Zhang Sheng, Li Chao, Feng Tingting, Cao Shuai, Zhou Heng, Li Limin, Hu Qing, Mao Xiuhong, Ji Shen
Tianjin University of Traditional Chinese Medicine, Tianjin, China.
NMPA Key Laboratory for Quality Control of Traditional Chinese Medicine, Shanghai Institute for Food and Drug Control, Shanghai, China.
Front Pharmacol. 2021 Aug 23;12:706249. doi: 10.3389/fphar.2021.706249. eCollection 2021.
Realgar has been used as a type of mineral drug that contains arsenic for thousands of years. Previous studies have shown that Realgar-induced acute kidney injury is associated with abnormal metabolism, but the underlying mechanism is poorly understood. The aim of this study is to investigate the metabolic changes in serum and kidney tissues of mice exposed to Realgar by using a metabolomic approach and explore the molecular mechanisms of acute kidney injury induced by Realgar. Forty mice were randomly divided into four groups: Control group, 0.5-, 1.0, and 2.0 g/kg Realgar group. After 1 week, the body weight and kidney weight of the mice were measured. The serum and kidney samples were used for LC-MS spectroscopic metabolic profiling. Principal component analysis (PCA), correlation analysis, and pathway analysis were used to detect the nephrotoxic effects of Realgar. Body weight decreased significantly in the 2.0 g/kg group, and the kidney weight index also showed a dose-dependent increase in Realgar. The PCA score plot showed the serum and kidney tissue metabolic profile of mice exposed to 2.0 g/kg Realgar separated from the control group, while the lower-doses of 0.5 g/kg and 1.0 g/kg Realgar shown a similar view to the Control group. Thirty-three metabolites and seventeen metabolites were screened and identified in the serum and kidney of mice in a dose-dependent manner. respectively. Correlation analysis showed a strong correlation among these metabolites. Amino acid metabolism, lipid metabolism, glutathione metabolism, and purine metabolism pathways were found to be mainly associated with Realgar nephrotoxicity. This work illustrated the metabolic alterations in Realgar-induced nephrotoxic mice through a metabolomic approach.
雄黄作为一种含砷的矿物药已被使用了数千年。先前的研究表明，雄黄诱导的急性肾损伤与代谢异常有关，但其潜在机制尚不清楚。本研究的目的是采用代谢组学方法研究暴露于雄黄的小鼠血清和肾组织中的代谢变化，并探讨雄黄诱导急性肾损伤的分子机制。40只小鼠随机分为四组：对照组、0.5 g/kg、1.0 g/kg和2.0 g/kg雄黄组。1周后，测量小鼠的体重和肾脏重量。血清和肾脏样本用于液相色谱-质谱光谱代谢谱分析。采用主成分分析（PCA）、相关性分析和通路分析来检测雄黄的肾毒性作用。2.0 g/kg组体重显著下降，肾脏重量指数也显示出雄黄剂量依赖性增加。PCA得分图显示，暴露于2.0 g/kg雄黄的小鼠血清和肾组织代谢谱与对照组分离，而较低剂量的0.5 g/kg和1.0 g/kg雄黄组与对照组相似。分别在小鼠血清和肾脏中以剂量依赖性方式筛选并鉴定出33种代谢物和17种代谢物。相关性分析表明这些代谢物之间存在强相关性。发现氨基酸代谢、脂质代谢、谷胱甘肽代谢和嘌呤代谢途径主要与雄黄肾毒性有关。这项工作通过代谢组学方法阐明了雄黄诱导肾毒性小鼠的代谢改变。
