Mechanism of arsenic-induced liver injury in rats revealed by metabolomics and ionomics based approach
Description
Arsenic (As) is an environmental toxicant and human carcinogen, long-term exposure to As can lead to varying degrees of liver injury. In this study, the liver injury model of As poisoned Sprague-Dawley (SD) rats was established, and the potential mechanism was investigated by metabonomics and ionomics. A total of 164 differential expressed metabolites (DEMs) were identified between the As poisoned group and the control group, which mainly involved in nicotinate and nicotinamide metabolism, steroid hormone biosynthesis, taurine and hypotaurine metabolism, and porphyrin metabolism. The levels of 10 ions were significantly increased in As poisoned group, including As, bismuth (Bi), cadmium (Cd), mercury (Hg), manganese (Mn), rubidium (Rb), antimony (Sb), strontium (Sr), uranium(U), and zinc (Zn), in contrast, the levels of lead (Pb) and thallium (TI) were significantly decreased. Spearman correlation analysis showed that As, Cd, Hg and Pb were negatively correlated with androstenedione, protoporphyrinogen IX and estriol, whereas As and Mn was positively correlated with progesterone (PROG), Cd was positively correlated with NAD+ and 3-Sulfino-L-alanine. There are sex differences in changes in metabolites and ions levels. Male and female rats shared 60 DEMs and 2 pathways (steroid hormone biosynthesis and porphyrin metabolism pathway). The levels of As, Cd, Hg, and Sr were significantly changed in both male and female rats. In both female and male rats, As was positively correlated with PROG, and Cd was positively correlated with coproporphyrin III. The results of this study provide new insights to elucidate the mechanism of As-induced liver injury in rats.