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 (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.
Molinari
G
G
Cátedra de Citología, Facultad de Ciencias Naturales y Museo, Universidad Nacional de La Plata, La Plata, Argentina.
Soloneski
S
S
Reigosa
M A
MA
Larramendy
M L
ML
D000818:Animals; D000977:Antiparasitic Agents / Q000494:pharmacology / Q000633:toxicity; D016466:CHO Cells; D049109:Cell Proliferation / Q000187:drug effects*; D006224:Cricetinae; D003412:Cricetulus; D003603:Cytotoxins / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007306:Insecticides / Q000494:pharmacology / Q000633:toxicity; D007559:Ivermectin / Q000494:pharmacology*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000494:pharmacology* / Q000633:toxicity
D000977:Antiparasitic Agents; D003603:Cytotoxins; D007306:Insecticides; D009153:Mutagens; D007559:Ivermectin