John Wiley & Sons, Ltd.

P‐gp efflux pump inhibition potential of common environmental contaminants determined in vitro

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Across different species, cellular efflux pumps such as P‐glycoprotein (P‐gp, MDR1) serve as a first line of defence by transporting toxic xenobiotics out of the cell. This mechanism is also active in aquatic organisms such as mussels, fish and their larvae. Modulation of this resistance mechanism by chemical agents occurring in the environment could result in either higher or lower internal concentrations of toxic and/ or endogenous compounds in cells. The aim of the present study was to explore and quantify the inhibition of the P‐gp efflux pumps by several ubiquitous aquatic contaminants. The calcein‐AM assay commonly used in pharmacological research was established with P‐gp over‐expressing Madin‐Darby Canine Kidney cells (MDCKII‐MDR1) in a 96‐well plate, avoiding extra washing, centrifugation and lysis steps. This calcein‐AM based P‐gp cellular efflux pump inhibition assay, here further abbreviated as CEPIA, was used to study the inhibition by commonly occurring environmental contaminants. Among others, the compounds pentachlorophenol, perfluorooctanesulfonate and perfluorooctanoate strongly inhibited the P‐gp mediated efflux of calcein‐AM while the chloninated alkanes did not seem to interact with the transporter. The fact that common pollutants can be potent modulators of the efflux transporters is a motive to further study whether this increases the toxicity of other contaminants present in the same matrices. Environ Toxicol Chem © 2013 SETAC

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