Abstract:
:The purpose of the present study was to assess do selected pesticides as well as their binary combinations act as inhibitors of P-glycoprotein (P-gp) activity of NIH 3T3 mouse fibroblasts stably transfected with human MDR1 gene (NIH 3T3/MDR1). As a result of P-gp inhibition, the increase of intracellular accumulation of a model P-gp substrate fluorescent calcein acetoxymethyl ester was measured. Pesticide and verapamil individual dose-response data were scaled and expressed as percent of maximum effect. Results showed that out of 14 pure pesticides tested, endosulfan, phosalone and propiconazole were nearly as potent as model inhibitor verapamil (EC(50)=1.5μM), while diazinon showed a lower potency of inhibiting P-gp transport activity (EC(50)=58.4μM). Concentrations of pesticides that produced the same inhibiting effect (isoboles) were combined binary. Results calculated using the isobole method revealed that diazinon caused synergistic effect in inhibiting P-gp transport activity in all combinations.
journal_name
Environ Toxicol Pharmacoljournal_title
Environmental toxicology and pharmacologyauthors
Pivčević B,Zaja Rdoi
10.1016/j.etap.2006.04.002subject
Has Abstractpub_date
2006-11-01 00:00:00pages
268-76issue
3eissn
1382-6689issn
1872-7077pii
S1382-6689(06)00060-3journal_volume
22pub_type
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