Characterization of Hepatotoxic Effects Induced By Ivermectin In Zebrafish Larvae And Human Lo2 Cells

Ivermectin (IVM) is a highly effective and broad-spectrum biopesticide characterized by high fat solubility and easy residues in animal food, but its specific effects on the liver are unknown. We employed zebrafish and LO2 cells as experimental models to conduct a comprehensive study on the impact of IVM on the liver. Our results showed that IVM caused delayed yolk sac absorption and hepatic lipid accumulation in zebrafish larvae by inducing hepatic lipid synthesis, lipid catabolism, and abnormal lipid transport. IVM triggered an abnormal buildup of endogenous ROS and altered antioxidant enzyme activities in zebrafish larvae. The accumulation of lipids in the liver made it vulnerable to oxidative stress, which subsequently led to liver damage. This was evidenced by pronounced vacuolization of liver cells and changes in liver morphology. In addition, we obtained similar experimental results in LO2 cells and further explored the molecular mechanism of IVM induced abnormal lipid metabolism. The experimental outcomes indicated that IVM ultimately disrupted hepatic lipid metabolism by activating the AMPK/PPAR-α pathway, a process that subsequently resulted in liver injury. This study offers significant insights into the hepatotoxic effects of IVM, highlighting the potential health risks it poses to liver function.

Note:
Funding declaration: This work was supported by the National Key Research and Development Plan (Grant No. 2022YFD1700502), Shanghai Agricultural Science and Technology Innovation Project (T2023205) and the Fundamental Research Funds for the Central Universities.

Conflict of Interests: There are no conflicts to declare.

Ethical Approval: All experiments were performed in strict compliance with the guidelines established by the Animal Care Committee of East China University of Science and Technology (approval number #2006272).

Keywords: Ivermectin, Hepatotoxicity, Mitochondrial damage, LO2 cells, zebrafish larvae

Suggested Citation: Suggested Citation

Li, Shoulin and wu, mengqi and Xiong, Shouqian and Liu, Su and Xu, Wenping and Cheng, Jiagao and Tao, Liming and Li, Zhong and Zhang, Yang, Characterization of Hepatotoxic Effects Induced By Ivermectin In Zebrafish Larvae And Human Lo2 Cells. Available at SSRN: https://ssrn.com/abstract=5084353 or http://dx.doi.org/10.2139/ssrn.5084353