The role of hesperidin as a cardioprotective strategy against doxorubicin-induced cardiotoxicity: The antioxidant, anti-inflammatory, antiapoptotic, and cytoprotective potentials.

Background: Doxorubicin (DOX), an anthracycline antibiotic, is a powerful chemotherapeutic agent effective against multiple types of cancer, particularly lung, breast, bladder and hematologic neoplasia (lymphomas and leukemia). However, its therapeutic usage is restricted by its known cardiotoxicity, which is associated with the production of oxidative stress. Enhancing antioxidant capacity represents a promising approach to mitigate DOX-induced cardiotoxicity. Hesperidin (HES), a citrus bioflavonoid, possesses several pharmacological effects, such as anti-inflammatory and antioxidant characteristics. Aim: This study was designed to evaluate the cardiotoxicity of DOX and assess the possible cardioprotective role of HES. Methods: Groups of Wistar rats were either treated with DOX (4 mg/kg. bw., once a week for five consecutive weeks, intraperitoneally) or received co-treatment with HES (100 mg/kg. bw./day in distilled water, 5 days in a week for five consecutive weeks, administered orally). Heart and blood samples were obtained for histological, immunohistochemical, and biochemical assessments. Results: DOX administration resulted in severe cardiotoxicity, as evidenced by significant elevations in cardiac biomarkers, including Troponin I (CTnI), Creatine kinase (CK-Total), Creatine kinase isoenzyme-MB (CK-MB), lactate dehydrogenase (LDH), and Aspartate aminotransferase (AST). DOX also elevated pro-inflammatory cytokines, such as Interferon Conclusion: We can conclude that DOX induces severe cardiotoxicity characterized by oxidative stress, inflammation, pathological alterations, and apoptosis. Co-treatment with HES demonstrates significant cardioprotective effects by virtue of its potent anti-inflammatory, antioxidant, cytoprotective, and antiapoptotic characteristics.