuring MDA formation, to various extents. These data strongly suggest that the oxidase activity of cytochrome P450 (H2O2 production) is not involved in a rate-limiting step in NADPH-dependent lipid peroxidation.
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