Mechanism of arsenic-induced liver injury in rats revealed by metabolomics and ionomics based approach

Arsenic (As) is an environmental toxicant and human carcinogen, and long-term exposure to As can lead to varying degrees of liver injury. In order to futher explore the mechanism of As-induced liver injury in rats, a rat model of As poisoned was established in this study, and metabolomics and ionomics methods were applied to study the differences of liver metabolites and ion concentrations between As poisoned rats. By metabolomic analysis, a total of 164 differentially expressed metabolites (DEMs) were identified between the As poisoned group and the Contrl(Ctrl) group, in which metabolic pathways such as nicotinate and nicotinamide metabolism, steroid hormone biosynthesis, and taurine and hypotaurine metabolism were significantly enriched. Ionomics results showed that ten ions were elevated in the As poisoned group, including As, cadmium (Cd), mercury (Hg), and manganese (Mn), while lead (Pb) and thallium (Tl) were reduced (p < 0.05). Spearman Correlation analysis of DEMs and differentially ions showed that As, Cd, Hg and Pb were negatively correlated with androstenedione, protoporphyrinogen and estriol, while As was positively correlated with progesterone, Cd and nicotinamide adenine dinucleotide (NAD+), Mn and 5-L-glutamyltaurine. This study revealed the changes in liver metabolites and ions level in As poisoned rats, as well as the relationship between them and the potential mechanisms of As induced liver injury, among them, the steroid hormone biosynthesis pathway plays an important role in arsenic hepatotoxicity.