Guizhou University of Traditional Chinese Medicine, Guiyang, China.
Basic Clin Pharmacol Toxicol. 2021 Jul;129(1):61-71. doi: 10.1111/bcpt.13585. Epub 2021 Apr 22.
Cantharidin (CTD) is a promising anticancer drug; however, its dosage is limited by hepatotoxicity. We previously showed that Astragalus polysaccharides (APS) effectively improved chemical liver injury. In this study, we established a CTD-induced subacute liver injury mouse model and examined the effects of APS on weight, liver indexes, histopathology, serum biochemical indexes and liver metabolism. Compared with the control group, mice in the CTD model group had obvious liver damage, which was partially prevented by APS. Metabolomics demonstrated that CTD caused liver damage mainly by regulating glycerophospholipid metabolism, ABC transporter pathways and choline metabolism in cancer in vivo. APS regulated primary bile acid biosynthesis and glycerophospholipid metabolism, thus decreasing the liver damage caused by CTD. This study revealed the protective mechanism of APS against CTD-induced liver injury from the perspective of metabolomics. The results provide an important basis for analysing the mechanism of CTD-induced liver toxicity and for assessing clinical treatment options to reduce CTD liver toxicity.
斑蝥素（CTD）是一种很有前途的抗癌药物；然而，其剂量受到肝毒性的限制。我们之前的研究表明，黄芪多糖（APS）能有效改善化学性肝损伤。在本研究中，我们建立了 CTD 诱导的亚急性肝损伤小鼠模型，研究了 APS 对体重、肝指数、组织病理学、血清生化指标和肝脏代谢的影响。与对照组相比，CTD 模型组小鼠肝损伤明显，APS 可部分预防。代谢组学研究表明，CTD 主要通过调节体内甘油磷脂代谢、ABC 转运蛋白途径和胆碱代谢引起肝损伤。APS 调节初级胆汁酸生物合成和甘油磷脂代谢，从而减轻 CTD 引起的肝损伤。本研究从代谢组学的角度揭示了 APS 对 CTD 诱导肝损伤的保护机制。该研究结果为分析 CTD 诱导肝毒性的机制以及评估减少 CTD 肝毒性的临床治疗方案提供了重要依据。
