engleski

Inhibitory potency of pesticides on multixenobiotic transporter P-glycoprotein in NIH 3T3/MDR1 mouse fibroblasts

Phenomenon of multixenobiotic resistance (MXR) of aquatic organisms is generally associated with the over expression of an ATP transmembrane transporter P-glycoprotein (P-gp). P-gp mediates the efflux of wide variety of xenobiotics from the cell thereby protecting cell from their accumulation and potential toxic effect. Substances that can inhibit MXR by inhibiting activity of its P-gp pump are called MXR-inhibitors, also known as chemosensitizers since they are sensitizing cells by making them more vulnerable to toxic chemicals. The purpose of the present study was to assess ; a) whether 9 structurally diverse pure pesticides and their commercial suspensions have potency to inhibit P-gp, and b) whether 6 pesticides known endocrine disruptors (ED) express P-gp inhibiting property. Experiments were conducted using "P-gp accumulation" assay: NIH 3T3 mouse fibroblasts stabile transfected with MDR1 gene (NIH3T3/MDR1) which codes for P-gp, and a P-gp substrate calcein acetoxymethyl ester (Ca-AM). Based on EC50 pesticides were ranged for their P-pg inhibiting potency starting from highest endosulfan, phosalone, propiconazol, chlorpyriphos, diazinon, while fenoxycarb, dimethoate, malathion and methomyl showed no effect. Higher concentrations of commercial mixtures were needed to elicit the same effect. Among ED pesticides only endosulfan inhibited P-gp pumping activity.

MXR ; pesticides ; endocrine disruptors

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