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Okadaic acid influences xenobiotic metabolism in HepaRG cells
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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Leibniz Research Centre for Working Environment and Human Factors
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9489895/ https://www.ncbi.nlm.nih.gov/pubmed/36172076 http://dx.doi.org/10.17179/excli2022-5033 |
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author | Wuerger, Leonie T.D. Hammer, Helen S. Hofmann, Ute Kudiabor, Felicia Sieg, Holger Braeuning, Albert |
author_facet | Wuerger, Leonie T.D. Hammer, Helen S. Hofmann, Ute Kudiabor, Felicia Sieg, Holger Braeuning, Albert |
author_sort | Wuerger, Leonie T.D. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9489895 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Leibniz Research Centre for Working Environment and Human Factors |
record_format | MEDLINE/PubMed |
spelling | pubmed-94898952022-09-27 Okadaic acid influences xenobiotic metabolism in HepaRG cells Wuerger, Leonie T.D. Hammer, Helen S. Hofmann, Ute Kudiabor, Felicia Sieg, Holger Braeuning, Albert EXCLI J Original Article 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. Leibniz Research Centre for Working Environment and Human Factors 2022-08-01 /pmc/articles/PMC9489895/ /pubmed/36172076 http://dx.doi.org/10.17179/excli2022-5033 Text en Copyright © 2022 Wuerger et al. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ) You are free to copy, distribute and transmit the work, provided the original author and source are credited. |
spellingShingle | Original Article Wuerger, Leonie T.D. Hammer, Helen S. Hofmann, Ute Kudiabor, Felicia Sieg, Holger Braeuning, Albert Okadaic acid influences xenobiotic metabolism in HepaRG cells |
title | Okadaic acid influences xenobiotic metabolism in HepaRG cells |
title_full | Okadaic acid influences xenobiotic metabolism in HepaRG cells |
title_fullStr | Okadaic acid influences xenobiotic metabolism in HepaRG cells |
title_full_unstemmed | Okadaic acid influences xenobiotic metabolism in HepaRG cells |
title_short | Okadaic acid influences xenobiotic metabolism in HepaRG cells |
title_sort | okadaic acid influences xenobiotic metabolism in heparg cells |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9489895/ https://www.ncbi.nlm.nih.gov/pubmed/36172076 http://dx.doi.org/10.17179/excli2022-5033 |
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