Acute toxicity events of ivermectin in chicks’ model

Abstract

Ivermectin is a very safe drug; however, there are many studies on its toxic effects in different animals due to sensitivity, misuse, or accidental overdose. This study aimed to further characterize the neurotoxic effects of ivermectin in chicks and identify possible therapeutic strategies for use in cases of ivermectin toxicity. The LD₅₀ of ivermectin was determined by the Dixon method. The acute toxicity signs of ivermectin were induced at doses of 131.5,2629 and 394.5 mg/kg orally. The therapeutic effect of flumazenil on ivermectin poisoning was also studied. Administration of repeated doses of ivermectin for five consecutive days was recorded to measure the neurobehavioral within the open field and tonic immobility test. The oral LD₅₀ of ivermectin was 525.9mg/kg. The acute signs of poisoning on ivermectin-treated chicks were lethargy, ataxia, tremor, diarrhea, recumbency, and death. Flumazenil at a dose of 0.1mg/kg significantly reduced the toxicity signs induced by the ivermectin in chicks, especially tremor and ataxia, and prevented death. The administration of ivermectin at 26.3, 52.6, and 105.2 mg/kg doses led to a significant decrease in motor activity through a significant increase in the time of starting the movement and a decrease in the number of cross lines. We concluded that ivermectin has a neurotoxic effect in chicks when used in high doses; the results also indicate a potential clinical application of flumazenil for treatment side effects and toxicity of ivermectin, as well as ivermectin, has depressant effect in chicks represented by open-field activity.