Effect of phenobarbital and beta-naphthoflavone on oxidative metabolism of N,N-dimethyl-4-aminoazobenzene by regenerating rat-liver microsomes and its response to sulphydryl compounds.
The metabolism of the hepatocarcinogen, N,N-dimethyl-4-aminoazobenzene (DAB) is catalysed by selective forms of cytochrome P-450. DAB metabolism has been studied using microsomes from regenerating rat liver prepared 1, 2, 3, 7 and 10 d after partial hepatectomy. Greatly decreased N-demethylation of DAB was seen during liver regeneration, while virtually no effect on ring-hydroxylation was observed. Glutathione stimulated N-demethylation and ring-hydroxylation of DAB, while metabolism of the corresponding secondary amine N-methyl-4-aminoazobenzene (MAB) was not affected. During regeneration, response to the thiol was depressed in the early stages but later returned to normal. beta-Naphthoflavone (BNF) specifically induced N-demethylation of DAB. Induced activity was not depressed during liver regeneration. Phenobarbital (PB) induced total metabolism, which was depressed during regeneration. This indicates greater stability of BNF-induced cytochrome P-450 compared to control and PB-induced cytochrome P-450. The results indicate that during liver regeneration the metabolism of DAB associated with activation (N-demethylation) is depressed, whereas that associated with detoxication (ring-hydroxylation) is only slightly affected. This confirms the involvement of different forms of cytochrome P-450 in DAB metabolism.
D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D006498:Hepatectomy; D007700:Kinetics; D008115:Liver Regeneration; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D019324:beta-Naphthoflavone; D010128:p-Aminoazobenzene / Q000378:metabolism; D004124:p-Dimethylaminoazobenzene / Q000378:metabolism*
D001571:Benzoflavones; D005419:Flavonoids; D013438:Sulfhydryl Compounds; D010128:p-Aminoazobenzene; D019324:beta-Naphthoflavone; D004124:p-Dimethylaminoazobenzene; D010634:Phenobarbital