Short-term exposure to antimony induces hepatotoxicity and metabolic remodeling in rats

作者：Wen Gu, Ruifang Pang, Yuanyuan Chen, Fuchang Deng, Miao Zhang, Zijin Shao, Shuyi Zhang, Huawei Duan, Song Tang · 发表于：Ecotoxicology and Environmental Safety · 年份：2023 · DOI：10.1016/j.ecoenv.2023.114852 · 被引用次数：16 · 研究领域：Arsenic contamination and mitigation、Selenium in Biological Systems、Fluoride Effects and Removal

Antimony (Sb) poses a significant threat to human health due to sharp increases in its exploitation and application globally, but few studies have explored the pathophysiological mechanisms of acute hepatotoxicity induced by Sb exposure. We established an in vivo model to comprehensively explore the endogenous mechanisms underlying liver injury induced by short-term Sb exposure. Adult female and male Sprague-Dawley rats were orally administrated various concentrations of potassium antimony tartrate for 28 days. After exposure, the serum Sb concentration, liver-to-body weight ratio, and serum glucose levels significantly increased in a dose-dependent manner. Body weight gain and serum concentrations of biomarkers of hepatic injury (e.g., total cholesterol, total protein, alkaline phosphatase, and the aspartate aminotransferase/alanine aminotransferase ratio) decreased with increasing Sb exposure. Through integrative non-targeted metabolome and lipidome analyses, alanine, aspartate, and glutamate metabolism; phosphatidylcholines; sphingomyelins; and phosphatidylinositols were the most significantly affected pathways in female and male rats exposed to Sb. Additionally, correlation analysis showed that the concentrations of certain metabolites and lipids (e.g., deoxycholic acid, N-methylproline, palmitoylcarnitine, glycerophospholipids, sphingomyelins, and glycerol) were significantly associated with hepatic injury biomarkers, indicating that metabolic remodeling may be involved ...