Abstract

Genistein is a natural phytoestrogen of the soybean, and bisphenol A (BPA) is a synthetic chemical used in the production of polycarbonate plastics. Both genistein and BPA disrupt the endocrine system in vivo and in vitro. Growing concerns of altered xenobiotic metabolism due to concomitant exposures from soy milk in BPA-laden baby bottles has warranted the investigation of the glucuronidation rate of genistein in the absence and presence (25 μM) of BPA by human liver microsomes (HLM) and rat liver microsomes (RLM). HLM yield V_max values of 0.93 ± 0.10 nmol · min⁻¹ · mg⁻¹ and 0.62 ± 0.05 nmol · min⁻¹ · mg⁻¹ in the absence and presence of BPA, respectively. K_m values for genistein glucuronidation by HLM in the absence and presence of BPA are 15.1 ± 7.9 μM and 21.5 ± 7.7 μM, respectively, resulting in a K_i value of 58.7 μM for BPA. Significantly reduced V_max and unchanged K_m in the presence of BPA in HLM are suggestive of noncompetitive inhibition. In RLM, the presence of BPA resulted in a K_i of 35.7 μM, an insignificant change in V_max (2.91 ± 0.26 nmol · min⁻¹ · mg⁻¹ and 3.05 ± 0.41 nmol · min⁻¹ · mg⁻¹ in the absence and presence of BPA, respectively), and an increase in apparent K_m (49.4 ± 14 μM with no BPA and 84.0 ± 28 μM with BPA), indicative of competitive inhibition. These findings are significant because they suggest that BPA is capable of inhibiting the glucuronidation of genistein in vitro, and that the type of inhibition is different between HLM and RLM.