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

“Across different species, cellular efflux pumps such as P-glycoprotein (P-gp; also termed multidrug resistance protein 1
[MDR1]) serve as a first line of defense 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 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-acetoxymethyl ester
(calcein-AM) assay commonly used in pharmacological research was established with P-gp–overexpressing 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 (CEPIA) was used to study the inhibition by commonly occurring environmental contaminants. Among
others, the compounds pentachlorophenol, perfluorooctane sulfonate, 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.”
© 2013 SETAC
(Citaat: Georgabtzopoulou, A., Skoczynska, E. et al. – P-gp efflux pump inhibition potential of common environmental contaminants determined in vitro – Environmental Toxicology and Chemistry 33(2014)4, p.804-813)