Inhibition of benzo(a)pyrene monooxygenase by alpha-naphthoflavone may be partially mediated by the metabolite 9-hydroxy-alpha-naphthoflavone.
alpha-Naphthoflavone (ANF) inhibits beta-naphthoflavone-induced rat liver microsomal benzo(a)pyrene metabolism and is transformed by these microsomes into alpha-naphthoflavone metabolites. We determined the inhibitory effect on benzo(a)pyrene (B(a)P) metabolism of several of these metabolites and of 6-methoxy-ANF, using beta-naphthoflavone-induced rat liver microsomes. 9-Hydroxy-ANF was the most active inhibitor (I50 = 1.47 microM) and was metabolized from ANF by these hepatic microsomes in concentrations which are inhibitory. Therefore, 9-hydroxy-ANF a microsomal metabolite of ANF, may play a role in the inhibition of B(a)P oxidation by ANF.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors*; D001571:Benzoflavones / Q000378:metabolism / Q000494:pharmacology*; D001579:Benzopyrene Hydroxylase / Q000037:antagonists & inhibitors*; D001711:Biotransformation; D005419:Flavonoids / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats
D001571:Benzoflavones; D005419:Flavonoids; C011512:alpha-naphthoflavone; C036721:9-hydroxy-alpha-naphthoflavone; D001579:Benzopyrene Hydroxylase; D001189:Aryl Hydrocarbon Hydroxylases