The Possible Effect of Ivermectin on the Liver of Adult Male Albino Rats

Abstract Background Ivermectin is a Food and Drug Administration (FDA) approved broad-spectrum anti- parasitic agent but not FDA-approved as an antiviral drug. It was shown to have anti-viral activity against a broad range of viruses and its consumption increased significantly during the Coronavirus disease 2019 (COVID-19), the worst pandemic in the past 100 years. So, further studies are required to detect the possible effect on the liver according to the admitted dose of ivermectin when used as an antiviral. Aim of the Work The aim of the current work was to study the structural changes in the liver and the biochemical changes in the liver function parameters of adult male albino rats after exposure to ivermectin in two different doses. Material and Methods 18 adult male albino rats weighing 200 – 250 grams were used in this study. The rats were randomized into 3 groups; Group I was composed of 6 rats and served as the control group without any treatment. Group II (low dose ivermectin treated) was composed of 6 rats and received (0.4 mg/kg body weight) 4 times daily. Group III (high dose ivermectin treated) was composed of 6 rats and received (4 mg/kg body weight) 4 times daily orally via oral gavage for 28 days dissolved in distilled water. At the end of the experiment, blood samples were collected for serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and Albumin. All the animals were sacrificed, and the liver was extracted and processed into paraffin blocks for light microscopic examination and were used for staining with hematoxylin and eosin (H&E), Masson Trichrome, and caspase-3 immunohistochemical reaction. A morphometric study and a statistical analysis were conducted. Results The general cellular morphology of the hepatocytes after ivermectin administration was greatly affected. This ranged from cellular swelling with hydropic degeneration and granular cytoplasm up to necrosis of hepatocytes. Other hepatocytes had indistinct cell boundaries and rarefied nuclei. Regarding the portal tract and blood sinusoids, they showed congestion and mononuclear cellular infiltration. Collagen deposition also showed an increase in its deposition around portal tracts and central veins. Caspase-3 showed a positive reaction. All these findings were more obvious in (Group III). Morphometric studies revealed a highly statistically significant increase in the area percentage of collagen fibers deposition and in the area percentage of caspase-3 expression. However, significant deterioration was observed in the level of ALT, AST, and ALP with no statistically significant increase in albumin levels. Conclusion Ivermectin oral intake as an antiviral evoked histopathological changes in the tissue when used in low and high doses which are higher doses than those required in treatment when used as an antiparasitic drug.