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