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Ochratoxin A secretion by ATP-dependent membrane transporters in Caco-2 cells

  • Toxicokinetics and Metabolism
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Abstract

The ATP-dependent membrane transporters, P-gp, MRP2 and BCRP, localized in the luminal membranes of the intestines, liver and kidney, counteract absorption and increase excretion of xenobiotics and drugs. Previously, it has been suggested that the mycotoxin ochratoxin A (OTA) is a substrate for ATP-dependent transporters, and hence the absorption and secretion of OTA in the Caco-2 cell model was investigated. To this end, Caco-2 cells were cultured as confluent monolayers in bicameral inserts and the transepithelial transport of the mycotoxin was assessed. Caco-2 cells secreted OTA to the luminal side in a concentration-dependent manner. This secretory permeability was higher than the absorptive permeability, while the absorptive permeability remained constant for all OTA concentrations tested. The secretion decreased and absorption increased in the presence of the MRP-inhibitor MK571, the P-gp and BCRP inhibitor GF120918, and the BCRP-inhibitor Ko143, suggesting that the secretion of OTA is mediated by MRP2 and BCRP. Cyclosporine A also decreased the secretory permeability, but did not affect absorptive permeability, while PSC833 did neither change absorption nor secretion of OTA. Hence it can be suggested that OTA is a substrate for MRP2 as well as BCRP. These findings are of interest in evaluating mycotoxin absorption after oral ingestion, tissue distribution and particularly excretion pathways, including renal, biliary and mammary gland excretion.

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Acknowledgements

Authors greatly appreciate the gift of Prof. Dr. G.J. Koomen and the Van ‘t Hoff Institute for Molecular Sciences, Universiteit van Amsterdam, providing us with Ko 143 for the inhibition studies. Moreover, we thank the Bi-national Graduate School “Molecular Mechanisms in Food Toxicology” (University of Düsseldorf) and particularly Prof. G. Degen (Institut für Arbeitsphysiologie an der Universität Dortmund) for their kind support of Y. Lektarau.

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  1. Department of Veterinary Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 16, 3584 CM, Utrecht, The Netherlands

    Jan Schrickx & J. Fink-Gremmels

  2. Institute of Occupational Physiology, The University of Dortmund, Ardeystrasse 67, 44139, Dortmund, Germany

    Yuri Lektarau

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  1. Jan Schrickx
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  2. Yuri Lektarau
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Correspondence to Jan Schrickx.

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Schrickx, J., Lektarau, Y. & Fink-Gremmels, J. Ochratoxin A secretion by ATP-dependent membrane transporters in Caco-2 cells. Arch Toxicol 80, 243–249 (2006). https://doi.org/10.1007/s00204-005-0041-5

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