Department of Cardiology, Peking University First Hospital, Beijing, China.
Department of Ultrasound, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Biomed Res Int. 2020 May 8;2020:2616024. doi: 10.1155/2020/2616024. eCollection 2020.
Oxidative damage is closely involved in the development of doxorubicin- (DOX-) induced cardiotoxicity. It has been reported that tetrandrine can prevent the development of cardiac hypertrophy by suppressing reactive oxygen species- (ROS-) dependent signaling pathways in mice. However, whether tetrandrine could attenuate DOX-related cardiotoxicity remains unclear. To explore the protective effect of tetrandrine, mice were orally given a dose of tetrandrine (50 mg/kg) for 4 days beginning one day before DOX injection. To induce acute cardiac injury, the mice were exposed to a single intraperitoneal injection of DOX (15 mg/kg). The data in our study showed that tetrandrine prevented DOX-related whole-body wasting and heart atrophy, decreased markers of cardiac injury, and improved cardiac function in mice. Moreover, tetrandrine supplementation protected the mice against oxidative damage and myocardial apoptotic death. Tetrandrine supplementation also reduced ROS production and improved cell viability after DOX exposure in vitro. We also found that tetrandrine supplementation increased nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression and activity in vivo and in vitro. The protection of tetrandrine supplementation was blocked by Nrf2 deficiency in mice. In conclusion, our study found that tetrandrine could improve cardiac function and prevent the development of DOX-related cardiac injury through activation of Nrf2.
氧化损伤与多柔比星（DOX）诱导的心脏毒性的发展密切相关。据报道，粉防己碱可以通过抑制 ROS 依赖的信号通路来预防小鼠心肌肥厚的发生。然而，粉防己碱是否能减轻 DOX 相关的心脏毒性尚不清楚。为了探讨粉防己碱的保护作用，小鼠在 DOX 注射前一天开始每天口服给予粉防己碱（50mg/kg），连续 4 天。为了诱导急性心脏损伤，将小鼠单次腹腔注射 DOX（15mg/kg）。我们的研究数据表明，粉防己碱可预防 DOX 引起的全身消瘦和心脏萎缩，降低心脏损伤标志物，并改善小鼠的心脏功能。此外，粉防己碱补充可保护小鼠免受氧化损伤和心肌细胞凋亡。粉防己碱补充还可减少 DOX 暴露后体外的 ROS 产生和细胞活力下降。我们还发现，粉防己碱补充可增加体内和体外 Nrf2 的表达和活性。在小鼠中，Nrf2 缺陷可阻断粉防己碱补充的保护作用。总之，我们的研究发现，粉防己碱通过激活 Nrf2 可改善心脏功能并预防 DOX 相关的心脏损伤。
