In vitro genotoxic and cytotoxic effects of ivermectin and its formulation ivomec on Chinese hamster ovary (CHOK1) cells

J Hazard Mater. 2009 Jun 15;165(1-3):1074-82. doi: 10.1016/j.jhazmat.2008.10.083. Epub 2008 Oct 31.

Abstract

The effects of ivermectin (IVM) and its commercial formulation ivomec (IVM 1.0%) were studied on Chinese hamster ovary (CHO(K1)) cells by several genotoxicity [sister chromatid exchange (SCE) and single cell gel electrophoresis (SCGE)] and cytotoxicity [cell-cycle progression (CCP), mitotic index (MI), proliferative replication index (PRI), 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and neutral red (NR)] bioassays within the 1.0-250 microg/ml concentration-range. While IVM and ivomec did not modified SCE frequencies, they induced DNA-strand breaks revealed by SCGE. An enhancement of slightly damaged cells and a decrease in undamaged cells were observed in IVM-treated cultures with 5.0-50.0 microg/ml. In ivomec((R))-treated cells, while an increase in slightly damaged cells was induced with 5.0-50.0 microg/ml, the damaged and undamaged cells increased and decreased only with 50.0 microg/ml. Both compounds exerted a delay in CCP and a reduction in PRI when 25.0 microg/ml was employed whereas cytotoxicity was observed at higher concentration than 50.0 microg/ml. No MI alteration was observed with 1.0-10.0 and 1.0-5.0 microg/ml of IVM and ivomec, respectively. A concentration-related trend to an increase in MI was achieved within 1.0-10.0 microg/ml. An increase in the MI was induced in 10.0 microg/ml ivomec-treated cultures. A marked reduction of about 89% and 62% in regard to controls was observed with 25.0 microg/ml of IVM and ivomec, respectively. NR and MTT assays revealed a cell growth inhibition when 0.25-250.0 microg/ml of both compounds was employed. The results highlighted that IVM and ivomec exert both genotoxicity and cytotoxicity in mammalian cells in vitro, at least in CHO(K1) cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiparasitic Agents / pharmacology
  • Antiparasitic Agents / toxicity
  • CHO Cells
  • Cell Proliferation / drug effects*
  • Cricetinae
  • Cricetulus
  • Cytotoxins / pharmacology*
  • DNA Damage / drug effects*
  • Dose-Response Relationship, Drug
  • Insecticides / pharmacology
  • Insecticides / toxicity
  • Ivermectin / pharmacology*
  • Mutagenicity Tests
  • Mutagens / pharmacology*
  • Mutagens / toxicity

Substances

  • Antiparasitic Agents
  • Cytotoxins
  • Insecticides
  • Mutagens
  • Ivermectin