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1000 Titel
  • More than additive effects on liver triglyceride accumulation by combinations of steatotic and non-steatotic pesticides in HepaRG cells
1000 Autor/in
  1. Lasch, Alexandra |
  2. Marx-Stoelting, Philip |
  3. Braeuning, Albert |
  4. Lichtenstein, Dajana |
1000 Erscheinungsjahr 2021
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-02-11
1000 Erschienen in
1000 Quellenangabe
  • 95(4):1397-1411
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1007/s00204-021-02997-2 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032629/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • The liver is constantly exposed to mixtures of hepatotoxic compounds, such as food contaminants and pesticides. Dose addition is regularly assumed for mixtures in risk assessment, which however might not be sufficiently protective in case of synergistic effects. Especially the prediction of combination effects of substances which do not share a common adverse outcome (AO) might be problematic. In this study, the focus was on the endpoint liver triglyceride accumulation in vitro, an indicator of hepatic fatty acid changes. The hepatotoxic compounds difenoconazole, propiconazole and tebuconazole were chosen which cause hepatic fatty acid changes in vivo, whereas fludioxonil was chosen as a hepatotoxic substance not causing fatty acid changes. Triglyceride accumulation was analyzed for combinations of steatotic and non-steatotic pesticides in human HepaRG hepatocarcinoma cells. Investigations revealed a potentiation of triglyceride accumulation by mixtures of the steatotic compounds with the non-steatotic fludioxonil, as compared to the single compounds. Mathematical modeling of combination effects indicated more than additive effects for the tested combinations if the method by Chou was applied, and a decrease in EC
1000 Sacherschließung
lokal Nuclear receptor activation
lokal Carcinoma, Hepatocellular/metabolism [MeSH]
lokal Liver steatosis
lokal Cell Line, Tumor [MeSH]
lokal Liver/pathology [MeSH]
lokal Adverse outcome pathway
lokal In Vitro Systems
lokal Liver/metabolism [MeSH]
lokal Fatty Acids/metabolism [MeSH]
lokal Liver/drug effects [MeSH]
lokal Pesticides
lokal Liver Neoplasms/metabolism [MeSH]
lokal Models, Theoretical [MeSH]
lokal Dioxolanes/toxicity [MeSH]
lokal Dioxolanes/administration
lokal Pyrroles/administration
lokal Triazoles/toxicity [MeSH]
lokal Pyrroles/toxicity [MeSH]
lokal Humans [MeSH]
lokal Dioxoles/administration
lokal Dioxoles/toxicity [MeSH]
lokal Triglycerides/metabolism [MeSH]
lokal Hep G2 Cells [MeSH]
lokal Fatty Liver/chemically induced [MeSH]
lokal Adverse Outcome Pathways [MeSH]
lokal Triazoles/administration
lokal Pesticides/toxicity [MeSH]
lokal Mixtures
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/uri/TGFzY2gsIEFsZXhhbmRyYQ==|https://frl.publisso.de/adhoc/uri/TWFyeC1TdG9lbHRpbmcsIFBoaWxpcA==|https://orcid.org/0000-0003-3810-027X|https://frl.publisso.de/adhoc/uri/TGljaHRlbnN0ZWluLCBEYWphbmE=
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1000 Erstellt am 2023-05-11T14:32:50.734+0200
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1000 Zuletzt bearbeitet Tue Oct 24 07:58:15 CEST 2023
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