Pesticides and their binary combinations as P-glycoprotein inhibitors in NIH 3T3/MDR1 cells.

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.

authors

Pivčević B,Zaja R

doi

10.1016/j.etap.2006.04.002

subject

Has Abstract

pub_date

2006-11-01 00:00:00

pages

268-76

issue

3

eissn

1382-6689

issn

1872-7077

pii

S1382-6689(06)00060-3

journal_volume

22

pub_type

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