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Carbon monoxide in intensive care medicine—time to start the therapeutic application?!
Intensive Care Medicine Experimental Pub Date : 2020-01-09 , DOI: 10.1186/s40635-020-0292-8
Ulrich Goebel 1 , Jakob Wollborn 2
Affiliation  

Carbon monoxide (CO) is not only known as a toxic gas due to its characteristics as an odorless molecule and its rapid binding to haem-containing molecules, thus inhibiting the respiratory chain in cells resulting in hypoxia. For decades, scientists established evidence about its endogenously production in the breakdown of haem via haem-oxygenase (HO-1) and its physiological effects. Among these, the modulation of various systems inside the body are well described (e.g., anti-inflammatory, anti-oxidative, anti-apoptotic, and anti-proliferative). Carbon monoxide is able to modulate several extra- and intra-cellular signaling molecules leading to differentiated response according to the specific stimulus. With our growing understanding in the way CO exerts its effects, especially in the mitochondria and its intracellular pathways, it is tempting to speculate about a clinical application of this substance. Since HO-1 is not easy to induce, research focused on the application of the gaseous molecule CO by itself or the implementation of carbon monoxide releasing molecules (CO-RM) to deliver the molecule at a time- and dose dependently safe way to any target organ. After years of research in cellular systems and animal models, summing up data about safety issues as well as possible target to treat in various diseases, the first feasibility trials in humans were established. Up-to-date, safety issues have been cleared for low-dose carbon monoxide inhalation (up to 500 ppm), while there is no clinical data regarding the injection or intake of any kind of CO-RM so far. Current models of human research include sepsis, acute lung injury, and acute respiratory distress syndrome as well as acute kidney injury. Carbon monoxide is a most promising candidate in terms of a therapeutic agent to improve outbalanced organ conditions. In this paper, we summarized the current understanding of carbon monoxide’s biology and its possible organ targets to treating the critically ill patients in tomorrow’s ICU.

中文翻译:

重症监护医学中的一氧化碳——是时候开始治疗应用了?!

一氧化碳 (CO) 不仅是一种有毒气体,因为它具有无味分子的特性,并且可以与含血红素的分子快速结合,从而抑制细胞中的呼吸链,从而导致缺氧。几十年来,科学家们建立了关于其通过血红素加氧酶 (HO-1) 分解血红素的内源性产生及其生理效应的证据。其中,对体内各种系统的调节进行了很好的描述(例如,抗炎、抗氧化、抗凋亡和抗增殖)。一氧化碳能够调节多种细胞外和细胞内信号分子,导致根据特定刺激产生不同的反应。随着我们对 CO 发挥作用的方式越来越了解,特别是在线粒体及其细胞内途径中,人们很容易推测这种物质的临床应用。由于 HO-1 不易诱导,研究集中在气态分子 CO 本身的应用或实施一氧化碳释放分子 (CO-RM) 以时间和剂量依赖的安全方式将分子输送到任何靶器官。经过多年对细胞系统和动物模型的研究,总结了有关安全问题的数据以及各种疾病的可能治疗靶点,首次在人体中进行了可行性试验。迄今为止,低剂量一氧化碳吸入(高达 500 ppm)的安全问题已被清除,而目前还没有关于注射或摄入任何类型的 CO-RM 的临床数据。当前的人类研究模型包括败血症、急性肺损伤、和急性呼吸窘迫综合征以及急性肾损伤。就改善失衡器官状况的治疗剂而言,一氧化碳是最有希望的候选者。在本文中,我们总结了目前对一氧化碳生物学及其可能的器官靶点的理解,以治疗明天 ICU 中的危重患者。
更新日期:2020-01-09
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