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Integration of proteomics and network toxicology reveals the mechanism of mercury chloride induced hepatotoxicity, in mice and HepG2 cells.

Authors :
Cao, Xin
Mao, Kanmin
Zhang, Yanan
Yang, Miao
Liu, Hongjuan
Wang, Xinzheng
Hao, Liping
Source :
Food & Chemical Toxicology. Jul2023, Vol. 177, pN.PAG-N.PAG. 1p.
Publication Year :
2023

Abstract

Mercury is one heavy metal toxin that could cause severe health impairments. Mercury exposure has become a global environmental issue. Mercury chloride (HgCl 2) is one of mercury's main chemical forms, but it lacks detailed hepatotoxicity data. The present study aimed to investigate the mechanism of hepatotoxicity induced by HgCl 2 through proteomics and network toxicology at the animal and cellular levels. HgCl 2 showed apparent hepatotoxicity after being administrated with C57BL/6 mice (16 mg/kg.bw, oral once a day, 28 days) and HepG2 cells (100 μmol/L, 12 h). Otherwise, oxidative stress, mitochondrial dysfunction and inflammatory infiltration play an important role in HgCl 2 -induced hepatotoxicity. The differentially expressed proteins (DEPs) after HgCl 2 treatment and enriched pathways were obtained through proteomics and network toxicology. Western blot and qRT-PCR results showed acyl-CoA thioesterase 1 (ACOT1), acyl-CoA synthetase short chain family member 3 (ACSS3), epidermal growth factor receptor (EGFR), apolipoprotein B (APOB), signal transducer and activator of transcription 3 (STAT3), alanine--glyoxylate aminotransferase (AGXT), cytochrome P450 3A5 (CYP3A5), CYP2E1 and CYP1A2 may be the major biomarkers for HgCl 2 -induced hepatotoxicity, which involved chemical carcinogenesis, fatty acid metabolism, CYPs-mediated metabolism, GSH metabolism and others. Therefore, this study can provide scientific evidence for the biomarkers and mechanism of HgCl 2 -induced hepatotoxicity. • Oxidative stress, mitochondrial dysfunction and inflammation play an important role in HgCl 2 -induced hepatotoxicity. • Proteomics and network toxicology were combined for studying hepatotoxic mechanism. • ACOT1, ACSS3, EGFR, APOB, STAT3, AGXT, CYP2E1 and 3A5 may be the potential biomarkers for HgCl 2 -induced hepatotoxicity. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
02786915
Volume :
177
Database :
Academic Search Index
Journal :
Food & Chemical Toxicology
Publication Type :
Academic Journal
Accession number :
164259999
Full Text :
https://doi.org/10.1016/j.fct.2023.113820