Integrated non-targeted metabolomics and lipidomics reveal mechanisms of fluorotelomer sulfonates-induced toxicity in human hepatocytes

文献类型： 外文期刊

第一作者： Zheng, Yuanyuan

作者： Zheng, Yuanyuan;Gao, Yafei;Chen, Hao;Sun, Hongwen;Zhao, Hongzhi;Zheng, Yuanyuan;Pan, Yuanjiang;Wang, Lu;Wu, Jianing;Xiang, Li

作者机构：

关键词： Fluorotelomer sulfonates; Environmental pollutants; Metabolomics; Lipidomics; Biotransformation

期刊名称：ENVIRONMENT INTERNATIONAL （ 影响因子：9.7； 五年影响因子：11.6 ）

ISSN： 0160-4120

年卷期： 2024 年 193 卷

页码：

收录情况： SCI

摘要： Fluorotelomer sulfonates (FTSs) are widely used as novel substitutes for perfluorooctane sulfonate, inevitably leading to FTSs accumulation in various environmental media and subsequent exposure to humans. This accumulation eventually poses environmental hazards and health risks. However, their toxicity mechanisms remain unclear. Herein, the mechanisms of two FTSs (6:2 and 8:2 FTS) induced toxicity in human hepatocellular carcinoma cells were investigated via non-targeted metabolomics and lipidomics based on liquid chromatography-high resolution mass spectrometry. Our results revealed that amino acid, purine, acylcarnitine and lipid levels were significantly perturbed by 6:2 and 8:2 FTS exposure. The effects of 8:2 FTS exposure were largely characterized by up-regulation of pyruvate metabolism pathway and down-regulation of purine metabolism pathway, whereas the opposite trends were induced by 6:2 FTS exposure. The opposite trends were confirmed by the mRNA expression levels of four key genes (glyoxalase 1, adenylosuccinate lyase, inosine monophosphate dehydrogenase 1 (IMPDH1) and IMPDH2) determined by real-time PCR. Common lipid perturbations included significantly increased ceramide/sphingomyelin ratios, and obvious accumulation of hexosylceramides and lysoglycerophospholipids. 6:2 FTS exposure induced sharp accumulation of glycerides, including monoglycerides, diglycerides and triglycerides. 8:2 FTS exposure induced decreased levels of acylcarnitines and fatty acids. Both of 6:2 and 8:2 FTS exposure induced increased levels of intracellular reactive oxygen species, an imbalance in energy metabolism homeostasis, and mitochondrial dysfunction. The results of integrated omics analysis are expected to serve as valuable information for the health risk assessment of 6:2 FTS and 8:2 FTS.

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