Avermectin induced DNA damage to the apoptosis and autophagy in human lung epithelial A549 cells

Ecotoxicol Environ Saf. 2021 Jun 1:215:112129. doi: 10.1016/j.ecoenv.2021.112129. Epub 2021 Mar 16.

Abstract

Avermectin (AVM), as a biological insecticide, is widely used in agriculture and forestry production globally. However, inhalation of AVM may pose a risk, and the lung is the direct target, but the cytotoxicity of AVM on human lung cells is still unclear. Here, we attempted to elucidate the cytotoxic effect and molecular mechanism of AVM on human lung A549 cells. The results indicated that AVM inhibits cell proliferation, and enhances programmed cell death (apoptosis and autophagy). In addition, we found the AVM-treated cells showed an obvious drop in mitochondrial membrane potential and LC3-I/II, increased ROS production, DNA double-strand breaks, caspase-3/9 activated, PARP cleaved, cytochrome c and Bax/Bcl-2 content rise. The results showed that AVM induced mitochondria-related apoptosis and autophagy in lung A549 cells. These results indicate that AVM can pose a potential threat to human health by inducing DNA damage and programmed cell death.

Keywords: Avermectin; Cytotoxicity; DNA damage; Human A549 cells; Programmed cell death.

MeSH terms

  • A549 Cells
  • Apoptosis / drug effects
  • Autophagy / drug effects
  • Cell Proliferation / drug effects
  • Cytochromes c / metabolism
  • DNA Damage / drug effects
  • Humans
  • Insecticides / toxicity*
  • Ivermectin / analogs & derivatives*
  • Ivermectin / toxicity
  • Lung / metabolism
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects
  • Proto-Oncogene Proteins c-bcl-2

Substances

  • BCL2 protein, human
  • Insecticides
  • Proto-Oncogene Proteins c-bcl-2
  • Ivermectin
  • avermectin
  • Cytochromes c