Yang Hai-Bing, Lu Zhao-Yang, Yuan Wei, Li Wei-Dong, Mao Shang
Department of Cardiology, Yingshang First Hospital, Yingli Road, Fuyang, 236000, China.
Department of Cardiology, The Second Hospital of Shanxi Medical University, 382 Wuyi Road, Taiyuan, 030001, China.
Biol Trace Elem Res. 2022 Jun;200(6):2848-2856. doi: 10.1007/s12011-021-02891-z. Epub 2021 Aug 30.
Selenium (Se), an essential nutrient for humans, has been reported to possess cardioprotective effect. However, the protective effects of Se against doxorubicin (DOX)-induced cardiotoxicity and the underlying mechanism are rarely reported. In this study, we sought to explore whether Se protected against DOX-induced cardiotoxicity by inhibiting Nrf2-NLRP3 pathway. We found that Se treatment effectively alleviated DOX-induced myocardial dysfunctions, decreasing plasma markers associated with myocardial injury. Moreover, Se treatment significantly inhibited DOX-induced oxidative damages and pro-inflammatory cytokine expression in heart tissues. Furthermore, Se treatment markedly promoted the expression of Nrf2 and prevented the activation of NLRP3 inflammasome. Importantly, suppression of Nrf2 abolished the cardioprotective effects of Se and diminished the inhibition of Se on NLRP3 inflammasome. Collectively, our study demonstrated that Se might protect against DOX-induced cardiotoxicity via regulating Nrf2-NLRP3 pathway. Se supplementation may be a potential therapeutic strategy to protect against DOX-induced cardiac injury.
硒（Se）是人体必需的营养素，据报道具有心脏保护作用。然而，关于硒对阿霉素（DOX）诱导的心脏毒性的保护作用及其潜在机制的报道很少。在本研究中，我们试图探讨硒是否通过抑制Nrf2-NLRP3途径来预防DOX诱导的心脏毒性。我们发现，硒处理有效地减轻了DOX诱导的心肌功能障碍，降低了与心肌损伤相关的血浆标志物。此外，硒处理显著抑制了DOX诱导的心脏组织氧化损伤和促炎细胞因子表达。此外，硒处理显著促进了Nrf2的表达，并阻止了NLRP3炎性小体的激活。重要的是，抑制Nrf2消除了硒的心脏保护作用，并减弱了硒对NLRP3炎性小体的抑制作用。总的来说，我们的研究表明，硒可能通过调节Nrf2-NLRP3途径来预防DOX诱导的心脏毒性。补充硒可能是预防DOX诱导的心脏损伤的一种潜在治疗策略。
