2. Academic Validation
  3. Characterization of hepatotoxic effects induced by pyraclostrobin in human HepG2 cells and zebrafish larvae

Characterization of hepatotoxic effects induced by pyraclostrobin in human HepG2 cells and zebrafish larvae

  • Chemosphere. 2023 Nov:340:139732. doi: 10.1016/j.chemosphere.2023.139732.
Mengqi Wu 1,  Jinhao Bian 2,  Shuang Han 3,  Cheng Zhang 4,  Wenping Xu 5,  Liming Tao 6,  Zhong Li 7,  Yang Zhang 8
Affiliations

Affiliations

  • 1 Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, PR China. Electronic address: [email protected].
  • 2 Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, PR China. Electronic address: [email protected].
  • 3 Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, PR China. Electronic address: [email protected].
  • 4 Department of Pathology, UT Southwestern Medical Center, Dallas, TX, 75390, United States. Electronic address: [email protected].
  • 5 Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, PR China. Electronic address: [email protected].
  • 6 Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, PR China. Electronic address: [email protected].
  • 7 Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, PR China; State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, PR China. Electronic address: [email protected].
  • 8 Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, PR China. Electronic address: [email protected].
PMID: 37549743 DOI: 10.1016/j.chemosphere.2023.139732
Abstract

Pyraclostrobin is a highly effective and broad-spectrum strobilurin fungicide. With the widespread use of pyraclostrobin to prevent and control crop diseases, its environmental pressure and potential safety risks to humans have attracted much attention. Herein, the toxicological risks of pyraclostrobin toward HepG2 cells and the mechanisms of intoxication in vitro were investigated. The liver toxicity of pyraclostrobin in zebrafish larvae was also evaluated. It was found that pyraclostrobin induced DNA damage and Reactive Oxygen Species generation in HepG2 cells, indicating the potential genotoxicity of pyraclostrobin. The results of fluorescent staining experiments and the expression of cytochrome c, Bcl-2 and Bax demonstrated that pyraclostrobin induced mitochondrial dysfunction, resulting in cell Apoptosis. Monodansylcadaverine staining and Autophagy marker-related proteins LC3, p62, Beclin-1 protein expression showed that pyraclostrobin promoted cell Autophagy. Furthermore, immunoblotting analysis suggested that pyraclostrobin induced Autophagy accompanied with activation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/mTOR signaling pathway. Visualization of zebrafish liver and oil red staining indicated that pyraclostrobin could induce liver degeneration and liver steatosis in zebrafish. Collectively, these results help to better understand the hepatotoxicity of pyraclostrobin and provide a scientific basis for its safe applications and risk control.

Keywords

Autophagy; HepG2 cells; Hepatotoxicity; Mitochondrial damage; Pyraclostrobin; Zebrafish.

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