The Influence of Melatonin in Doxorubicin-Induced Cardiotoxicity: In Vivo study

Doxorubicin (DOX) is one of the most effective chemotherapeutic agents; yet, its clinical application is limited due to dose dependent cardiotoxicity, which worsens by increasing cumulative dose and is largely associated with oxidative stress and damage to cardiomyocyte. Despite numerous studies, proper methods to protect the heart during DOX therapy remain a critical challenge. Melatonin (MLT), a naturally endogenous hormone with antioxidant and cardio-protection properties, identified as a possible treatment to reduce DOX-induced cardiac damage. This study aimed to evaluate the protective role of MLT against DOX-induced cardiotoxicity using experimental rat models. Thirty male albino rats were separated into three groups: control group, DOX-treated group (3mg/kg/week, intraperitoneally, for 6 weeks), and DOX+MLT co-administration group (MLT;30 mg /kg/day, orally). After 42 days, serum biomarkers of oxidative stress and cardiac injury, as well as histological examination of cardiomyocyte tissue, were assessed. The administration of DOX resulted in considerable cardiac stress, as demonstrated by a significant increase in serum brain natriuretic peptide (BNP) (p<0.0001) and elevated malondialdehyde (MDA) levels(p<0.05), indicating oxidative lipid damage. Co-treatment with MLT greatly reduced the BNP (p<0.0001), and MDA levels. Other serum markers, including cardiac troponin-I (cTnT-I), lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), nitric oxide (NO), showed non-significant changes. Collectively, the analysis revealed a significant structural advantage, MLT treatment markedly improved DOX-induced myocardial damage, significant reduction in cardiomyocyte hypertrophy, coronary artery wall thickening, and necrotic areas, thereby reducing the injury from moderate or severe to mild changes. These findings indicate that MLT exerts cardio-protection effects, likely through reducing oxidative stress and maintaining myocardial structure.