Reade Michael C, Fink Mitchell P
Austin Hospital/University of Melbourne, Heidelberg, Melbourne, Victoria, Australia.
Crit Care. 2005;9(6):556-60. doi: 10.1186/cc3892. Epub 2005 Oct 21.
Inflammation and oxidative stress cause renal impairment. Renal failure exacerbates the effect of oxidative stress on many organ systems. Antioxidants can prevent or treat renal failure in various experimental models and clinical situations. Pyruvate is an endogenous antioxidant with beneficial effects in animal models of oxidative stress. Because sodium pyruvate rapidly degrades in solution, a simple derivative of pyruvic acid, namely ethyl pyruvate, has been investigated as a therapeutic agent in preclinical studies. Ethyl pyruvate reduces organ system damage in ischaemia/reperfusion injury and haemorrhagic and endotoxic shock, at least in part through its antioxidant action. In addition, ethyl pyruvate appears to have direct beneficial effects on cytokine expression and proinflammatory gene regulation. The effect is long lasting and, importantly, even when it is administered after the onset of inflammation it can ameliorate organ damage and improve survival. Ethyl pyruvate is a widely used as a food additive and was shown to be safe in phase I clinical trials. We suggest ethyl pyruvate warrants further evaluation in the management of acute renal impairment.
炎症和氧化应激会导致肾功能损害。肾衰竭会加剧氧化应激对许多器官系统的影响。在各种实验模型和临床情况下，抗氧化剂可以预防或治疗肾衰竭。丙酮酸是一种内源性抗氧化剂，在氧化应激动物模型中具有有益作用。由于丙酮酸钠在溶液中会迅速降解，因此丙酮酸的一种简单衍生物，即丙酮酸乙酯，已在临床前研究中作为治疗剂进行了研究。丙酮酸乙酯至少部分通过其抗氧化作用减轻缺血/再灌注损伤以及出血性和内毒素性休克中的器官系统损伤。此外，丙酮酸乙酯似乎对细胞因子表达和促炎基因调控具有直接的有益作用。这种作用持久，重要的是，即使在炎症发作后给予，它也可以减轻器官损伤并提高存活率。丙酮酸乙酯被广泛用作食品添加剂，并且在I期临床试验中显示是安全的。我们建议丙酮酸乙酯在急性肾功能损害的管理中值得进一步评估。
