Department of Pharmacology and Therapeutics, College of Medicine, Qassim University, Buraidah, 51452, Saudi Arabia; Department of Clinical Pharmacology, Faculty of Medicine, Mansoura University, Mansoura, 35516, Egypt.
Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, Egypt.
Eur J Pharm Sci. 2024 Sep 1;200:106849. doi: 10.1016/j.ejps.2024.106849. Epub 2024 Jul 9.
Doxorubicin (DOX) is an anthracycline chemotherapy drug widely employed in the treatment of various cancers, known for its potent antineoplastic properties but often associated with dose-dependent cardiotoxicity, limiting its clinical use. This review explores the complex molecular details that determine the heart-protective effectiveness of carvedilol in relation to cardiotoxicity caused by DOX. The harmful effects of DOX on heart cells could include oxidative stress, DNA damage, iron imbalance, disruption of autophagy, calcium imbalance, apoptosis, dysregulation of topoisomerase 2-beta, arrhythmogenicity, and inflammatory responses. This review carefully reveals how carvedilol serves as a strong protective mechanism, strategically reducing each aspect of cardiac damage caused by DOX. Carvedilol's antioxidant capabilities involve neutralizing free radicals and adjusting crucial antioxidant enzymes. It skillfully manages iron balance, controls autophagy, and restores the calcium balance essential for cellular stability. Moreover, the anti-apoptotic effects of carvedilol are outlined through the adjustment of Bcl-2 family proteins and activation of the Akt signaling pathway. The medication also controls topoisomerase 2-beta and reduces the renin-angiotensin-aldosterone system, together offering a thorough defense against cardiotoxicity induced by DOX. These findings not only provide detailed understanding into the molecular mechanisms that coordinate heart protection by carvedilol but also offer considerable potential for the creation of targeted treatment strategies intended to relieve cardiotoxicity caused by chemotherapy.
多柔比星（DOX）是一种广泛用于治疗各种癌症的蒽环类化疗药物，以其强大的抗肿瘤特性而闻名，但常伴有剂量依赖性心脏毒性，限制了其临床应用。本综述探讨了决定卡维地洛在多柔比星引起的心脏毒性方面的心脏保护效果的复杂分子细节。多柔比星对心脏细胞的有害影响可能包括氧化应激、DNA 损伤、铁失衡、自噬中断、钙失衡、细胞凋亡、拓扑异构酶 2-β 的调节失常、心律失常和炎症反应。本综述仔细揭示了卡维地洛如何作为一种强大的保护机制，战略性地减轻 DOX 引起的心脏损伤的各个方面。卡维地洛的抗氧化能力包括中和自由基和调整关键的抗氧化酶。它巧妙地管理铁平衡、控制自噬并恢复细胞稳定性所必需的钙平衡。此外，卡维地洛的抗细胞凋亡作用通过调节 Bcl-2 家族蛋白和激活 Akt 信号通路来描述。该药物还控制拓扑异构酶 2-β 并降低肾素-血管紧张素-醛固酮系统，共同为多柔比星引起的心脏毒性提供全面保护。这些发现不仅提供了协调卡维地洛心脏保护作用的分子机制的详细理解，还为创建旨在减轻化疗引起的心脏毒性的靶向治疗策略提供了巨大潜力。
