α-Arbutin Attenuates Doxorubicin-induced Cardiotoxicity via Modulation of Oxidative Stress and Autonomic Function in Rats

Introduction: Doxorubicin (Dox) has limited clinical usefulness because of its cardiotoxicity, which puts patients at significant risk. To reduce adverse cardiac effects while simultaneously inhibiting tumor growth, effective cardioprotective strategies are essential. Our study demonstrates that vagus nerve stimulation reduces myocyte apoptosis, mitochondrial dysfunction, and improves cardiac function, and that a balanced autonomic tone can be produced by α-Arbutin pretreatment. Methods: To induce experimental cardiomyopathy, rats were continuously treated with Dox (15 mg/kg; intraperitoneal). α-Arbutin was administered as pretreatment for 21 days at two dosages (25 mg/kg and 50 mg/kg; orally) to assess its effects on the heart and on biochemical indicators of oxidative stress, enzymatic activity, hemodynamics, and cardiac tissue damage. Results: The study indicated that Doxorubicin administration led to significant cardiac injury, demonstrated by a reduction in the heart-weight-to-body-weight ratio and increased activity of marker enzymes such as CK-MB, AST, LDH, and calcium. Decreases in systolic, diastolic, and mean blood pressure, heart rate, ECG parameters, and autonomic regulation of the brain-heart axis (HRV) were observed and evaluated against the subsequent outcomes in the treatment group. Discussion: α-Arbutin's antioxidant activity helped counter Doxorubicin-induced oxidative stress and autonomic imbalance, supporting existing studies on natural cardioprotective agents. Its efficacy at 50 mg/kg across biochemical, ECG, HRV, and tissue levels is notable. However, the study lacks molecular insights and long-term evaluation. Future research should explore signaling mechanisms and clinical relevance. Conclusion: α-Arbutin demonstrated cardioprotective effects by reducing oxidative stress and stabilizing cardiac function, particularly at 50 mg/kg. It holds potential as a supportive agent against Doxorubicin-induced cardiomyopathy.