Next Article in Journal
Heat Stress-Induced Metabolic Remodeling in Saccharomyces cerevisiae
Next Article in Special Issue
Glucose-6 Phosphate, A Central Hub for Liver Carbohydrate Metabolism
Previous Article in Journal
Seasonal Variations and Interspecific Differences in Metabolomes of Freshwater Fish Tissues: Quantitative Metabolomic Profiles of Lenses and Gills
Previous Article in Special Issue
A Lipidomic Analysis of Docosahexaenoic Acid (22:6, ω3) Mediated Attenuation of Western Diet Induced Nonalcoholic Steatohepatitis in Male Ldlr -/- Mice
Open AccessArticle

Exposure of HepaRG Cells to Sodium Saccharin Underpins the Importance of Including Non-Hepatotoxic Compounds When Investigating Toxicological Modes of Action Using Metabolomics

1
Toxicological Centre, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium
2
Research Group In Vitro Toxicology and Dermato-Cosmetology (IVTD), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Jette, Belgium
3
Department of Mathematics & Computer Science, University of Antwerp, Middelheimlaan 1, 2020 Antwerp, Belgium
4
Biomedical Informatics Network Antwerpen (Biomina), University of Antwerp, Middelheimlaan 1, 2020 Antwerp, Belgium
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Metabolites 2019, 9(11), 265; https://doi.org/10.3390/metabo9110265
Received: 10 October 2019 / Revised: 30 October 2019 / Accepted: 30 October 2019 / Published: 4 November 2019
(This article belongs to the Special Issue Metabolism and Metabolomics of Liver in Health and Disease)
Metabolites represent the most downstream information of the cellular organisation. Hence, metabolomics experiments are extremely valuable to unravel the endogenous pathways involved in a toxicological mode of action. However, every external stimulus can introduce alterations in the cell homeostasis, thereby obscuring the involved endogenous pathways, biasing the interpretation of the results. Here we report on sodium saccharin, which is considered to be not hepatotoxic and therefore can serve as a reference compound to detect metabolic alterations that are not related to liver toxicity. Exposure of HepaRG cells to high levels of sodium saccharin (>10 mM) induced cell death, probably due to an increase in the osmotic pressure. Yet, a low number (n = 15) of significantly altered metabolites were also observed in the lipidome, including a slight decrease in phospholipids and an increase in triacylglycerols, upon daily exposure to 5 mM sodium saccharin for 72 h. The observation that a non-hepatotoxic compound can affect the metabolome underpins the importance of correct experimental design and data interpretation when investigating toxicological modes of action via metabolomics. View Full-Text
Keywords: in vitro; HepaRG; sodium saccharin; reference toxicants in vitro; HepaRG; sodium saccharin; reference toxicants
Show Figures

Figure 1

MDPI and ACS Style

Cuykx, M.; Beirnaert, C.; Rodrigues, R.M.; Laukens, K.; Vanhaecke, T.; Covaci, A. Exposure of HepaRG Cells to Sodium Saccharin Underpins the Importance of Including Non-Hepatotoxic Compounds When Investigating Toxicological Modes of Action Using Metabolomics. Metabolites 2019, 9, 265.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop