High concentrations of commonly used drugs can inhibit the in vitro glucuronidation of bisphenol A and nonylphenol in rats

Abstract

4-n-Nonylphenol and bisphenol A are endocrine disrupting chemicals that are mainly detoxified through glucuronidation. A factor that may modulate their glucuronidation rates is co-exposure to pharmaceuticals.This study aimed to identify and characterize the potential metabolic interactions between 14 drugs and these two endocrine disruptors.Nonylphenol and bisphenol A were co-incubated in freshly isolated rat hepatocytes with, drugs at a high concentration. Statistically significant metabolic inhibition of bisphenol A and nonylphenol biotransformation was observed with nine drugs (>50% inhibition by naproxen, salicylic acid, carbamazepine and mefenamic acid). Inhibition assays of UGT activity in rat liver microsomes revealed: 1) competitive inhibition by naproxen (Kiapp = 848.3 μM) and carbamazepine (Kiapp = 1023.1 μM), 2) no inhibition by salicylic acid suggesting another mechanism of inhibition.Detoxification of nonylphenol and bisphenol A was shown to be impaired by excessive concentrations of many drugs and health risk assessment should therefore address this issue.