Influence of bile acids on the cytotoxicity of chemicals in cultivated human hepatocytes

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dc.authorid0000-0001-9511-2010en_US
dc.contributor.authorBrecklinghaus, Tim
dc.contributor.authorAlbrecht, Wiebke
dc.contributor.authorKappenberg, Franziska
dc.contributor.authorDuda, Julia
dc.contributor.authorZhang, Mian
dc.contributor.authorGardner, Iain
dc.contributor.authorTurgunbayer, Özlem Demirci
dc.date.accessioned2023-04-25T12:59:29Z
dc.date.available2023-04-25T12:59:29Z
dc.date.issued2022en_US
dc.departmentDicle Üniversitesi, Fen Fakültesi, Biyoloji Bölümüen_US
dc.description.abstractBile acids (BA) are known to influence the susceptibility of hepatocytes to chemicals. We investigated the cytotoxicity of 18 compounds with known hepatotoxicity status and pharmacokinetics in cultivated primary human hepatocytes with and without the addition of a BA mix to the cell culture medium. This BA mix consisted of physiological ratios of the most abundant human BA at a cholestatic sum concentration of 0.5 mM, which corresponds to 50% of the EC10 (cytotoxicity) of the mix. The BA mix decreased the EC10 of 7 compounds by a factor greater than 1.5, but also increased the EC10 of 5 compounds. The compounds with increased susceptibility include the known hepatotoxicants and BSEP/MRP2 inhibitors rifampicin, ketoconazole, atorvastatin, and cyclosporin A. However, the cytotoxicity of some non-hepatotoxic compounds was also enhanced, among them glucose, which is not known to be an inhibitor of canalicular bile acid export. A recently established technique to quantify how well hepatotoxic and non-hepatotoxic compounds are separated by an in vitro test indicated that the addition of the BA mix did not improve separation. In conclusion, the addition of BA to cultivated hepatocytes leads to a complex situation with increased and decreased susceptibilities depending on the specific compound.en_US
dc.description.sponsorshipGerman Research Foundation (DFG)-RTG 2624 German Research Foundation (DFG)-427806116 Federal Ministry of Education & Research (BMBF)-031L0119en_US
dc.identifier.citationBrecklinghaus, T., Albrecht, W., Kappenberg, F., Duda, J., Zhang, M.A., Gardner, I. ve diğerleri. (2022). Influence of bile acids on the cytotoxicity of chemicals in cultivated human hepatocytes. Toxicology in Vitro, 81, 105344.en_US
dc.identifier.doi10.1016/j.tiv.2022.105344
dc.identifier.endpage9en_US
dc.identifier.issn0887-2333
dc.identifier.issn1879-3177
dc.identifier.pmid35263627
dc.identifier.scopus2-s2.0-85127183474
dc.identifier.scopusqualityQ2
dc.identifier.startpage1en_US
dc.identifier.urihttps://www.sciencedirect.com/science/article/pii/S0887233322000418?via%3Dihub
dc.identifier.urihttps://hdl.handle.net/11468/11744
dc.identifier.volume101en_US
dc.identifier.wosWOS:000795483700006
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorTurgunbayer, Özlem Demirci
dc.language.isoenen_US
dc.publisherPergamon-Elsevier Science LTDen_US
dc.relation.ec681002
dc.relation.ispartofToxicology in Vitro
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.relation.tubitak2219-TUBITAK International Post Doctoral Research Fellowship Program
dc.rightsinfo:eu-repo/semantics/embargoedAccessen_US
dc.subjectDILIen_US
dc.subjectGlycochenodeoxycolic acid (GCDCA)en_US
dc.subjectChenodeoxycholic acid (CDCA)en_US
dc.subjectGlycodeoxycholic acid (GDCA)en_US
dc.subjectDeoxycholic acid (DCA)en_US
dc.subjectGlycocholic acid (GCA)en_US
dc.titleInfluence of bile acids on the cytotoxicity of chemicals in cultivated human hepatocytesen_US
dc.titleInfluence of bile acids on the cytotoxicity of chemicals in cultivated human hepatocytes
dc.typeArticleen_US

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