Interaction of bisphenol A with rat hepatic cytochrome P450 enzymes

Abstract

The effect of bisphenol A (BPA) on the kinetics of cytochrome P450 (P450)-dependent monooxygenases in rat liver microsomes was studied. Testosterone 16β-hydroxylase (TS16BH) and testosterone 2α-hydroxylase (TS2AH) activities were extensively inhibited by BPA at 100 μM (69% and 74%, respectively). The inhibition type was mixed for both P450-dependent monooxyganases. The K i of TS16BH and TS2AH from Lineweaver–Burk plots were 25.9 and 24.9 μM, respectively. The activities of acetanilide 4-hydroxylase (AA4H), 7-ethoxycoumarin O-deethylase (ECOD), bufuralol 1′-hydroxylase (BF1′H), chlorzoxazone 6-hydroxylase (CZ6H) and testosterone 6β-hydroxylase (TS6BH) were also effectively inhibited by BPA at 100 μM (43–52%). The inhibition type of these P450-dependent monooxygenases was mixed or uncompetitive, and the K is (50.5–88.5 μM) were higher than those of TS16BH and TS2AH. By contrast, the values of IC 50 and K i of testosterone 7α-hydroxylase (TS7AH) and lauric acid ω-hydroxylase (LAOH) for BPA were >1000 μM. These results suggest that BPA interacts with rat hepatic CYP1A2, CYP2A2, CYP2B2, CYP2C11, CYP2D1, CYP2E1 and CYP3A2 in vitro.