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

Abstract

1. 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.

2. This study aimed to identify and characterize the potential metabolic interactions between 14 drugs and these two endocrine disruptors.

3. 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 (K_iapp = 848.3 μM) and carbamazepine (K_iapp = 1023.1 μM), 2) no inhibition by salicylic acid suggesting another mechanism of inhibition.

4. 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.

Keywords::

• Bisphenol A
• p-nonylphenol
• drugs
• interactions
• hepatocytes
• microsomes
• metabolism
• rat

Acknowledgements

Declaration of interest

This study was supported by a Discovery Grant from the National Sciences and Engineering Research Council of Canada (NSERC). Sami Haddad was recipient of a research scholarship junior 1 from the Fonds de Recherche en Santé du Québec (FRSQ). Analytical instruments used in this study were funded by Canadian Funds for Innovation (CFI).