Cytochrome P450 oxidase activity and its role in NADPH dependent lipid peroxidation.
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.
D000818:Animals; D007700:Kinetics; D008054:Lipid Peroxides / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D009249:NADP / Q000378:metabolism*; D009251:NADPH-Ferrihemoprotein Reductase; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D008054:Lipid Peroxides; D008315:Malondialdehyde; D009249:NADP; D010088:Oxidoreductases; D009251:NADPH-Ferrihemoprotein Reductase; D010634:Phenobarbital