Toosendanin triggered hepatotoxicity in zebrafish via inflammation, autophagy, and apoptosis pathways
Meng Sun1, Qing Liu2, Qiuxia Liang1
1Biology 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.
Abstract:
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.
Insights
Toosendanin (TSN) causes liver injury in zebrafish by affecting inflammation, autophagy, and apoptosis. This study reveals mechanisms of TSN-induced hepatotoxicity, important for understanding its safety profile.
Area of Science:
- Toxicology
- Pharmacology
- Zebrafish models
Background:
- Toosendanin (TSN) from Toosendan Fructus shows anti-tumor potential.
- TSN is suspected to be hepatotoxic, but mechanisms are unclear.
Purpose of the Study:
- Evaluate TSN hepatotoxicity in zebrafish.
- Investigate the roles of inflammation, autophagy, and apoptosis in TSN-induced liver injury.
Main Methods:
- Zebrafish were treated with TSN at nonlethal concentrations.
- Liver morphology, ALT/AST levels, and gene expression were analyzed.
- Time- and dose-dependent effects were assessed.
Main Results:
- TSN reduced liver area and fluorescence intensity in a time- and dose-dependent manner.
- Increased ALT and AST levels, cytoplasmic vacuolation, and nuclear shrinkage were observed.
- Gene expression analysis indicated involvement of inflammation, autophagy, and apoptosis pathways.
Conclusions:
- TSN induces liver injury in zebrafish.
- Inflammation, autophagy, and apoptosis are key mechanisms in TSN-induced hepatotoxicity.
