Influence of age, hexobarbital, and aniline on NADPH/NADH dependent hydrogen peroxide production in rat hepatic microsomes.
Hepatic microsomal H2O2 production (oxidase function of microsomal cytochrome P-450) is strongly dependent on NADPH or NADH concentration. NADH increases H2O2 production after the addition of a supraoptimal concentration of NADPH to the incubation mixture in all age groups. Maximum activities are found in 60-day-old male Wistar rats. Hexobarbital increased in a dose dependent manner both NADPH, NADH, and NADPH/NADH dependent H2O2 production. Aniline had no effect or slightly decreased H2O2 production. Hexobarbital enhanced NADPH/NADH dependent H2O2 production in all age groups (5-240 days of age) to the same degree. Hence it is concluded that H2O2 production is due to the decay of the peroxycytochrome P-450 complex after the second reduction step via cytochrome b5 and that in all age groups reducibility of cytochrome P-450, which is enhanced by hexobarbital, is rate limiting. As the age course of H2O2 production is similar to that of ethylmorphine N-demethylation, it is concluded that the phenobarbital-inducible cytochrome P-450 subspecies predominantly catalyse H2O2 production.
Klinger
W
W
Freytag
A
A
Schmitt
W
W
D000375:Aging; D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006591:Hexobarbital / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000814:Aniline Compounds; D009243:NAD; D009249:NADP; D003577:Cytochrome P-450 Enzyme System; D006591:Hexobarbital; D006861:Hydrogen Peroxide; C023650:aniline