Cardio Protective Activity of Calophyllolide on Doxorubicin-induced Cardiac Toxicity

Background: Doxorubicin, a recognized anti-cancer medication, induces cardiotoxicity, thereby restricting its acceptability and application. The toxic effects stem from the generation of free radicals and damage to cardiomyocytes. Aim: This study examined the potential of Calophyllolide in mitigating doxorubicin-induced cardiotoxicity, given its noteworthy in vitro antioxidant properties. Methods: Rats in group I, serving as the normal control, were provided with a standard diet for 7 days. Animals in group II (DOX) were administered Doxorubicin (15 mg/kg body weight/day) subcutaneously, dissolved in physiological saline, on the 8th and 9th days, with a 24-hour interval, inducing myocardial infarction. In groups III and IV, animals received calophyllolide at doses of 200 mg/kg and 400 mg/kg, respectively, for 7 days before being injected with the aforementioned dose of DOX. Upon concluding the study, blood samples were collected via retroorbital puncture for serum, utilized in estimating lipid and liver profile tests such as ALT, AST, LDL, HDL, cholesterol, etc. Additionally, the hearts were isolated and homogenized with tris buffer, and the supernatant layer was used for assessing cardiac biomarkers. Results: Dox-treated animals showed abnormalities in ECG and also elevated the liver profile parameters, lipid parameters, and cardiac biomarkers. Whereas Calophyllolide 400 mg/kg treated animals restored the ECG waves to normal and also reduced the biomarkers. The potential cardioprotective benefits of Calophyllolide may be associated with its impact on the ST interval, mitigating myocardial pathological damage. Calophyllolide demonstrates protective effects on H9c2 cells against Doxorubicin-induced cardiac injury by enhancing cell viability, reducing LDH and ROS leakage, and lowering levels of troponin and inflammatory mediators. Conclusion: This study results endorse the positive contribution of Calophyllolide in safeguarding against ischemic cardiomyopathy. Major Findings: Calophyllolide demonstrates significant cardioprotective effects against DOX-induced toxicity by restoring cardiac function parameters such as R wave amplitude, ST interval, LVEDP, and LVSP. It effectively reduced markers of cardiac injury and inflammation, including Tn-I, CK-MB, LDH, TNF-α, and IL-6. Additionally, it improves the liver enzymes and lipid profiles by normalizing SGOT, SGPT, ALP, LDL, TC, and HDL levels. Histopathological analysis further confirms the cardioprotective efficiency of calophyllolide.