Xu Can, Wang Yingfeng, Rezeng Caidan, Zhang Lan, Zhao Baosheng, Wang Xia, Wu Xiuyuan, Li Zhongfeng, Chen Jianxin
Department of Chemistry, Capital Normal University No. 105, Xisanhuanbeilu, Haidian District Beijing 100048 PR China
College of Pharmacy, Qinghai Nationalities University No. 3 Bayizhong Road Xining 810000 PR China.
RSC Adv. 2018 Nov 8;8(66):37652-37664. doi: 10.1039/c8ra07058j. eCollection 2018 Nov 7.
Renqing Changjue (RQCJ), a precious Traditional Tibetan Medicine (TTM), has been widely used in the management of diseases of the digestive system, toxinosis and pyreticosis. However, in the formula, a significant level of heavy metals, which are potential toxic elements, are present. Therefore, it is important to assess the toxicity of RQCJ dynamically and holistically. In the present study, a H NMR metabolomics approach and inductively coupled plasma mass spectrometry (ICP-MS) were implemented to analyze the samples of liver, kidney and spleen from rats treated with RQCJ. The results revealed that 9 metabolites in the liver, 13 metabolites in the kidney and 16 metabolites in the spleen were significantly altered, which suggest that disturbances in TCA cycle, amino acid metabolism, energy metabolism and oxidative stress are produced by successive administration of RQCJ over 15 days. Complemented by histopathology and biochemical assay, the trends of the metabolite levels indicate that RQCJ caused tissue injury to a certain extent, which was evidenced by the high levels of As and Hg in the tissue. The toxic effects of RQCJ were alleviated in liver and kidney during the recovery period, and RQCJ may cause long-term damage in spleen. These findings provide a significant experimental proof on the estimated safety and valuable information about the metabolism of RQCJ, which will be valuable in determining the health risks of the drug.
仁青常觉（RQCJ）是一种珍贵的藏药，已被广泛用于治疗消化系统疾病、中毒症和热病。然而，该配方中存在大量重金属，这些都是潜在的有毒元素。因此，动态、全面地评估仁青常觉的毒性很重要。在本研究中，采用核磁共振氢谱代谢组学方法和电感耦合等离子体质谱法（ICP-MS）分析了用仁青常觉处理的大鼠的肝脏、肾脏和脾脏样本。结果显示，肝脏中有9种代谢物、肾脏中有13种代谢物、脾脏中有16种代谢物发生了显著变化，这表明连续15天给予仁青常觉会导致三羧酸循环、氨基酸代谢、能量代谢和氧化应激紊乱。通过组织病理学和生化分析补充，代谢物水平的趋势表明仁青常觉在一定程度上造成了组织损伤，组织中砷和汞的高含量证明了这一点。恢复期肝脏和肾脏中仁青常觉的毒性作用有所减轻，而仁青常觉可能会对脾脏造成长期损害。这些发现为仁青常觉的估计安全性提供了重要的实验证据，并提供了有关其代谢的有价值信息，这对于确定该药物的健康风险将是有价值的。
