Sulindac attenuates isoproterenol-induced myocardial injury: In vivo and molecular docking evidence

Objectives: Myocardial infarction (MI) arises when blood flow to a particular region of the heart is obstructed, leading to myocardial injury and characteristic electrocardiographic (ECG) abnormalities. Dysregulation of the Wnt/β-catenin signalling pathway has been implicated in post-MI cardiac remodelling. This study aimed to evaluate the cardioprotective potential of sulindac, a β-catenin inhibitor, in an isoproterenol (ISO)-induced rat model of MI. Materials and Methods: Myocardial infarction was induced in Wistar rats by subcutaneous administration of ISO. Sulindac was administered orally at doses of 2, 4, and 10 mg/kg. ECG changes, blood pressure, heart rate, oxidative stress markers, cardiac biomarkers, histopathological alterations, and β-catenin levels were evaluated. Molecular docking was performed to investigate the interaction of sulindac with tumour necrosis factor-alpha (7JRA), β-catenin (1A9U), and human interleukin-6 (1ALU) using a validated docking protocol. Results: Sulindac treatment significantly reduced heart rate, cardiac biomarkers, oxidative stress, and β-catenin levels while improving blood pressure and antioxidant enzyme activity in a dose-dependent manner. Histopathological examination demonstrated reduced inflammatory cell infiltration and myocardial fibrosis in sulindac-treated animals. Molecular docking revealed favourable interactions of sulindac with TNF-α, β-catenin, and human interleukin-6, supporting its potential multi-target activity. Conclusion: Sulindac attenuated ISO-induced myocardial injury and was associated with reduced β-catenin levels and favourable molecular docking interactions with inflammatory mediators and β-catenin. These findings suggest that sulindac may exert cardioprotective effects, potentially through modulation of the Wnt/β-catenin signalling pathway. However, further molecular studies are required to confirm the underlying mechanism and support its therapeutic potential in myocardial infarction.