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P‐gp efflux pump inhibition potential of common environmental contaminants determined in vitro
Author(s) -
Georgantzopoulou Anastasia,
Skoczyńska Ewa,
Van den Berg Johannes H.J.,
Brand Walter,
Legay Sylvain,
Klein Sebastian G.,
Rietjens Ivonne M.C.M.,
Murk Albertinka J.
Publication year - 2014
Publication title -
environmental toxicology and chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.1
H-Index - 171
eISSN - 1552-8618
pISSN - 0730-7268
DOI - 10.1002/etc.2493
Subject(s) - efflux , calcein , chemistry , p glycoprotein , atp binding cassette transporter , xenobiotic , multidrug resistance associated protein 2 , biochemistry , transporter , in vitro , lysis , toxicity , environmental chemistry , pharmacology , multiple drug resistance , biology , enzyme , membrane , antibiotics , organic chemistry , gene
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. Environ Toxicol Chem 2014;33:804–813. © 2013 SETAC