Korea Food Research Institute, Wanju 55365, Republic of Korea.
Molecules. 2023 Dec 14;28(24):8090. doi: 10.3390/molecules28248090.
Doxorubicin (DOX), an anthracycline-based chemotherapeutic agent, is widely used to treat various types of cancer; however, prolonged treatment induces cardiomyotoxicity. Although studies have been performed to overcome DOX-induced cardiotoxicity (DICT), no effective method is currently available. This study investigated the effects and potential mechanisms of aqueous extract (PTA) in DICT. Changes in cell survival were assessed in H9c2 rat cardiomyocytes and MDA-MB-231 human breast cancer cells. The C57BL/6 mice were treated with DOX to induce DICT in vivo, and alterations in electrophysiological characteristics, serum biomarkers, and histological features were examined. The PTA treatment inhibited DOX-induced decrease in H9c2 cell viability but did not affect the MDA-MB-231 cell viability. Additionally, the PTA restored the abnormal heart rate, R-R interval, QT interval, and ST segment and inhibited the decrease in serum cardiac and hepatic toxicity indicators in the DICT model. Moreover, the PTA administration protected against myocardial fibrosis and apoptosis in the heart tissue of mice with DICT. PTA treatment restored DOX-induced decrease in the expression of NAD(P)H dehydrogenase quinone acceptor oxidoreductase 1 in a PTA concentration-dependent manner. In conclusion, the PTA inhibitory effect on DICT is attributable to its antioxidant properties, suggesting the potential of PTA as a phytotherapeutic agent for DICT.
多柔比星（DOX）是一种蒽环类化疗药物，广泛用于治疗各种类型的癌症；然而，长期治疗会导致心脏毒性。尽管已经进行了研究以克服多柔比星诱导的心脏毒性（DICT），但目前尚无有效的方法。本研究探讨了水提物（PTA）在 DICT 中的作用和潜在机制。在 H9c2 大鼠心肌细胞和 MDA-MB-231 人乳腺癌细胞中评估细胞存活率的变化。用 DOX 处理 C57BL/6 小鼠在体内诱导 DICT，并检查电生理特征、血清生物标志物和组织学特征的变化。PTA 处理抑制了 DOX 诱导的 H9c2 细胞活力下降，但不影响 MDA-MB-231 细胞活力。此外，PTA 恢复了 DICT 模型中异常的心率、R-R 间隔、QT 间隔和 ST 段，并抑制了血清心脏和肝脏毒性标志物的下降。此外，PTA 给药可防止 DICT 小鼠心脏组织中的心肌纤维化和细胞凋亡。PTA 处理以 PTA 浓度依赖的方式恢复了 DOX 诱导的 NAD(P)H 脱氢酶醌接受体氧化还原酶 1 表达的降低。总之，PTA 对 DICT 的抑制作用归因于其抗氧化特性，表明 PTA 作为 DICT 植物治疗剂的潜力。
