Metabolomicsand arsenic-based liver injury methods reveal the mechanism of arsenic-induced liver injury in rats project

Arsenic (As) is an environmental poison and human carcinogen that poses a serious threat to human health, and long-term exposure to arsenic can cause liver damage. In order to explore the mechanism of As-induced liver injury in rats, a rat model of As poisoning was established, and metabolomics and ionomics methods were used to study the differences in liver metabolites and ion concentrations between As poisoned and control (Ctrl) rats. Through metabolomic analysis, 164 differentially expressed metabolites (DEMs) were identified in the As poisoning group and Ctrl group, among which nicotinate and nicotinamide metabolism, steroid hormone biosynthesis, taurine and subtaurine metabolism were significantly enriched. Arsenomics results showed that arsenic, cadmium (Cd), mercury (Hg) and manganese (Mn) were elevated in the arsenic poisoning group, and lead (Pb) and thallium (Tl) (<i>p </i>Correlation analysis of DEMs with differential ions showed that As, Cd and Hg were negatively correlated with androstenedione and estriol, while As was negatively correlated with progesterone (PROG), Cd and nicotinamide adenine dinucleotide (NAD). ⁺), Mn and 5-L-glutamyl taurine were positively correlated. This study revealed the changes of liver metabolites and ion levels in rats with As toxicity model, and their relationship with the underlying mechanism of As-induced liver injury, which provided a reference for the study of the mechanism of As-induced hepatotoxicity.

砷（Arsenic, As）是一种环境毒物与人类致癌物，对人体健康构成严重威胁，长期接触砷可引发肝损伤。为探究砷诱导的大鼠肝损伤机制，本研究建立了砷中毒大鼠模型，并采用代谢组学（Metabolomics）与离子组学（Ionomics）方法，比较分析砷中毒组与对照（Control, Ctrl）大鼠的肝脏代谢物及离子浓度差异。通过代谢组学分析，本研究在砷中毒组与对照组中共鉴定出164种差异表达代谢物（Differentially Expressed Metabolites, DEMs），其中烟酸与烟酰胺代谢、类固醇激素生物合成、牛磺酸与亚牛磺酸代谢通路显著富集。砷组学（Arsenomics）分析结果显示，砷中毒组的砷、镉（Cadmium, Cd）、汞（Mercury, Hg）与锰（Manganese, Mn）水平均升高，铅（Lead, Pb）与铊（Thallium, Tl）的差异具有统计学意义（p < 0.05）。差异表达代谢物与差异离子的相关性分析表明：砷、镉与汞均与雄烯二酮、雌三醇呈负相关；砷与孕酮（Progesterone, PROG）、镉呈负相关，而烟酰胺腺嘌呤二核苷酸（Nicotinamide Adenine Dinucleotide, NAD+）、锰与5-L-谷氨酰牛磺酸呈正相关。本研究阐明了砷中毒模型大鼠的肝脏代谢物与离子水平变化，及其与砷诱导肝损伤潜在机制的关联，为砷诱导肝毒性的机制研究提供了参考依据。