Cytotoxic effects of Avermectin on human HepG2 cells in vitro bioassays

Environ Pollut. 2017 Jan;220(Pt B):1127-1137. doi: 10.1016/j.envpol.2016.11.022. Epub 2016 Nov 13.

Abstract

Avermectin (AVM) has been widely used in agriculture and animal husbandry based on its broad spectrum of effective anthelmintic activity and specificity targets. However, AVM induction of cytotoxicity in human liver is largely unknown. In this study, we investigate the cytotoxic effects of AVM on HepG2 cells in vitro. The results revealed that AVM inhibited the viability of HepG2 cells and enhanced apoptosis. Established assays of cytotoxicity were performed to characterize the mechanism of AVM toxicity on HepG2 cells. Typical apoptosis morphological changes were shown in AVM-treatment cells including chromatin condensation and DNA fragmentation. We demonstrated that AVM-induced apoptosis of HepG2 cells were mediated by generated ROS. Moreover, a decrease in mitochondrial membrane potential (MMP) and up-regulating the Bax/Bcl-2 ratio, resulted in a release of cytochrome-c as well as activation of caspase-9/-3. In conclusion, our experimental results show that AVM has a potential threat to human health which may be induce apoptosis of human hepatocyte cells via caspase-dependent mitochondrial pathways.

Keywords: Avermectin; Cytotoxic effects; Environmental toxicity; HepG2 cells; Mitochondrial-mediated apoptosis; Pesticide.

MeSH terms

  • Animals
  • Anthelmintics / toxicity
  • Apoptosis / drug effects
  • Biological Assay*
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Chromatin / drug effects
  • Chromatin / metabolism
  • DNA Fragmentation / drug effects
  • Environmental Pollutants / toxicity
  • Hep G2 Cells
  • Humans
  • Ivermectin / analogs & derivatives*
  • Ivermectin / toxicity
  • Liver / cytology
  • Liver / drug effects
  • Membrane Potential, Mitochondrial / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / metabolism
  • bcl-2-Associated X Protein / metabolism

Substances

  • Anthelmintics
  • BCL2 protein, human
  • Chromatin
  • Environmental Pollutants
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • bcl-2-Associated X Protein
  • Ivermectin
  • avermectin
  • Caspase 3
  • Caspase 9