Morin mitigates doxorubicin-induced cardiotoxicity via suppression of oxidative stress, inflammation, and structural remodeling

The clinical use of the anticancer drug doxorubicin is restricted by its ability to cause cardiotoxicity, often progressing to heart failure. Current cardiovascular treatments fail to restore cardiac function or improve long-term survival rates, demanding alternative therapeutic approaches to minimize the cardiotoxicity of conventional cancer treatments. Thus, this study investigated the alleviating potential of morin, a flavonoid with known cardioprotective, antioxidant, and anti-inflammatory effects, against doxorubicin-induced cardiotoxicity at two different time points. Sixty male Wistar rats were used in this study, which was divided into concurrent and post-treatment phases, each including normal, morin, doxorubicin, and morin-treated doxorubicin groups. Cardiotoxicity was induced by six intraperitoneal injections of doxorubicin (2.5 mg/kg every 48 h), while morin (50 mg/kg) was administered orally either concurrent (post-initial doxorubicin injection) or post-treatment (after all doxorubicin injections) for 12 days. Assessment included echocardiography and Doppler imaging to assess cardiac function, as well as biochemical, histological, morphometric, and immuno-histochemical analyses. Administration of morin mitigated doxorubicin-induced cardiotoxicity by reversing structural damage, reducing fibrosis, and improving heart function. This was accompanied by increased total antioxidant capacity and reduced levels of malondialdehyde and creatine kinase-MB, as well as suppressed tumor necrosis factor-alpha, interleukin-6, and cleaved-caspase-3 expressions in cardiac tissue. In conclusion, morin demonstrates notable efficacy against doxorubicin-induced cardiotoxicity by mitigating oxidative stress, inflammation, and structural remodeling. Consequently, morin represents a viable pharmacological candidate that merits clinical exploration to avert heart failure progression during doxorubicin chemotherapy.