title: 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 (K(i)(app) = 848.3 microM) and carbamazepine (K(i)(app) = 1023.1 microM), 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.
authors.affiliation: Département des sciences biologiques, Université du Québec à Montréal, Montréal, Quebec, Canada.
authors.forename: M-A
authors.initials: MA
authors.lastname: Verner
authors.forename: T
authors.initials: T
authors.lastname: Magher
authors.forename: S
authors.initials: S
authors.lastname: Haddad
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000378:metabolism; D000818:Animals; D000890:Anti-Infective Agents / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism; D001559:Benzhydryl Compounds; D002220:Carbamazepine / Q000378:metabolism; D002478:Cells, Cultured; D004347:Drug Interactions; D052244:Endocrine Disruptors / Q000378:metabolism*; D020719:Glucuronides / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism*; D008658:Inactivation, Metabolic; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009288:Naproxen / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010636:Phenols / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020156:Salicylic Acid / Q000378:metabolism; D000098826:Bisphenol A Compounds
chemical_list: D018712:Analgesics, Non-Narcotic; D000890:Anti-Infective Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001559:Benzhydryl Compounds; D002220:Carbamazepine; D052244:Endocrine Disruptors; D020719:Glucuronides; D009288:Naproxen; D004364:Pharmaceutical Preparations; D010636:Phenols; D020156:Salicylic Acid; C025256:nonylphenol; C006780:bisphenol A; D000098826:Bisphenol A Compounds