title: Inhibition of drug-metabolizing enzyme activity in human hepatic cytochrome P450s by bisphenol A.
abstract: Effect of bisphenol A on drug-metabolizing enzyme activities by human hepatic cytochrome P450s (CYP) was investigated. We measured aminopyrine N-demethylation by eleven kinds of cDNA-expressed CYPs. CYP2C19 and CYP2B6 catalyzed most efficiently the aminopyrine N-demethylation, followed by CYP2C8 and CYP2D6. Bisphenol A (1 mM) most efficiently inhibited aminopyrine N-demethylation by CYP2C8 and CYP2C19 by 82% and 85%, respectively, whereas inhibition of the activities by CYP 2B6 and 2D6 was less than 40%. Bisphenol A exhibited a noncompetitive-type inhibition of aminopyrine N-demethylase activity by CYP2C8 with Ki value of 97 microM. Additionally, we investigated the inhibitory effect of bisphenol A on CYP2C19-mediated S-mephenytoin 4-hydroxylation. Bisphenol A exhibited a mixed-type inhibition with Ki value of 113 microM. These results suggest that bisphenol A inhibits human hepatic CYP activities, especially CYP2C8 and CYP2C19.
authors.affiliation: Division of Natural Science, Osaka Kyoiku University, Kashiwara, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Niwa
authors.forename: M
authors.initials: M
authors.lastname: Tsutsui
authors.forename: K
authors.initials: K
authors.lastname: Kishimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Yabusaki
authors.forename: F
authors.initials: F
authors.lastname: Ishibashi
authors.forename: M
authors.initials: M
authors.lastname: Katagiri
mesh_terms: D001559:Benzhydryl Compounds; D001711:Biotransformation; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D008862:Microsomes, Liver / Q000201:enzymology*; D010636:Phenols / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D010636:Phenols; D011994:Recombinant Proteins; C006780:bisphenol A; D000098826:Bisphenol A Compounds