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

Research output: Contribution to conferenceAbstractAcademic


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; and the Dutch Ministry
of Economic Affairs.
Original languageEnglish
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


Other56th Annual Meeting of the Society of Toxicology
CountryUnited States

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