Shaernejad Sina, Nosrat Ali, Baeeri Maryam, Hashemi Goradel Nasser, SeyedSadeghi Mirsalim, Akbariani Mostafa, Arabzadeh AmirAhmad, Rahimifard Mahban, Haghi-Aminjan Hamed
Students Research Committee, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.
Toxicology and Diseases Specialty Group, Pharmaceutical Sciences Research Center (PSRC), Tehran University of Medical Sciences (TUMS), Tehran, Iran.
Cancer Cell Int. 2025 May 22;25(1):186. doi: 10.1186/s12935-025-03828-5.
Despite the undeniable role of chemotherapeutics in cancer treatment, their administration may be associated with various side effects. Cardiac injury is among the most crucial side effects related to the induction of chemotherapeutic agents. Since the heart is a vital organ, cardiotoxicity often prevents clinicians from continuing chemotherapy. Hesperidin and hesperetin, flavonoids derived from citrus fruits, possess several pharmaceutical properties. This study firstly explores the cardioprotective effects of hesperidin and hesperetin against chemotherapy-induced cardiotoxicity mechanisms, emphasizing their potential as adjunctive therapies. Key literature gaps are identified, and further mechanistic studies will be proposed. The findings underscore the translational potential of these flavonoids, advocating for rigorous preclinical optimization and clinical trials to validate their efficacy and safety. This review lays a foundation for integrating natural compounds into cardioprotective strategies in oncology. A systematic search was conducted in databases (PubMed, Scopus, ISI) until May 2025, according to PRISMA principles. The search terms were chosen according to our research objective and queried in the title and abstract. Following the screening of 82 papers, twelve articles were selected based on our inclusion and exclusion criteria. Based on the evaluated results, chemotherapy adversely affects cardiac tissue, leading to elevated risks of morbidity and mortality. Co-administration of hesperidin and hesperetin with chemotherapy prevents heart injury and preserves cardiac function, maintaining it almost like a normal heart. The protective role of hesperidin and hesperetin is based on their ability to fight free radicals, reduce inflammation, and stop cell death. Nonclinical investigations indicate that hesperidin and hesperetin ameliorate chemotherapy-induced cardiotoxicity. Nonetheless, they may influence the efficacy of anticancer medications, which primarily function by elevating oxidants, inflammation, and apoptosis. This indicates that meticulously designed trials are necessary to evaluate the efficacy and safety of this combination along with the synergistic potential of them in preventing chemotherapy-induced cardiotoxicity while maintaining anticancer effectiveness.
尽管化疗药物在癌症治疗中具有不可否认的作用，但其使用可能会伴随各种副作用。心脏损伤是与化疗药物诱导相关的最关键副作用之一。由于心脏是重要器官，心脏毒性常常使临床医生无法继续进行化疗。橙皮苷和橙皮素是源自柑橘类水果的黄酮类化合物，具有多种药理特性。本研究首先探讨橙皮苷和橙皮素对化疗诱导的心脏毒性机制的心脏保护作用，强调它们作为辅助治疗的潜力。确定了关键的文献空白，并将提出进一步的机制研究。研究结果强调了这些黄酮类化合物的转化潜力，主张进行严格的临床前优化和临床试验以验证其疗效和安全性。本综述为将天然化合物整合到肿瘤学心脏保护策略中奠定了基础。根据PRISMA原则，在截至2025年5月的数据库（PubMed、Scopus、ISI）中进行了系统检索。根据我们的研究目标选择检索词，并在标题和摘要中进行查询。在筛选了82篇论文后，根据我们的纳入和排除标准选择了12篇文章。根据评估结果，化疗对心脏组织有不良影响，导致发病和死亡风险升高。橙皮苷和橙皮素与化疗联合使用可预防心脏损伤并保留心脏功能，使其几乎保持正常心脏状态。橙皮苷和橙皮素的保护作用基于它们对抗自由基、减轻炎症和阻止细胞死亡的能力。非临床研究表明，橙皮苷和橙皮素可改善化疗诱导的心脏毒性。尽管如此，它们可能会影响抗癌药物的疗效，抗癌药物主要通过升高氧化剂、炎症和细胞凋亡起作用。这表明需要精心设计试验来评估这种组合的疗效和安全性，以及它们在预防化疗诱导的心脏毒性同时保持抗癌效果方面的协同潜力。
