Thiophanate-methyl induces severe hepatotoxicity in zebrafish

Thiophanate-methyl (TM) is widely used all over the world and is a typical example of pesticide residues, which can be detected in the soil, and even in vegetables and fruits. However, the molecular mechanisms underlying the hepatotoxicity of TM are not well understood. In this study, we utilized zebrafish to comprehensively evaluate the hepatotoxicity of TM and explore how the molecular mechanisms of hepatotoxicity are induced. The zebrafish larvae were exposed in 6.25, 12.5 and 25 mg/L TM from 72 to 144 hpf, while the adults were exposed in 2, 4 and 6 mg/L TM for 28 days. Here, we found that 12.5 and 25 mg/L TM induces specifically serious hepatotoxicity but not the toxicity of other organs in zebrafish larvae and adults. Moreover, it might triggered hepatotoxicity by activating the caspase-3 through apoptotic pathways and oxidative stress in zebrafish. Subsequently, this resulted in a metabolic imbalance in the zebrafish's liver. In conclusion, our results disclosed the fact that TM may induce severe hepatotoxicity by mediating activation of caspase-3 and oxidative stress in zebrafish.