Acute ivermectin toxicity on skin and brain tissue of adult albino rats: Evaluation of the role of Flumazenil and Vitamin C as new treatment modalities.

Ivermectin, a natural antiviral drug, has been recommended for treating various diseases, including Coronavirus Disease 2019. This study aimed to evaluate the potential histopathological and biochemical changes in the skin and brain of adult albino rats treated with ivermectin, as well as the effectiveness of Vitamin C and flumazenil in their treatment. Thirty rats were divided into five treatment groups, each containing six rats. After a week of acclimatization, different doses of ivermectin, Vitamin C, and flumazenil were administered to the rats. The rats were then euthanized. Histological and micro ribonucleic acid (miRNA) analysis of the skin and brain tissues, immunohistochemistry, and plasma collection from tail vein puncture were conducted to measure dopamine and interleukin 5 levels. The control group showed minimal acute toxicity, with an increase in hsa-miR535a-5p, dopamine, interleukin 5 (IL-5), and p-glycoprotein levels. In conclusion, the acute toxic effects of ivermectin in rats led to significant histological and morphological changes in both brain and skin tissues, along with oxidative stress and disruptions in P-glycoprotein, inflammatory cytokines, and the inflammatory response. Flumazenil and vitamin C may help normalize neuronal signaling, alleviate oxidative stress, and enhance dopamine release.