Integration of proteomics and network toxicology reveals the mechanism of mercury chloride induced hepatotoxicity, in mice and HepG2 cells.
Xin CaoKanmin MaoYanan ZhangMiao YangHongjuan LiuXinzheng WangLiping HaoPublished in: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (2023)
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.
Keyphrases
- drug induced
- epidermal growth factor receptor
- fatty acid
- diabetic rats
- oxidative stress
- high glucose
- mass spectrometry
- heavy metals
- small cell lung cancer
- tyrosine kinase
- public health
- signaling pathway
- risk assessment
- transcription factor
- machine learning
- south africa
- electronic health record
- cell proliferation
- early onset
- type diabetes
- advanced non small cell lung cancer
- high fat diet induced
- label free
- toll like receptor
- social media
- immune response
- induced apoptosis
- fluorescent probe
- human health
- ischemia reperfusion injury
- data analysis
- mental health
- replacement therapy
- diffusion weighted imaging