The neurological, cardiac, and hepatic toxic effects of ivermectin and hydroxychloroquine and the ameliorative role of vitamin C: a biochemical, histological, and immunohistochemical experimental study

Abstract Background Physicians ought to be cautious about the toxic impact of an extensive range of potentially unproven medications when evaluating or managing disease outbreaks. This work aimed to evaluate the potentially toxic effects of ivermectin and hydroxychloroquine, which were used in the pandemic COVID 19; and in other various diseases, and then to assess the potentially protective effects of vitamin C in alleviating the toxic effects of these two drugs. Sixty Wistar albino rats were grouped into six groups (control, vitamin C-treated, ivermectin-treated, hydroxychloroquine-treated, ivermectin + vitamin C-treated, and hydroxychloroquine + vitamin C-treated groups). Serum biomarkers were measured, and the rats’ tissues were subjected to biochemical studies; oxidant and antioxidant biomarkers, histological and immunohistochemical examinations. Results Ivermectin and hydroxychloroquine significantly elevated serum biomarkers, MDA, and NO levels in examined organs and lowered GSH and SOD levels in brain and liver while elevated antioxidants levels in cardiac tissues. Additionally, they induced marked histopathological changes, increased collagen deposition, and increased expression of Cleaved Caspase-3 immune reactivity in neural, cardiac, and hepatic tissues. With the help of vitamin C, all alterations began to revert to their normal state. Conclusion It was confirmed that administering repeated doses of ivermectin or hydroxychloroquine could induce detrimental toxic impacts on the cerebral cortex, heart, and liver through various analytical mechanisms. The use of vitamin C had significant protective capacities against these toxic effects.