Repeated dose 28-day oral toxicity of ivermectin, azithromycin and acetaminophen in CD1 mouse

Abstract

The Covid-19 health crisis in Guatemala triggered self-medication with over-the-counter drugs among population. The World Health Organization suggests clinical trials to establish the risks of drugs used during the pandemic. The purpose of the current study is to evaluate the health toxic effects of three combined over-the-counter drugs (ivermectin, azithromycin and acetaminophen) on a standardized animal model (Mus musculus CD1 mice). An oral repeated dose toxicity assessment was performed in for 28 days, in 21 mice divided into three groups: control, dose and overdose. Hematological, biochemical, and histopathological values were estimated to assess the health status of the experimental groups. Significant changes were found in weight (p < .001), hematocrit (p < .001), hemoglobin concentration (p < .001), white blood cell count (p < .001), lymphocytes count (p < .05), red blood cell count (p < .001), blood urea nitrogen (p < .05), urea (p < .05), and total protein (p = 0.06). The consistent macroscopic lesions were friable liver (n = 2) and pale edges of the liver (n = 4); with also microscopic lesions of hydropic degeneration in the liver (n = 11), epithelial desquamation of intestinal cells (n = 8), hyalinization in the kidney (n = 7) and cloudy swelling in the liver (n = 5). Repeated overdoses of ivermectin, azithromycin, and acetaminophen decreased the health of experimental subjects. The health implications of repeated self-medication with these drugs are discussed