Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China; School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.
Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China; School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.
Comp Biochem Physiol C Toxicol Pharmacol. 2021 Dec;250:109171. doi: 10.1016/j.cbpc.2021.109171. Epub 2021 Aug 26.
Toosendanin (TSN) is a crucial component from Toosendan Fructus with a promising anti-tumor capacity. It is also the primary suspect hepatotoxic component of Toosendan Fructus. However, the mechanisms underlying TSN-induced liver injury are still largely unknown. In present study, we evaluated the hepatotoxicity of TSN on zebrafish and explored the role of inflammation, autophagy, and apoptosis in TSN-induced hepatotoxicity. We found that TSN treatment decreased the area and fluorescence intensity of zebrafish liver in time- and dose-dependent manners at nonlethal concentrations. The ALT and AST activities were increased after TSN treatment. Severe cytoplasmic vacuolation and nuclear shrank were found in the liver of TSN-treated zebrafish. The expression profile of genes demonstrated that inflammation, autophagy and apoptosis pathways were involved in TSN-induced hepatotoxicity. Our study demonstrated for the first time that TSN treatment gave rise to liver injury in zebrafish, and inflammation, autophagy, apoptosis played a role in TSN-induced hepatotoxicity.
川楝素（TSN）是川楝果实中的重要成分，具有很好的抗肿瘤能力。它也是川楝果实中主要的潜在肝毒性成分。然而，TSN 诱导肝损伤的机制在很大程度上尚不清楚。在本研究中，我们评估了 TSN 对斑马鱼的肝毒性，并探讨了炎症、自噬和细胞凋亡在 TSN 诱导肝毒性中的作用。我们发现，在非致死浓度下，TSN 以时间和剂量依赖的方式降低了斑马鱼肝脏的面积和荧光强度。TSN 处理后 ALT 和 AST 活性增加。在 TSN 处理的斑马鱼肝脏中发现严重的细胞质空泡化和核皱缩。基因表达谱表明，炎症、自噬和细胞凋亡途径参与了 TSN 诱导的肝毒性。我们的研究首次表明，TSN 处理导致斑马鱼肝脏损伤，炎症、自噬和细胞凋亡在 TSN 诱导的肝毒性中发挥作用。
