Unravelling the Polytoxicology of Chlorfenapyr on Non-Target HepG2 Cells: The Involvement of Mitochondria-Mediated Programmed Cell Death and DNA Damage

Molecules. 2022 Sep 5;27(17):5722. doi: 10.3390/molecules27175722.

Abstract

Chlorfenapyr (CHL) is a type of insecticide with a wide range of insecticidal activities and unique targets. The extensive use of pesticides has caused an increase in potential risks to the environment and human health. However, the potential toxicity of CHL and its mechanisms of action on humans remain unclear. Therefore, human liver cells (HepG2) were used to investigate the cytotoxic effect and mechanism of toxicity of CHL at the cellular level. The results showed that CHL induced cellular toxicity in HepG2 cells and induced mitochondrial damage associated with reactive oxygen species (ROS) accumulation and mitochondrial calcium overload, ultimately leading to apoptosis and autophagy in HepG2 cells. Typical apoptotic changes occurred, including a decline in the mitochondrial membrane potential, the promotion of Bax/Bcl-2 expression causing the release of cyt-c into the cytosol, the activation of cas-9/-3, and the cleavage of PARP. The autophagic effects included the formation of autophagic vacuoles, accumulation of Beclin-1, transformation of LC3-II, and downregulation of p62. Additionally, DNA damage and cell cycle arrest were detected in CHL-treated cells. These results show that CHL induced cytotoxicity associated with mitochondria-mediated programmed cell death (PCD) and DNA damage in HepG2 cells.

Keywords: Chlorfenapyr; DNA damage; HepG2 cells; apoptosis; autophagy; cell cycle.

MeSH terms

  • Apoptosis*
  • Autophagy
  • DNA Damage
  • Hep G2 Cells
  • Humans
  • Membrane Potential, Mitochondrial
  • Mitochondria* / metabolism
  • Pyrethrins
  • Reactive Oxygen Species / metabolism

Substances

  • Pyrethrins
  • Reactive Oxygen Species
  • chlorfenapyr

Grants and funding

This study was supported by the National Natural Science Foundation of China (32102254) and Sichuan Science and Technology Program (2021YJ0477).