Protective effects of <i>Melissa officinalis</i> ethanolic extract on doxorubicin-induced cardiotoxicity in a rat model

Despite its proven efficacy in cancer treatment, doxorubicin's therapeutic potential is limited by cumulative, dose-dependent cardiotoxicity, primarily associated with oxidative stress. Given the well-documented antioxidant properties of Melissa officinalis L., this study aimed to assess the cardioprotective potential of its ethanolic extract (MOE) against doxorubicin-induced cardiotoxicity (DIC). Twenty-one female Wistar albino rats were randomly divided into three groups: CTRL (healthy, untreated), DOX (doxorubicin-treated), and DOX-MO (treated with both doxorubicin and MOE). Doxorubicin (15 mg/kg, i.p.) was administered on Day 7, while MOE (200 mg/kg, orally) was given daily for 10 days. Cardiac function was evaluated using echocardiography and Langendorff-perfused hearts, followed by analysis of oxidative stress markers and morphometric analysis. MOE improved cardiac function and partially preserved myocardial architecture following DIC, significantly reducing fibrosis compared to the DOX group. Nitrite levels were significantly elevated in MOE-treated rats, suggesting preserved endothelial function and enhanced nitric oxide-mediated vasodilation. These results suggest that MOE may mitigate DIC through antioxidative and vasodilatory mechanisms, as well as by preserving endothelial and myocardial integrity. Histological findings further indicate a possible reduction in inflammatory changes, supporting a modest anti-inflammatory effect. These findings suggest that MOE may have cardioprotective potential against DIC, warranting further investigation in preclinical and clinical settings.