Selenium has a double action. (i) Seleno-compounds, among them sodium selenite have a direct pro-oxidant action leading to acute toxicity but may be also beneficial as drug. (ii) Selenium is an essential anti-oxidant required for anti-oxidant seleno-enzymes. Septic shock is a common severe syndrome leading to endothelium damage and multiple organ failure, with increased data suggesting the principle role of oxidative stress. Selenoprotein P, main selenium constituent of the plasma, may decrease dramatically and specifically in septic shock patients and may be involved in the endothelium protection. A prospective, multi-center placebo-controlled, randomized, double-blind study in severe septic shock patients with documented infection has been preformed. Patients received, for 10 days, selenium as sodium selenite (4000 microg on the first day, 1000 microg/day on the 9 following days) or matching placebo using continuous intravenous infusion. Mortality rates did not significantly differ between groups at any time point. Adverse events rates were similar in the two groups. However, high-dose selenium administration has been associated with a tendency to decrease the mortality in septic shock animal and patients, especially when using a bolus administration, whereas studies using a continuous administration failed to find any benefit on mortality. The interest of the successive use of pro-oxidant action of seleno-compounds, followed by anti-oxidant action need to be the further studied in cellular and animal models, preceding new dose-effect phase II. The interest of the selenoprotein-P as a marker of septic shock and for endothelium protection needs also to be studied further.

译文

:硒有双重作用。 (i)硒化合物,其中亚硒酸钠具有直接的促氧化剂作用,导致急性毒性,但作为药物也可能是有益的。 (ii)硒是抗氧化硒酶所需的必需抗氧化剂。败血性休克是导致内皮损伤和多器官功能衰竭的常见严重综合症,数据增加提示氧化应激的主要作用。血浆中硒的主要成分硒蛋白P可能会急剧下降,尤其是在败血性休克患者中,并且可能参与了内皮保护。已对有感染证明的严重败血性休克患者进行了一项前瞻性,多中心,安慰剂对照,随机,双盲研究。患者连续10天接受硒作为亚硒酸钠(第一天为4000微克,第二天为9天为1000微克/天)或使用连续静脉输注的匹配安慰剂。在任何时候,两组之间的死亡率均无显着差异。两组的不良事件发生率相似。然而,高剂量硒的给药与降低败血性休克动物和患者死亡率的趋势有关,特别是在使用大剂量给药时,而使用连续给药的研究并未发现对死亡率有任何益处。在新的剂量效应阶段II之前,需要在细胞和动物模型中进一步研究硒化合物的促氧化作用相继使用以及随后的抗氧化作用。还需要进一步研究硒蛋白P作为败血性休克标志物和保护内皮的兴趣。

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