Genotoxic and cytotoxic in vitro evaluation of ivermectin and its formulation ivomec® on Aedes albopictus larvae (CCL-126™) cells

Abstract

Genotoxic effects of ivermectin (IVM) and its commercial formulation ivomec® (IVM 1.0%) were studied on Aedes albopictus larvae (CCL-126™) cells by sister chromatid exchange (SCE) and single cell gel electrophoresis (SCGE) while cytotoxicity was determined by cell-cycle progression (CCP), proliferative rate index (PRI), mitotic index (MI), 3(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and neutral red (NR) endpoints within a 1–250 µg mL⁻¹ concentration range. While IVM and ivomec® did not markedly affect SCE frequencies, these agents induced DNA-strand breaks enhancing both slightly damaged and damaged cells at 25–50 and 5–50 µg mL⁻¹ IVM and ivomec®, respectively. Both compounds exerted a delay in CCP and reduction of PRI at 10 µg mL⁻¹. Cytotoxicity was observed at concentrations higher than 25 µg mL⁻¹. A marked reduction of about 98% and 94% of MI compared to controls was noted with 25 µg mL⁻¹ of IVM and ivomec®, respectively. NR and MTT assays revealed that both compounds induced a cell growth inhibition within the 1–250 µg mL⁻¹ concentration range. Data indicated that IVM and ivomec® exert both genotoxicity and cytotoxicity in insect cells in vitro, at least in A. albopictus larvae CCL-126™ cells.

Keywords:

• comet assay
• SCE assay
• cell-cycle kinetics
• MTT assay
• neutral red assay
• mosquito cells
• cell growth inhibition

Acknowledgments

We thank M.I. Urrutia Ing. for technical assistance. This study was supported by grants the National University of La Plata (11/N493 and 11/N564), and the National Agency of Scientific and Technological Promotion (PICT 2004 no. 26116) from Argentina.