Use of carbon monoxide as a therapeutic agent: promises and challenges
Use of carbon monoxide as a therapeutic agent: promises and challenges
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DOI：
10.1007/s00134-008-1011-1
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发表时间：
2008-04-01
影响因子：
38.9
通讯作者：
Motterlini, Roberto
中科院分区：
文献类型：
--
作者：
Foresti, Roberta;Bani-Hani, Mohamed G.;Motterlini, Roberto
作为血红素加氧酶系统血红素分解代谢的副产物，一氧化碳（CO）多年来一直被忽视，直到最近才认识到它作为一种重要的信号分子的作用。在过去的十年中，在疾病的临床前实验模型中使用CO气体已经产生了一些显著的数据，表明将其治疗性地传递给哺乳动物可以减轻炎症过程和心血管疾病。然而，一氧化碳固有的毒性不可忽视，吸入不受控制的这种气体最终会导致严重的全身并发症和神经紊乱。从临床角度来看，一个关键的问题是，是否可以在器官和组织局部达到安全且治疗有效的一氧化碳阈值，而不通过肺部输送潜在的毒性量。CO释放分子（CO- rms）是一组能够在细胞系统中携带和释放一定量CO的化合物，它的出现似乎是克服CO气体限制的一种可行的替代方法。尽管CO-RMs技术还处于起步阶段，远未用于临床应用，但它得到了非常令人鼓舞的生物学结果的支持，并反映在这些化合物的化学多功能性以及它们转化为co基药物的无限潜力上。
As a by-product of heme catabolism by the heme oxygenase system, carbon monoxide (CO) has been neglected for many years, and only recently has its role as an essential signaling molecule been appreciated. In the past decade, the use of CO gas in pre-clinical experimental models of disease has produced some remarkable data indicating that its therapeutic delivery to mammals could alleviate inflammatory processes and cardiovascular disorders. However, the inherent toxic nature of CO cannot be ignored, knowing that inhalation of uncontrolled amounts of this gas can ultimately lead to serious systemic complications and neuronal derangements. From a clinical perspective, a key question is whether a safe and therapeutically effective threshold of CO can be reached locally in organs and tissues without delivering potentially toxic amounts through the lung. The advent of CO-releasing molecules (CO-RMs), a group of compounds capable of carrying and liberating controlled quantities of CO in cellular systems, appears a plausible alternative in the attempt to overcome the limitations of CO gas. Although in its infancy and far from being used for clinical applications, the CO-RMs technology is supported by very encouraging biological results and reflected by the chemical versatility of these compounds and their endless potential to be transformed into CO-based pharmaceuticals.