Exposure to environmental concentrations of natural pyrethrins induces hepatotoxicity: Assessment in HepG2 cell lines and zebrafish models

Natural pyrethrins are one variety of botanical pesticide, and are commonly used in organic and ecological agriculture. However, the hepatotoxicity of natural pyrethrins is unknown. In this study, the impact of natural pyrethrins on human HepG2 cells, which are prominent cell model for toxic-induced hepatotoxicity evaluations, was investigated in accordance with the ROS production and the mechanism of DNA damage and repair. And we report the liver toxicity of natural pyrethrins in zebrafish. Our result revealed a significant increase in ROS production, suggesting oxidative stress. Besides, the most notable genotoxic effect of oxidation-induced DNA damage was observed for natural pyrethrins, as detected by neutral comet assay and γH2AX/8-oxoG staining. As revealed by the results, oxidative DNA damage is responsible for the cytotoxic exposure of natural pyrethrins to HepG2 cells in humans. The observed damage is chronic toxicity, which may cause irreversible DNA damage and more severe toxic effects on human HepG2 cells. This can account for the complicated response to DNA impairment. Visual observations of zebrafish liver and oil red staining also demonstrated that natural pyrethrins induced liver degeneration, liver size changes and liver steatosis in zebrafish. In conclusion, the health of humans can be endangered by natural pyrethrins as a result of hepatotoxicity.