Effects of pharmaceuticals on the expression of genes involved in detoxification in a carp primary hepatocyte model

Environmental Science & Technology
Jenna CorcoranCharles R Tyler

Abstract

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 (Cyprinus carpio) primary hepatocytes to the human PXR agonist rifampicin (RIF) on expression of target genes involved in phase I (cyp2k, cyp3a) and phase II (gstα, gstπ) drug metabolism and drug transporters mdr1 and mrp2. RIF induced expression of all target genes measured and the PXR antagonist ketoconazole (KET) inhibited responses of cyp2k and cyp3a. 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 ser...Continue Reading

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Citations

Feb 14, 2014·Biomarkers in Medicine·Albert P Li
Jun 10, 2015·The Science of the Total Environment·Jiannan DingJianchao Liu
Dec 3, 2014·Environmental Research·Sergio Jarque, Benjamin Piña
Aug 19, 2014·The Science of the Total Environment·Christoph SteinbachHana Kocour Kroupova
Aug 5, 2016·Environmental Science and Pollution Research International·A González-MiraA Torreblanca
Jan 27, 2015·Journal of Laboratory Automation·Salman R KhetaniBrenton R Ware
Jul 7, 2017·Journal of Toxicology and Environmental Health. Part a·V CunhaM Ferreira
Dec 5, 2014·Environmental Science and Pollution Research International·N CreusotS Aït-Aïssa
Jul 1, 2017·Analytical and Bioanalytical Chemistry·Jaume AceñaDamià Barceló
Jan 27, 2021·Environmental Pollution·Klaudia ŚwiackaKatarzyna Smolarz

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