Cuykx Matthias, Beirnaert Charlie, Rodrigues Robim Marcelino, Laukens Kris, Vanhaecke Tamara, Covaci Adrian
Toxicological Centre, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
Research Group In Vitro Toxicology and Dermato-Cosmetology (IVTD), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Jette, Belgium.
Metabolites. 2019 Nov 4;9(11):265. doi: 10.3390/metabo9110265.
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 ( = 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.
代谢物代表了细胞组织最下游的信息。因此，代谢组学实验对于揭示毒理学作用模式中涉及的内源性途径极具价值。然而，每一种外部刺激都会引起细胞稳态的改变，从而掩盖所涉及的内源性途径，使结果的解释产生偏差。在此，我们报告糖精钠的情况，它被认为无肝毒性，因此可作为一种参考化合物，用于检测与肝毒性无关的代谢变化。将HepaRG细胞暴露于高水平的糖精钠（>10 mM）会导致细胞死亡，这可能是由于渗透压升高所致。然而，在每天暴露于5 mM糖精钠72小时后，脂质组中也观察到少量（n = 15）显著改变的代谢物，包括磷脂略有减少和三酰甘油增加。一种无肝毒性的化合物能够影响代谢组，这一观察结果凸显了在通过代谢组学研究毒理学作用模式时正确实验设计和数据解释的重要性。
