In vitro and in silico analyses reveal the toxicity of metolachlor to grass carp hepatocytes and the antagonism of melatonin1

Qianru Chi, Yu Xia, Dongliu Luo, Lixiu Zhu, Xiuqin Yang, Shu Li

Research output: Contribution to journalArticlepeer-review


Due to the widespread use of metolachlor (MET), the accumulation of MET and its metabolites in the environment has brought serious health problems to aquatic organisms. At present, the toxicity of MET on the physiological metabolism of aquatic animals mainly focused on the role of enzymes. There is still a lack of research on the molecular mechanisms of MET hepatotoxicity, especially on antagonizing MET toxicity. Therefore, this study focuses on grass carp hepatocytes (L8824 cells) closely related to toxin accumulation. By establishing a MET exposed L8824 cells model, it is determined that MET exposure induces pyrolytic inflammation of L8824 cells. Subsequent mechanistic studies found that MET exposure induces pyroptosis in L8824 cells through mitochondrial dysfunction, and siCaspase-1 inhibits the MET induced ROS production, suggesting a regulation of ROS-NLRP3- Caspase-1 pyroptotic inflammation cycling center in MET induced injury to L8824 cells. Molecular docking revealed a strong binding energy between melatonin (MT) and Caspase-1. Finally, a model of L8824 cells with MT intervention in MET exposure was established. MT can antagonize the pyroptosis induced by MET exposure in L8824 cells by targeting Caspase-1, thereby restoring mitochondrial function and inhibiting the ROS-pyroptosis cycle. This study discovered targets and mechanisms of MT regulating pyroptosis in MET exposed-L8824 cells, and the results are helpful to provide new targets for the design of MET antidotes.

Original languageEnglish
Article number105930
JournalPesticide Biochemistry and Physiology
Publication statusPublished - Jun 2024
Externally publishedYes


  • Grass carp hepatocytes
  • Melatonin
  • Metolachlor
  • Mitochondrial dysfunction
  • Pyroptosis


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