Rinaldi S, Landucci F, De Gaudio A R
Department of Critical Care, University of Florence, 50134 Florence Italy.
Curr Drug Targets. 2009 Sep;10(9):872-80. doi: 10.2174/138945009789108774.
Critical illness and particularly sepsis are associated with a significant redox imbalance resulting from an increased production of oxidant species and a decrease in endogenous antioxidant defences. In critical patients sources of oxidative stress include the mitochondrial respiratory electron transport chain, xanthine oxidase activation, the respiratory burst associated with neutrophil activation, and arachidonic acid metabolism. Several endogenous antioxidants have been identified including enzymes, like superoxide dismutases and glutathione peroxidase, vitamins and other molecules such as uric acid and bilirubin. Recent studies pointed out the correlations between oxidative stress, systemic inflammatory response and apoptosis. Prospective randomized clinical trials regarding antioxidant therapy in critical illness provide increasing evidence in support of selenium, glutamine and omega-3 fatty acids. In particular selenium seems to improve clinical outcome in terms of infections and organ failure, glutamine has been associated with a significant reduction in infectious complications and omega-3 fatty acids could be particularly efficacious in sepsis. Melatonin is a promising molecule that deserves the attention of future research, as well as vitamin C. Further studied should also try to establish the more beneficial combination of antioxidants, as well as the doses, and the timing of administration. When such problems will be resolved hopefully results about antioxidant therapy in critical illness will be more univocal and promising.
危重病，尤其是脓毒症，与显著的氧化还原失衡有关，这是由于氧化剂生成增加和内源性抗氧化防御能力下降所致。在危重病患者中，氧化应激源包括线粒体呼吸电子传递链、黄嘌呤氧化酶激活、与中性粒细胞激活相关的呼吸爆发以及花生四烯酸代谢。已确定了几种内源性抗氧化剂，包括超氧化物歧化酶和谷胱甘肽过氧化物酶等酶、维生素以及尿酸和胆红素等其他分子。最近的研究指出了氧化应激、全身炎症反应和细胞凋亡之间的相关性。关于危重病抗氧化治疗的前瞻性随机临床试验提供了越来越多支持硒、谷氨酰胺和ω-3脂肪酸的证据。特别是硒似乎在感染和器官衰竭方面改善临床结局，谷氨酰胺与感染并发症显著减少有关，ω-3脂肪酸在脓毒症中可能特别有效。褪黑素是一种有前景的分子，值得未来研究关注，维生素C也是如此。进一步的研究还应尝试确定抗氧化剂更有益的组合、剂量以及给药时机。当这些问题得到解决时，有望关于危重病抗氧化治疗的结果将更加明确和有前景。
