Protective effects of vitamin E and grape seed oil against acute hepatorenal ivermectin toxicity in mice: biochemical and histopathological studies

Abstract

Ivermectin (IVM), a broad spectrum anthelmintic drug, is considered a safe drug; however, there are few reports about its toxic effects in particularly at accidental overdose exposure. Therefore, the current study was designed to investigate the potential protective roles of vitamin E (Vit E) and grape seed oil (GSO) against the acute hepatorenal toxicity of IVM in mice. Mice were divided into four equal groups. Control vehicle group was administrated corn oil (0.2 ml/animal), IVM group was administrated IVM (6.5 mg/kg b.w.), Vit E+IVM group was administrated Vit E (200 mg/kg b.w.) plus IVM and GSO+IVM group was administrated GSO (0.2 ml/animal) plus IVM. All treatments were orally administrated daily for 3 weeks while IVM is administered as a single oral dose one day before the end of the experiment. The results revealed that IVM induced significant elevation in serum ALT and AST activities; urea and creatinine levels without any significant change in glucose level. No marked histopathological alterations were observed in hepatic tissue with several pathological alterations in the kidneys of IVM-intoxicated mice. However, pretreatment of mice with either Vit E or GSO ameliorated the IVM-induced biochemical and histopathological alterations. In conclusion, Vit E and GSO may provide a similar promising protective value against IVM acute hepatorenal intoxication.

Assessment of Avermectins-Induced Toxicity in Animals

“…The evaluation of serum creatinine and the blood urea levels post-administration of drugs provides a good overview for nephrotoxicity analysis [ 46 ]. Various studies conducted on avermectins (mainly the ivermectin and the abamectin) have proven these drugs to induce nephrotoxicity in many animals like mice, bats, rabbits, and rats [ 28 , 34 , 53 , 54 , 55 , 56 ]. The main molecular mechanism through which avermectins exert their nephrotoxic effect is the lipid peroxidation which results from the action of reactive oxygen species [ 51 ].…”

“…Various studies have also indicated the avermectins to have toxic effects on animals [ 26 , 27 , 28 , 29 ]. For example, collie dogs experiencing severe illness presented to the clinic were found to be suffering from ivermectin toxicity [ 30 ].…”