Zhao Changzhi, Xiao Congshu, Feng Songqiao, Bai Jianxin
Second Affiliated Hospital of Dalian Medical University, Dalian, China.
Dalian Municipal Friendship Hospital, Dalian, China.
Front Pharmacol. 2023 Apr 25;14:1177542. doi: 10.3389/fphar.2023.1177542. eCollection 2023.
The liver plays a critical role in sepsis, which is a serious worldwide public health problem. A novel mechanism of controlled cell death called ferroptosis has recently been described. Disrupted redox equilibrium, excessive iron, and enhanced lipid peroxidation are key features of ferroptosis. It is unknown how ferroptosis affects liver damage caused by sepsis. In the present study, we aimed to elucidate the pathways and explore the impact of artemisitene (ATT) on ferroptosis in sepsis-induced liver injury. Our findings demonstrated that ATT significantly decreased liver damage and ferroptotic characteristics. Additionally, ATT significantly reduced the expression of the nuclear factor-κB (NF-κB) subunit to reduce LPS-induced hepatic oxidative stress and inflammation and upregulated the expression of nuclear factor-erythroid 2 (NF-E2)-related factor 2 (Nrf2) and its downstream protein heme oxygenase 1 (HO-1). This may offer a new strategy for preventing LPS-induced hepatic injury.
肝脏在脓毒症中起着关键作用，脓毒症是一个严重的全球性公共卫生问题。最近描述了一种称为铁死亡的新型细胞程序性死亡机制。氧化还原平衡破坏、铁过量和脂质过氧化增强是铁死亡的关键特征。目前尚不清楚铁死亡如何影响脓毒症所致的肝损伤。在本研究中，我们旨在阐明其机制，并探讨青蒿烯（ATT）对脓毒症诱导的肝损伤中铁死亡的影响。我们的研究结果表明，ATT可显著减轻肝损伤和铁死亡特征。此外，ATT可显著降低核因子κB（NF-κB）亚基的表达，以减轻脂多糖（LPS）诱导的肝脏氧化应激和炎症，并上调核因子红细胞2（NF-E2）相关因子2（Nrf2）及其下游蛋白血红素加氧酶1（HO-1）的表达。这可能为预防LPS诱导的肝损伤提供一种新策略。
