Cardioprotective Effects of Zonisamide and Dexrazoxane Against Doxorubicin-Induced Cardiotoxicity in Rats; Role of Inflammation and Oxidative Stress

Anthracyclines, including doxorubicin (DOX), represent some of the most effective therapies for numerous tumors; yet, their practical application is constrained by adverse effects, notably cardiotoxicity. The research aimed to explore the cardioprotective effect of zonisamide (ZON), dexrazoxane (DEX), and their combined regimen on doxorubicin-induced cardiac damage in a rat model. Thirty male adult Albino Wistar rats (200-250g) were assigned to five groups: Control group, DOX group, DEX-treated group, ZON-treated group, and combination group. On days 1, 6, and 11, DOX (5 mg/Kg) was injected intraperitoneally to induce cardiotoxicity. After two weeks, hematological parameters, cardiac injury markers, antioxidant markers, and proinflammatory cytokines were measured. The results showed that DOX significantly reduced red blood cells count (RBCs), hemoglobin (Hb), lymphocytes, monocytes, reduced glutathione (GSH), and nitric oxide (NO) level; however, it significantly increased aspartate aminotransferase (AST), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Pretreatment of DEX, ZON, and their combination for 2 weeks significantly decreased the aforementioned alterations induced by DOX. The study indicated that DEX and ZON could improve cardiotoxicity induced by DOX.