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Emerging pharmacological tools to control hydrogen sulfide signaling in critical illness
Intensive Care Medicine Experimental Pub Date : 2020-01-31 , DOI: 10.1186/s40635-020-0296-4
Eizo Marutani 1 , Fumito Ichinose 1
Affiliation  

Hydrogen sulfide (H 2 S) has long been known as a toxic environmental hazard. Discovery of physiological roles of H 2 S as a neurotransmitter by Kimura and colleagues triggered an intensive research in the biological roles of H 2 S in the past decades. Manipulation of H 2 S levels by inhibiting H 2 S synthesis or administration of H 2 S-releasing molecules revealed beneficial as well as harmful effects of H 2 S. As a result, it is now established that H 2 S levels are tightly controlled and too much or too little H 2 S levels cause harm. Nonetheless, translation of sulfide-based therapy to clinical practice has been stymied due to the very low therapeutic index of sulfide and the incomplete understanding of endogenous sulfide metabolism. One potential strategy to circumvent this problem is to use a safe and stable sulfide metabolite that may mediate effects of H 2 S. Alternatively, endogenous sulfide levels may be controlled using specific sulfide scavengers. In this review article, the role of endogenous H 2 S production and catabolism will be briefly reviewed followed by an introduction of thiosulfate and H 2 S scavengers as novel pharmacological tools to control H 2 S-dependent signaling.

中文翻译:

控制危重疾病中硫化氢信号传导的新兴药理学工具

硫化氢(H 2 S)长期以来被认为是一种有毒的环境危害。Kimura及其同事发现H 2 S作为神经递质的生理作用引发了过去几十年对H 2 S生物学作用的深入研究。通过抑制 H 2 S 合成或施用 H 2 S 释放分子来控制 H 2 S 水平,揭示了 H 2 S 的有益和有害作用。因此,现在已经确定,H 2 S 水平受到严格控制和控制。 H 2 S 含量过多或过少都会造成危害。尽管如此,由于硫化物的治疗指数非常低以及对内源性硫化物代谢的不完全了解,基于硫化物的疗法向临床实践的转化受到了阻碍。规避该问题的一种潜在策略是使用可以介导H 2 S作用的安全且稳定的硫化物代谢物。或者,可以使用特定的硫化物清除剂来控制内源硫化物水平。在这篇综述文章中,将简要回顾内源性 H 2 S 产生和分解代谢的作用,然后介绍硫代硫酸盐和 H 2 S 清除剂作为控制 H 2 S 依赖性信号传导的新型药理学工具。
更新日期:2020-01-31
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