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HERO ID
2825953
Reference Type
Journal Article
Title
Regulation of hepatic drug transporter activity and expression by organochlorine pesticides
Author(s)
Bucher, S; Le Vee, M; Jouan, E; Fardel, O
Year
2014
Is Peer Reviewed?
No
Journal
Journal of Biochemical and Molecular Toxicology
ISSN:
1095-6670
EISSN:
1099-0461
Volume
28
Issue
3
Page Numbers
119-128
Language
English
PMID
24464585
DOI
10.1002/jbt.21543
Web of Science Id
WOS:000332141000003
Abstract
Organochlorine (OC) pesticides constitute a major class of persistent and toxic organic pollutants, known to modulate drug-detoxifying enzymes. In the present study, OCs were demonstrated to also alter the activity and expression of human hepatic drug transporters. Activity of the sinusoidal influx transporter OCT1 (organic cation transporter 1) was thus inhibited by endosulfan, chlordane, heptachlor, lindane, and dieldrine, but not by dichlorodiphenyltrichloroethane isomers, whereas those of the canalicular efflux pumps MRP2 (multidrug resistance-associated protein 2) and BCRP (breast cancer resistance protein) were blocked by endosulfan, chlordane, heptachlor, and chlordecone; this latter OC additionally inhibited the multidrug resistance gene 1 (MDR1)/P-glycoprotein (P-gp) activity. OCs, except endosulfan, were next found to induce MDR1/P-gp and MRP2 mRNA expressions in hepatoma HepaRG cells; some of them also upregulated BCRP. By contrast, expression of sinusoidal transporters was not impaired (organic anion-transporting polypeptide (OATP) 1B1 and OATP2B1) or was downregulated (sodium taurocholate co-transporting polypeptide (NTCP) and OCT1). Such regulations of drug transporter activity and expression, depending on the respective nature of OCs and transporters, may contribute to the toxicity of OC pesticides.
Keywords
Organochlorines; Pesticides; Drug Transporter; Liver; Influx; Efflux; Regulation
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