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

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

Environment International (Nov 2024)

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

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

Affiliations

Yuanyuan Zheng: MOE Key Laboratory of Pollution Processes and Environmental Criteria, College of Environmental Science and Engineering, Nankai University, Tianjin 300350, China; Department of Chemistry, Zhejiang University, Hangzhou 310058, Zhejiang, China
Lu Wang: Institute of Germplasm Resource and Biotechnology, Tianjin Academy of Agricultural Sciences, Tianjin 300384, China
Jianing Wu: Institute of Germplasm Resource and Biotechnology, Tianjin Academy of Agricultural Sciences, Tianjin 300384, China
Li Xiang: State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China
Yafei Gao: MOE Key Laboratory of Pollution Processes and Environmental Criteria, College of Environmental Science and Engineering, Nankai University, Tianjin 300350, China
Hao Chen: MOE Key Laboratory of Pollution Processes and Environmental Criteria, College of Environmental Science and Engineering, Nankai University, Tianjin 300350, China
Hongwen Sun: MOE Key Laboratory of Pollution Processes and Environmental Criteria, College of Environmental Science and Engineering, Nankai University, Tianjin 300350, China
Yuanjiang Pan: Department of Chemistry, Zhejiang University, Hangzhou 310058, Zhejiang, China; Corresponding authors.
Hongzhi Zhao: MOE Key Laboratory of Pollution Processes and Environmental Criteria, College of Environmental Science and Engineering, Nankai University, Tianjin 300350, China; Corresponding authors.

Journal volume & issue: Vol. 193
p. 109092

Abstract

Read online

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.

Published in Environment International

ISSN: 0160-4120 (Print)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Geography. Anthropology. Recreation: Environmental sciences
Website: https://www.journals.elsevier.com/environment-international

About the journal

Abstract

Keywords