Effects of Pharmaceuticals on the Expression of Genes Involved in Detoxification in a Carp Primary Hepatocyte Model Jenna Corcoran Anke Lange Matthew J. Winter Charles R. Tyler 10.1021/es3005305.s001 https://acs.figshare.com/articles/journal_contribution/Effects_of_Pharmaceuticals_on_the_Expression_of_Genes_Involved_in_Detoxification_in_a_Carp_Primary_Hepatocyte_Model/2517037 Fish in many surface freshwaters are exposed to a range of pharmaceuticals via wastewater treatment works effluent discharges. In mammals the pregnane X receptor (PXR) plays a key role in the regulation of a suite of genes involved in drug biotransformation, but information on the role of this response pathway in fish is limited. Here we investigated the effects of exposure of carp (<i>Cyprinus carpio</i>) primary hepatocytes to the human PXR agonist rifampicin (RIF) on expression of target genes involved in phase I (<i>cyp2k</i>, <i>cyp3a</i>) and phase II (<i>gstα</i>, <i>gstπ</i>) drug metabolism and drug transporters <i>mdr1</i> and <i>mrp2</i>. RIF induced expression of all target genes measured and the PXR antagonist ketoconazole (KET) inhibited responses of <i>cyp2k</i> and <i>cyp3a</i>. Exposure of the primary carp hepatocytes to the pharmaceuticals ibuprofen (IBU), clotrimazole (CTZ), clofibric acid (CFA) and propranolol (PRP), found responses to IBU and CFA, but not CTZ or PRP. This is in contrast with mammals, where CTZ is a potent PXR-agonist. Collectively our data indicate potential PXR involvement in regulating selected genes involved in drug metabolism in fish, but suggest some divergence in the regulation pathways with those in mammals. The carp primary hepatocyte model serves as a useful system for screening for responses in these target genes involved in drug metabolism. 2012-06-05 00:00:00 cyp 2k cyp 3a cyp 3a Exposure drug metabolism mammal target genes wastewater treatment works effluent discharges drug transporters mdr 1 expression PXR antagonist ketoconazole CTZ pharmaceutical hepatocyte regulation PRP pregnane X receptor KET IBU PXR agonist rifampicin role pathway II phase response gst CFA mrp 2. RIF