Dose-Dependent Increase of Triglyceride Levels in Human HepaRG Liver Cells Exposed to the Fungicide Cyproconazole

A.A.C.M. Peijnenburg, Deborah Rijkers, G.M. Stoopen

    Research output: Contribution to conferenceAbstract

    Abstract

    Cyproconazole is a triazole antifungal which has been associated with
    the development of hepatic steatosis, also referred to as fatty liver
    disease, in rodents. An Adverse Outcome Pathway (AOP) for steatosis has
    recently been proposed and one important Key Event (KE) in this AOP
    concerns the accumulation of triglycerides. The present work is part of
    a larger effort that aims to explore the usefulness of the human liver cell
    line HepaRG as an in vitro system to address various KEs in the steatosis
    AOP and to test foodborne chemicals and chemical mixtures for steatogenic
    properties. In this study, HepaRG cells were exposed for 24 and
    72 hours to increasing, non-cytotoxic, concentrations of cyproconazole.
    Upon exposure, cells were lysed by sonication and extracted with a
    mixture of iso-octane and ethylacetate (75:25) to specifically extract
    triglycerides. For further analysis of the fatty acid composition of the
    triglycerides, extracts were treated with sodium methoxide and BF3 to
    generate fatty acid methyl esters (FAMEs). Triglycerides and FAMEs were
    analysed using Gas Chromatography with Flame Ionization Detection
    (GC-FID). The results indicated that cyproconazole treatment of HepaRG
    cells results in a dose-dependent accumulation of triglycerides. The
    effect was strongest after 72 hours of exposure. Accumulation was most
    pronounced for C50, C52, and C54 triglycerides containing mainly C16
    and C18 fatty acids. This outcome underlines the value of the HepaRG
    cell line as a model system for studying toxicant-induced liver steatosis.
    Acknowledgement: This work has been funded by the EU project EuroMix
    (Grant Agreement 633172; www.euromixproject.eu) and the Dutch Ministry
    of Economic Affairs.
    Original languageEnglish
    Pages361-361
    Publication statusPublished - 16 Mar 2017
    Event56th Annual Meeting of the Society of Toxicology: Continuing Education Courses and Scientific Sessions - Baltimore, United States
    Duration: 12 Mar 201716 Mar 2017

    Other

    Other56th Annual Meeting of the Society of Toxicology
    Country/TerritoryUnited States
    CityBaltimore
    Period12/03/1716/03/17

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