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  3. Transcriptomics integrated with metabolomics unravels the interweaving of inflammatory response and 1-stearoyl-2-arachidonoyl-sn-glycerol metabolic disorder in chronic cadmium exposure-induced hepatotoxicity

Transcriptomics integrated with metabolomics unravels the interweaving of inflammatory response and 1-stearoyl-2-arachidonoyl-sn-glycerol metabolic disorder in chronic cadmium exposure-induced hepatotoxicity

  • Environ Toxicol Pharmacol. 2023 Jun 7;104172. doi: 10.1016/j.etap.2023.104172.
Rongrong Hao 1,  Heng Xiao 2,  Hui Wang 1,  Ping Deng 1,  Yang Yue 1,  Jingdian Li 1,  Yan Luo 1,  Li Tian 1,  Jia Xie 1,  Mengyan Chen 1,  Zhou Zhou 3,  Fengqiong Chen 4,  Huifeng Pi 5,  Zhengping Yu 6
Affiliations

Affiliations

  • 1 Department of Occupational Health (Key Laboratory of Electromagnetic Radiation Protection, Ministry of Education), Third Military Medical University, Chongqing, China.
  • 2 Anorectal Section, Zhuzhou Hospital Affiliated to Xiangya Shool of Medicine, Central South University, Zhuzhou, Hunan, China.
  • 3 Center for Neurointelligence, School of Medicine, Chongqing University, Chongqing, China.
  • 4 Chongqing Center for Disease Control and Prevention, Chongqing, China. Electronic address: [email protected].
  • 5 Department of Occupational Health (Key Laboratory of Electromagnetic Radiation Protection, Ministry of Education), Third Military Medical University, Chongqing, China. Electronic address: [email protected].
  • 6 Department of Occupational Health (Key Laboratory of Electromagnetic Radiation Protection, Ministry of Education), Third Military Medical University, Chongqing, China. Electronic address: [email protected].
PMID: 37295737 DOI: 10.1016/j.etap.2023.104172
Abstract

Chronic Cd exposure induces an inflammatory response that contributes to liver damage. In the present study, C57BL/6J mice (8 weeks) were administered CdCl2 (0.6mg/L) orally for 6 months, and the underlying mechanism of chronic Cd-induced hepatotoxicity was explored through the application of transcriptomics and metabolomics. Chronic Cd exposure induced focal necrosis and inflammatory cell infiltration in the livers of mice. Importantly, hepatic IL-1β, IL-6, IL-9, IL-10, IL-17 and GM-CSF levels were significantly increased following chronic Cd exposure. Ingenuity Pathway Analysis of the transcriptomics profiles combined with RTqPCR was used to identify and optimize a crucial inflammatory response network in chronic Cd hepatotoxicity. Furthermore, an integrative analysis combining inflammatory response genes with differential metabolites revealed that 1-stearoyl-2-arachidonoyl-sn-glycerol and 4-hydroxybutanoic acid lactone levels were significantly correlated with all inflammatory response genes. Overall, our findings in this study help decipher the underlying mechanisms and key molecular events of chronic Cd hepatotoxicity.

Keywords

Cd; hepatotoxicity; inflammation; metabolomics; transcriptomics.

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