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

The effects of ivermectin (IVM) and its commercial formulation ivomec (R) (IVM 1.0%) were Studied on Chinese hamster ovary (CHOK1) 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 mu g/ml concentration-range. While IVM and ivomec (R) 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 mu g/ml. In ivomec (R)-treated cells, while an increase in slightly damaged cells was induced with 5.0-50.0 mu g/ml, the damaged and undamaged cells increased and decreased only with 50.0 mu g/ml. Both compounds exerted a delay in CCP and a reduction in PRI when 25.0 mu g/ml was employed whereas cytotoxicity was observed at higher concentration than 50.0 mu g/ml. No MI alteration was observed with 1.0-10.0 and 1.0-5.0 mu g/ml of IVM and ivomec (R), respectively. A concentration-rela red trend to an increase in MI was achieved within 1.0-10.0 mu g/ml. An increase in the MI was induced in 10.0 mu g/ml ivomec (R)-treated cultures. A marked reduction of about 89% and 62% in regard to controls was observed with 25.0 mu g/ml of IVM and ivomec (R), respectively. NR and MTT assays revealed a cell growth inhibition when 0.25-250.0 mu g/ml of both compounds was employed. The results highlighted that IVM and ivomec (R) exert both genotoxicity and cytotoxicity in mammalian cells in vitro, at least in CHOK1 cells. (C) 2008 Elsevier B.V. All rights reserved.