Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the NMPA and State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou 511436, China.
The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Guangzhou Medical University, Guangzhou, Qingyuan 511500, China.
Phytomedicine. 2024 Jul;129:155673. doi: 10.1016/j.phymed.2024.155673. Epub 2024 Apr 22.
Doxorubicin (DOX) is a widely utilized anthracycline chemotherapy drug in cancer treatment, yet its efficacy is hindered by both short-term and long-term cardiotoxicity. Although oxidative stress, inflammation and mitochondrial dysfunction are established factors in DOX-induced cardiotoxicity, the precise molecular pathways remain elusive. Further exploration of the pathogenesis and identification of novel molecular targets are imperative. Recent studies have implicated the Sirtuins family in various physiological and pathological processes, suggesting their potential in ameliorating DOX-induced cardiotoxicity. Moreover, research on Sirtuins has discovered small-molecule compounds or medicinal plants with regulatory effects, representing a notable advancement in preventing and treating DOX-induced cardiac injury.
In this review, we delve into the pathogenesis of DOX-induced cardiotoxicity and explore the therapeutic effects of Sirtuins in mitigating this condition, along with the associated molecular mechanisms. Furthermore, we delineate the roles and mechanisms of small-molecule regulators of Sirtuins in the prevention and treatment of DOX-induced cardiotoxicity.
STUDY-DESIGN/METHODS: Data for this review were sourced from various scientific databases (such as Web of Science, PubMed and Science Direct) up to March 2024. Search terms included "Sirtuins," "DOX-induced cardiotoxicity," "DOX," "Sirtuins regulators," "histone deacetylation," among others, as well as several combinations thereof.
Members of the Sirtuins family regulate both the onset and progression of DOX-induced cardiotoxicity through anti-inflammatory, antioxidative stress and anti-apoptotic mechanisms, as well as by maintaining mitochondrial stability. Moreover, natural plant-derived active compounds such as Resveratrol (RES), curcumin, berberine, along with synthetic small-molecule compounds like EX527, modulate the expression and activity of Sirtuins.
The therapeutic role of the Sirtuins family in mitigating DOX-induced cardiotoxicity represents a potential molecular target. However, further research is urgently needed to elucidate the relevant molecular mechanisms and to assess the safety and biological activity of Sirtuins regulators. This review offers an in-depth understanding of the therapeutic role of the Sirtuins family in mitigating DOX-induced cardiotoxicity, providing a preliminary basis for the clinical application of Sirtuins regulators in this condition.
多柔比星（DOX）是癌症治疗中广泛应用的蒽环类化疗药物，但由于短期和长期的心脏毒性，其疗效受到限制。尽管氧化应激、炎症和线粒体功能障碍是多柔比星诱导的心脏毒性的既定因素，但确切的分子途径仍不清楚。进一步探索发病机制和确定新的分子靶点至关重要。最近的研究表明，Sirtuins 家族参与了各种生理和病理过程，表明它们在改善多柔比星诱导的心脏毒性方面具有潜力。此外，Sirtuins 的研究发现了具有调节作用的小分子化合物或药用植物，这是预防和治疗多柔比星诱导的心脏损伤的一个显著进展。
在本综述中，我们深入探讨了多柔比星诱导的心脏毒性的发病机制，并探讨了 Sirtuins 在减轻这种情况方面的治疗效果，以及相关的分子机制。此外，我们还阐述了 Sirtuins 的小分子调节剂在预防和治疗多柔比星诱导的心脏毒性中的作用和机制。
研究设计/方法：本综述的数据来自于各种科学数据库（如 Web of Science、PubMed 和 Science Direct），检索时间截至 2024 年 3 月。检索词包括“Sirtuins”、“多柔比星诱导的心脏毒性”、“多柔比星”、“Sirtuins 调节剂”、“组蛋白去乙酰化”等，以及它们的多种组合。
Sirtuins 家族的成员通过抗炎、抗氧化应激和抗细胞凋亡机制，以及维持线粒体稳定性，调节多柔比星诱导的心脏毒性的发生和进展。此外，天然植物来源的活性化合物，如白藜芦醇（RES）、姜黄素、小檗碱，以及合成的小分子化合物，如 EX527，调节 Sirtuins 的表达和活性。
Sirtuins 家族在减轻多柔比星诱导的心脏毒性方面的治疗作用代表了一个潜在的分子靶点。然而，迫切需要进一步研究以阐明相关的分子机制，并评估 Sirtuins 调节剂的安全性和生物学活性。本综述深入了解了 Sirtuins 家族在减轻多柔比星诱导的心脏毒性方面的治疗作用，为 Sirtuins 调节剂在该疾病中的临床应用提供了初步基础。
