Carbon Monoxide: from Poison to Clinical Trials.

Carbon Monoxide: from Poison to Clinical Trials.
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DOI:
10.1016/j.tips.2021.02.003
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发表时间:
2021-05
影响因子:
13.8
通讯作者:
Otterbein LE
Otterbein LE
中科院分区:
医学1区
文献类型:
--
作者:
Siracusa R;Schaufler A;Calabrese V;Fuller PM;Otterbein LE

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每个细胞都有一个高度复杂的系统来调节血红素水平,这对于周转而言尤其重要。血红素降解会产生一氧化碳 (CO),虽然 CO 长期以来一直被视为代谢废物,并且浓度较高时会导致细胞死亡,但我们现在知道 CO 是一种不可或缺的气体递质,参与生存所需的基本生理过程。无可辩驳的临床前数据促使人们齐心协力开发二氧化碳作为一种安全有效的治疗方法,但与这一观点相反的是,教条认为二氧化碳是一种毒物,尤其是对大脑来说。本文讨论了这场争论的出现,强调了 CO 通过其对中央生物钟的作用而具有神经保护特性,以及正在开发的用于临床使用的 CO 给药策略。
Every cell has a highly sophisticated system for regulating heme levels, which is particularly important with regard to turnover. Heme degradation generates carbon monoxide (CO) and while CO has long been viewed as a metabolic waste product, and at higher concentrations cellular lethal, we now know that CO is an indispensable gasotransmitter that participates in fundamental physiologic processes necessary for survival. Irrefutable preclinical data has resulted in concerted efforts to develop CO as a safe and effective therapeutic, but against this notion lies dogma that CO is a poison, especially to the brain. The emergence of this debate is discussed here highlighting the neuroprotective properties of CO through its role on the central circadian clock and ongoing strategies being developed for CO administration for clinical use.
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