Department of Cardiology, Huanggang Central Hospital, Huanggang, China.
Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Cardiovasc Toxicol. 2024 Aug;24(8):818-835. doi: 10.1007/s12012-024-09882-1. Epub 2024 Jun 19.
Doxorubicin (DOX) is an effective anticancer agent, yet its clinical utility is hampered by dose-dependent cardiotoxicity. This study explores the cardioprotective potential of Marein (Mar) against DOX-induced cardiac injury and elucidates underlying molecular mechanisms. Neonatal rat cardiomyocytes (NRCMs) and murine models were employed to assess the impact of Mar on DOX-induced cardiotoxicity (DIC). In vitro, cell viability, oxidative stress were evaluated. In vivo, a chronic injection method was employed to induce a DIC mouse model, followed by eight weeks of Mar treatment. Cardiac function, histopathology, and markers of cardiotoxicity were assessed. In vitro, Mar treatment demonstrated significant cardioprotective effects in vivo, as evidenced by improved cardiac function and reduced indicators of cardiac damage. Mechanistically, Mar reduced inflammation, oxidative stress, and apoptosis in cardiomyocytes, potentially via activation of the Focal Adhesion Kinase (FAK)/AKT pathway. Mar also exhibited an anti-ferroptosis effect. Interestingly, Mar did not compromise DOX's efficacy in cancer cells, suggesting a dual benefit in onco-cardiology. Molecular docking studies suggested a potential interaction between Mar and FAK. This study demonstrates Mar's potential as a mitigator of DOX-induced cardiotoxicity, offering a translational perspective on its clinical application. By activating the FAK/AKT pathway, Mar exerts protective effects against DOX-induced cardiomyocyte damage, highlighting its promise in onco-cardiology. Further research is warranted to validate these findings and advance Mar as a potential adjunctive therapy in cancer treatment.
阿霉素（DOX）是一种有效的抗癌药物，但由于剂量依赖性的心脏毒性，其临床应用受到限制。本研究探讨了马里因（Mar）对 DOX 诱导的心脏损伤的心脏保护潜力，并阐明了潜在的分子机制。采用新生大鼠心肌细胞（NRCM）和小鼠模型来评估 Mar 对 DOX 诱导的心脏毒性（DIC）的影响。在体外，评估细胞活力和氧化应激。在体内，采用慢性注射方法诱导 DIC 小鼠模型，然后进行八周的 Mar 治疗。评估心脏功能、组织病理学和心脏毒性标志物。在体内，Mar 治疗显示出显著的心脏保护作用，表现为心脏功能改善和心脏损伤标志物减少。机制上，Mar 通过激活粘着斑激酶（FAK）/蛋白激酶 B（AKT）通路减少心肌细胞中的炎症、氧化应激和细胞凋亡。Mar 还表现出抗铁死亡作用。有趣的是，Mar 并没有损害 DOX 在癌细胞中的疗效，这表明其在肿瘤心脏病学中有双重获益。分子对接研究表明 Mar 与 FAK 之间可能存在相互作用。本研究表明 Mar 有潜力作为 DOX 诱导的心脏毒性的缓解剂，为其临床应用提供了转化视角。Mar 通过激活 FAK/AKT 通路对 DOX 诱导的心肌细胞损伤发挥保护作用，这突显了其在肿瘤心脏病学中的前景。需要进一步的研究来验证这些发现，并推进 Mar 作为癌症治疗中潜在的辅助治疗方法。
