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

Abstract

Chronic Cd exposure induces an inflammatory response that contributes to liver damage. In the present study, C57BL/6 J mice (8 weeks) were administered CdCl2 (0.6 mg/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.