In vitro genotoxic and cytotoxic effects of ivermectin and its formulation ivomec® on Chinese hamster ovary (CHO_(K1) ) cells

摘要

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), prolif-erative replication index (PRI), 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and neutral red (NR)] bioassays within the 1.0-250 μg/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 μg/ml. In ivomec~®-treated cells, while an increase in slightly damaged cells was induced with 5.0-50.0 μg/ml, the damaged and undamaged cells increased and decreased only with 50.0μg/ml. Both compounds exerted a delay in CCP and a reduction in PRI when 25.0 μg/ml was employed whereas cytotoxicity was observed at higher concentration than 50.0 μg/ml. No Ml alteration was observed with 1.0-10.0 and 1.0-5.0 μg/ml of IVM and ivomec~®, respectively. A concentration-related trend to an increase in MI was achieved within 1.0-10.0 μg/ml. An increase in the MI was induced in 10.0 μg/ml ivomec~®-treated cultures. A marked reduction of about 89% and 62% in regard to controls was observed with 25.0 μg/ml of IVM and ivomec~®, respectively. NR and MTT assays revealed a cell growth inhibition when 0.25-250.0 μg/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 CHOki cells.