Protective effect of vitamin C against ivermectin induced nephrotoxicity in different age groups of male wistar rats: bio-histopathological study.

Abstract

Ivermectin (Ive) has exceedingly efficient against several microorganisms including viruses; therefore, it could help as a potential treatment of COVID-19. Because of increasing consumption of ivermectin and vitamin C (Vit.C) in hope to treat COVID-19, and because of ivermectin nephrotoxic effects have not been fully clarified especially in juvenile age, it was conducted to examine the histopathological and biochemical effects of ivermectin on adult and juvenile kidneys, and to assess the possible protective role of Vit.C against this potential toxicity. Rats were divided to 4 subgroups (Control subgroup, Vit.C subgroup, Ive subgroup, and Vit.C+Ive subgroup), 1 week after 4 doses of ivermectin (0.4 mg/kg Ive±1.25 mg/kg Vit.C), blood samples obtained for assessment of kidney function test, part of kidneys prepared for determination of matrix metalloproteinase-9 and antioxidant enzymes essay. Other parts prepared for histopathological and ultrastructural examination. Results showed that administration of ivermectin led to attenuation in kidney function and in activities of the antioxidant enzymes and increase in matrix metalloproteinase-9 activity. In addition, there were histological damages (shrunken glomeruli, widened urinary space, cytoplasmic vacuolation and pyknotic nuclei with epithelial exfoliation, extravasated blood, and mononuclear cell infiltration) and immunohistochemistry revealed increase in percentage of Bax proapoptotic protein expression. Also, ultrastructure examination showed alteration in cell architecture. All these changes were more obvious in juvenile group while co-administration of Vit.C led to significant protection more in adult group. In conclusion, Ivermectin should be used cautiously especially in juvenile age, and co-administration of Vit.C is highly recommended.