Effects of dihydrosafrole on cytochromes P-450 and drug oxidation in hepatic microsomes from control and induced rats.
Changes in cytochromes P-450, aminopyrine N-demethylase (APDM), aromatic hydrocarbon (benzo[a]pyrene) hydroxylase (AHH), and type III spectral complex formation were measured in hepatic microsomes of control, phenobarbital (PB)-, and beta-naphthoflavone (beta NF)-induced rats after a single dose of dihydrosafrole (4-n-propyl-1,2-methylenedioxybenzene, DHS). Time profiles of changes in these microsomal parameters were complex and showed that APDM activities and cytochrome P-450 levels decreased immediately after treatment and were associated with concurrent increases in the intensity of the type III methylenedioxyphenyl (MDP) metabolite/cytochrome P-450 spectral complex. In noninduced rats, both APDM activity and cytochrome P-450 levels returned to control levels between 12 and 24 hr after treatment with DHS and subsequently increased above control levels. In PB- and beta NF-induced animals, the inhibitory phases were more prolonged and activity never returned to levels higher than the corresponding controls. AHH activity was increased substantially (two- to three-fold) in all cases after DHS administration. Although displacement of the MDP metabolite/cytochrome P-450 complex with 2-methylbenzimidazole generally led to a marked restoration of cytochrome P-450 levels and partially reversed the inhibition of APDM, it had little or no effect on AHH activities.
D000633:Aminopyrine N-Demethylase / Q000032:analysis; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000032:analysis; D001571:Benzoflavones / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis*; D004149:Dioxoles / Q000633:toxicity*; D004790:Enzyme Induction; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D010084:Oxidation-Reduction; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012451:Safrole / Q000031:analogs & derivatives / Q000633:toxicity*; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D004149:Dioxoles; D004364:Pharmaceutical Preparations; C035396:dihydrosafrole; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D000633:Aminopyrine N-Demethylase; D012451:Safrole; D010634:Phenobarbital