Okadaic acid influences xenobiotic metabolism in HepaRG cells

Authors

  • Leonie T. D. Wuerger German Federal Institute for Risk Assessment, Department of Food Safety, Max-Dohrn-Str. 8-10, 10589 Berlin, Germany https://orcid.org/0000-0002-2441-7252
  • Helen S. Hammer SIGNATOPE GmbH, Markwiesenstraße 55, 72770 Reutlingen, Germany https://orcid.org/0000-0001-8187-0240
  • Ute Hofmann Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Auerbachstr. 112, 70376 Stuttgart, and University of Tübingen, 72074 Tübingen, Germany https://orcid.org/0000-0003-0823-9027
  • Felicia Kudiabor German Federal Institute for Risk Assessment, Department of Food Safety, Max-Dohrn-Str. 8-10, 10589 Berlin, Germany https://orcid.org/0000-0003-2411-753X
  • Holger Sieg German Federal Institute for Risk Assessment, Department of Food Safety, Max-Dohrn-Str. 8-10, 10589 Berlin, Germany, E-mail: holger.sieg@bfr.bund.de https://orcid.org/0000-0002-0593-0173
  • Albert Braeuning German Federal Institute for Risk Assessment, Department of Food Safety, Max-Dohrn-Str. 8-10, 10589 Berlin, Germany https://orcid.org/0000-0003-3810-027X

DOI:

https://doi.org/10.17179/excli2022-5033

Keywords:

okadaic acid, HepaRG cells, CYP enzymes

Abstract

Okadaic acid (OA) is an algae-produced lipophilic marine biotoxin that accumulates in the fatty tissue of filter-feeding shellfish. Ingestion of contaminated shellfish leads to the diarrheic shellfish poisoning syndrome. Furthermore, several other effects of OA like genotoxicity, liver toxicity and tumor-promoting properties have been observed, probably linked to the phosphatase-inhibiting properties of the toxin. It has been shown that at high doses OA can disrupt the physical barrier of the intestinal epithelium. As the intestine and the liver do not only constitute a physical, but also a metabolic barrier against xenobiotic exposure, we here investigated the impact of OA on the expression of cytochrome P450 (CYP) enzymes and transporter proteins in human HepaRG cells liver cells in vitro at non-cytotoxic concentrations. The interplay of OA with known CYP inducers was also studied. Data show that the expression of various xenobiotic-metabolizing CYPs was downregulated after exposure to OA. Moreover, OA was able to counteract the activation of CYPs by their inducers. A number of transporters were also mainly downregulated. Overall, we demonstrate that OA has a significant effect on xenobiotic metabolism barrier in liver cells, highlighting the possibility for interactions of OA exposure with the metabolism of drugs and xenobiotics.

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Published

2022-08-01

How to Cite

Wuerger, L. T. D., Hammer, H. S., Hofmann, U., Kudiabor, F., Sieg, H., & Braeuning, A. (2022). Okadaic acid influences xenobiotic metabolism in HepaRG cells. EXCLI Journal, 21, 1053–1065. https://doi.org/10.17179/excli2022-5033

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