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.

中文翻译：

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硒通过 Nrf2-NLRP3 通路减弱阿霉素诱导的心脏毒性。

硒 (Se) 是人类必需的营养素，据报道具有心脏保护作用。然而，硒对阿霉素（DOX）诱导的心脏毒性的保护作用及其潜在机制却鲜有报道。在这项研究中，我们试图探索硒是否通过抑制 Nrf2-NLRP3 通路来保护免受 DOX 诱导的心脏毒性。我们发现硒治疗有效缓解了 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，硒处理显着抑制了 DOX 诱导的心脏组织中的氧化损伤和促炎细胞因子的表达。此外，硒处理显着促进了 Nrf2 的表达并阻止了 NLRP3 炎性体的激活。重要的，Nrf2 的抑制消除了 Se 的心脏保护作用并减少了 Se 对 NLRP3 炎性体的抑制。总的来说，我们的研究表明，硒可能通过调节 Nrf2-NLRP3 通路来预防 DOX 诱导的心脏毒性。补充硒可能是一种潜在的治疗策略，可以防止 DOX 引起的心脏损伤。