Department of Anesthesiology and Critical Care Medicine, University Medical Center, Freiburg, Germany.
Curr Pharm Biotechnol. 2012 May;13(6):837-50. doi: 10.2174/138920112800399103.
Carbon monoxide (CO) has long been considered a purely toxic by-product of incomplete combustion processes. Acute exposure to high concentrations of CO is one of the leading causes of fatal poisoning in industrial countries. However, after two decades of intensive research, there is ample evidence that CO endogenously produced by heme oxygenase enzymes has essential physiological functions and is of vital importance for cellular hemostasis. Furthermore, exogenously applied CO in low concentrations mediates potent cytoprotective effects. An overwhelming number of different in vitro and in vivo models demonstrated the protective action of CO application, e.g., in ischemia/reperfusion, transplantation, oxidative stress, inflammation, and others. Protection by this gaseous molecule could be illustrated for most organs, most species, and for different routes of administration. Now being on the verge of entering clinical trials, the question emerges whether the administration of low-dose CO would be safe for patients when used as a potential therapeutic. Therefore, this review summarizes in particular toxicological data obtained from low-dose CO exposure and discusses its impact on a possible clinical application.
一氧化碳（CO）长期以来一直被认为是不完全燃烧过程中产生的一种纯粹有毒的副产品。急性暴露于高浓度 CO 是工业国家致命中毒的主要原因之一。然而，经过二十年的深入研究，有充分的证据表明，血红素加氧酶产生的内源性 CO 具有重要的生理功能，对细胞止血至关重要。此外，低浓度的外源性 CO 可发挥有效的细胞保护作用。大量不同的体外和体内模型证明了 CO 应用的保护作用，例如在缺血/再灌注、移植、氧化应激、炎症等方面。这种气态分子的保护作用可以在大多数器官、大多数物种和不同的给药途径中得到说明。现在正处于临床试验的边缘，出现了一个问题，即当低剂量 CO 作为一种潜在的治疗方法使用时，对患者来说是否安全。因此，本综述特别总结了从低剂量 CO 暴露中获得的毒理学数据，并讨论了其对可能的临床应用的影响。
