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Integration of metabolomics and proteomics reveals the underlying hepatotoxic mechanism of perfluorooctane sulfonate (PFOS) and 6:2 chlorinated polyfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA) in primary human hepatocytes

Authors :
Chuanhai Li
Lidan Jiang
Yuan Qi
Donghui Zhang
Xinya Liu
Wenchao Han
Wanli Ma
Lin Xu
Yuan Jin
Jiao Luo
Kunming Zhao
Dianke Yu
Source :
Ecotoxicology and Environmental Safety, Vol 249, Iss , Pp 114361- (2023)
Publication Year :
2023
Publisher :
Elsevier, 2023.

Abstract

Perfluorooctane sulfonate (PFOS) and its alternative 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) are ubiquitous in various environmental and human samples. They have been reported to have hepatotoxicity effects, but the potential mechanisms remain unclear. Herein, we integrated metabolomics and proteomics analysis to investigate the altered profiles in metabolite and protein levels in primary human hepatocytes (PHH) exposed to 6:2 Cl-PFESA and PFOS at human exposure relevant concentrations. Our results showed that 6:2 Cl-PFESA exhibited higher perturbation effects on cell viability, metabolome and proteome than PFOS. Integration of metabolomics and proteomics revealed that the alteration of glycerophospholipid metabolism was the critical pathway of 6:2 Cl-PFESA and PFOS-induced lipid metabolism disorder in primary human hepatocytes. Interestingly, 6:2 Cl-PFESA-induced cellular metabolic process disorder was associated with the cellular membrane-bounded signaling pathway, while PFOS was associated with the intracellular transport process. Moreover, the disruption effects of 6:2 Cl-PFESA were also involved in inositol phosphate metabolism and phosphatidylinositol signaling system. Overall, this study provided comprehensive insights into the hepatic lipid toxicity mechanisms of 6:2 Cl-PFESA and PFOS in human primary hepatocytes.

Details

Language :
English
ISSN :
01476513
Volume :
249
Issue :
114361-
Database :
Directory of Open Access Journals
Journal :
Ecotoxicology and Environmental Safety
Publication Type :
Academic Journal
Accession number :
edsdoj.78adc25c84133aa2d9be820e4a916
Document Type :
article
Full Text :
https://doi.org/10.1016/j.ecoenv.2022.114361