The toxicological impact of some avermectins on human erythrocytes glutathione S-transferase enzyme

J Biochem Mol Toxicol. 2018 Oct;32(10):e22205. doi: 10.1002/jbt.22205. Epub 2018 Aug 8.

Abstract

The drugs of the class avermectins are antiparasitic agents, which are widely used in medical and agricultural fields, especially in veterinary medicine. The aim of this study was to investigate the inhibitory effects of avermectin derivatives such as abamectin, doramectin, eprinomectin, ivermectin, and moxidectin, which are used for internal and external mammalian parasites. Glutathione S-transferase (GST, E.C. 2.5.1.18) was purified from fresh human erythrocytes. The purification of the GST enzyme was performed separately by affinity chromatography with a yield of 34.81% and 117.94-fold purification. The control of the pure GST enzyme was performed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, and a single band was obtained. The IC50 values were approximately 0.31, 0.39, 0.13, 0.44, and 0.73 mM for abamectin, doramectin, eprinomectin, ivermectin, and moxidectin, and the Ki values were 0.32 ± 0.06, 0.39 ± 0.09, 0.13 ± 0.03, 0.44 ± 0.02, 0.73 ± 0.04 mM, respectively. This data revealed that the tested avermectins showed significant inhibitory effects on the GST enzyme.

Keywords: avermectin; enzyme inhibition; enzyme purification; glutathione s-transferase (GST); human erythrocyte.

MeSH terms

  • Antiparasitic Agents / toxicity
  • Chromatography, Affinity
  • Electrophoresis, Polyacrylamide Gel
  • Erythrocytes / enzymology*
  • Glutathione Transferase / antagonists & inhibitors*
  • Glutathione Transferase / blood
  • Glutathione Transferase / isolation & purification
  • Humans
  • Inhibitory Concentration 50
  • Ivermectin / analogs & derivatives*
  • Ivermectin / toxicity

Substances

  • Antiparasitic Agents
  • Ivermectin
  • avermectin
  • Glutathione Transferase