Co-administration of vitamin E and selenium in vivo and in vitro ameliorates the toxic effects caused by ivermection and doramectin

Abstract

Avermectins are used in animals and humans for their broad-spectrum effects against parasites causing cytotoxicity and damage to the cellular DNA. In this study, we examined the toxicological changes of ivermectin (IVM) and doramectin (DME) with or without the co-administration of vitamin E (Vit. E) and selenium (Se). The drugs used were for animal use. Twenty-five adult male rats were divided into five groups. Group 1 (control) was given saline, Group 2 was given IVM (0.2 mg/kg b.w.), Group 3 was given IVM and Vit. E/Se (80/1.6 mg/kg b.w., respectively), Group 4 received DME (0.2 mg/kg b.w.), and Group 5 received DME and Vitamin E/Se. Both IVM and DME were given by subcutaneous injections whereas Vit. E and Se were given orally. All the treatments were given once per week throughout the eight weeks. Although the doses were off-label use, they were given in a long-term course to unveil their toxicity effects in a clear manner and the response of the amelioration. By 24-h after the 8<sup>th</sup> week, the rats were sacrificed. Their blood was sampled for the haematological and serobiochemical examinations. Histopathological changes and caspase-3 were determined in the hepatic and renal tissues. The histopathological findings showed that Vit. E and Se reduced the cellular changes induced by IVM or DME, indicating that Vit. E and Se protect against both types of avermectins, and that DME was safer than IVM. The cytotoxicity was assessed on a human embryo kidney (HEK) and skin cells by the SRB/IC<sub>50</sub> method and AO/EB (acridine orange-ethidium bromide) staining. Both IVM and DME caused apoptosis in the cultured HEK more than in the skin cells (80% vs. 30%, respectively). The cellular apoptosis in response to the IVM was more than that of DME, and the use of Vit. E and Se reduced the cytotoxicity as observed by caspase-3, in vivo, and IC<sub>50</sub>, in vitro.