Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 430329
Title Inhibition of cellular efflux pumps involved in multi xenobiotic resistance (MXR) in echinoid larvae as a possible mode of action for increased ecotoxicological risk of mixtures
Author(s) Drs Anselmo, H.M.R.; Berg, J.H.J. van den; Rietjens, I.; Murk, A.J.
Source Ecotoxicology 21 (2012)8. - ISSN 0963-9292 - p. 2276 - 2287.
DOI https://doi.org/10.1007/s10646-012-0984-2
Department(s) Sub-department of Toxicology
WIMEK
Publication type Refereed Article in a scientific journal
Publication year 2012
Keyword(s) multixenobiotic defense-mechanism - mussel mytilus-galloprovincialis - urchin psammechinus-miliaris - p-glycoprotein - aquatic organisms - pluronic p85 - drug efflux - marine mussel - bivalve gills - in-vitro
Abstract In marine organisms the multi xenobiotic resistance (MXR) mechanism via e.g. P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) is an important first line of defense against contaminants by pumping contaminants out of the cells. If compounds would impair the MXR mechanism, this could result in increased intracellular levels of other compounds, thereby potentiating their toxicity. A calcein-AM based larval cellular efflux pump inhibition assay (CEPIA) was developed for echinoid (Psammechinus miliaris) larvae and applied for several contaminants. The larval CEPIA revealed that triclosan (TCS) and the nanoparticles P-85® (P-85) were 124 and 155× more potent inhibitors (IC50 0.5 ± 0.05 and 0.4 ± 0.1 µM, respectively) of efflux pumps than the model inhibitor Verapamil (VER). PFOS (heptadecafluorooctane sulfonic acid) and pentachlorophenol also were more potent than VER, 24 and 5×, respectively. Bisphenol A and o,p'-dichlorodiphenyltrichloroethane (o,p'-DDT) inhibited efflux pumps with a potency 3× greater than VER. In a 48 h early life stage bioassay with P. miliaris, exposure to a non-lethal concentration of the inhibitors TCS, VER, the model MRP inhibitor MK-571, the nanoparticles P-85 and the model P-gp inhibitor PSC-833, increased the toxicity of the toxic model substrate for efflux pumps vinblastine by a factor of 2, 4, 4, 8 and 16, respectively. Our findings show that several contaminants accumulating in the marine environment inhibit cellular efflux pumps, which could potentiate toxic effects of efflux pumps substrates
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