DNA damage kinetics and apoptosis in ivermectin‐treated chinese hamster ovary cells

Abstract

A comet assay was used to analyze DNA damage kinetics in Chinese hamster ovary (CHO-K1) cells induced by antiparasitic ivermectin (IVM) and the IVM-containing technical formulation Ivomec® (IVO; 1% IVM). Cells were treated with 50 µg ml(-1) IVM and IVO for 80 min, washed and re-incubated in antiparasiticide-free medium for 0-24 h until assayed using the single-cell gel electrophoresis assay (SCGE). Cell viability remained unchanged up to 3 h of incubation. After 6 h of treatment, cell survival decreased up to 75% and 79% in IVM- and IVO-treated cultures, respectively, remaining unchanged within 12-24 h after treatment. For both anthelmintics, biphasic behavior in DNA damage occurred during the incubation time. A time-dependent increase of IVM- and IVO-induced DNA damage was observed within 0 to 3 h after pulse treatment, revealed by a progressive decrease of undamaged cells and an increase in slightly damaged and damaged cells. Finally, a time-dependent decrease in IVM- and IVO-induced DNA damage was revealed by a progressive decrease of slightly damaged cells and the absence of damaged cells simultaneously with an increase in the frequency of undamaged cells during the final 18 h of incubation. Flow cytometry analysis revealed that both compounds are able to induce a marked increase in early and late apoptosis. Based on our observations, we could conclude that the decrease in DNA lesions is mostly related to IVM-induced cytotoxicity rather than attributable to a repair process.

Genotoxicity and Cytotoxicity Exerted by Pesticides in Different Biotic Matrices-An Overview of More Than a Decade of Experimental Evaluation

“…Unfortunately, the identity of the components present within the excipient formulations was not made available by the manufacturer. These final remarks are in accord with previous observations not only reported by us but also by other research groups indicating the presence of xenobiotics within the composition of the commercial formulations with genotoxic and cytotoxic effects as previously mentioned [44,46,51,[66][67][68]89,90,[125][126][127][128][129][130]. Hence, risk assessment must also consider additional genocytotoxic effects caused by the excipient/s.…”

“…Although pesticides are developed through very strict regulation processes to function with reasonable certainty and minimal impact on human health and the environment, serious concerns have been raised about health risks resulting from occupational exposure and from residues in food and drinking water [41]. Several investigations have demonstrated that the additive compounds present in pesticide commercial formulations have the ability to induce cellular toxicity, including genotoxicity and genotoxicity by themselves, separate from the active ingredient [42][43][44][45][46][47][48][49][50][51]. Accordingly, risk assessment must also consider additional toxic effects caused by the excipient(s).…”

The genotoxic effects of the imidacloprid-based insecticide formulation Glacoxan Imida on Montevideo tree frog Hypsiboas pulchellus tadpoles (Anura, Hylidae)

“…Although pesticides are developed through very strict regulation processes to function with reasonable certainty and minimal impact on human health and the environment, serious concerns have been raised about health risks resulting from occupational exposure and from residues in food and drinking water (WHO, 1990). Several investigations have demonstrated that the additive compounds present in pesticide commercial formulations have the ability to induce toxicity and cellular damage by themselves, separate from the active ingredient (Belden et al, 2010;Brühl et al, 2013;Lin and Garry, 2000;Mann and Bidwell, 1999;Molinari et al, 2013;Nikoloff et al, in press, 2012;Rayburn et al, 2005;Soloneski and Larramendy, 2010;Zeljezic et al, 2006). Hence, risk assessment must also consider additional toxic effects caused by the excipient(s).…”

Cytotoxic and genotoxic effects of abamectin, chlorfenapyr, and imidacloprid on CHOK1 cells

“…Abamectin induced single-strand DNA breaks in the rat hepatocytes (EPA 1989); there are rare studies on the genotoxicity of abamectin. Molinari et al (2009Molinari et al ( , 2013 found that ivermectin did not induce SCE in the CHO K1 cells; however, it induced single-DNA-strand breaks. Ivermectin showed genotoxic effects on the somatic cells of the mother Wister rats and higher MN frequencies in the red blood cells from the embryos' umbilical cord compared with the control (El-Ashmawy et al 2011).…”