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金属配合物作为治疗缺血再灌注损伤的药物。

Metal Coordination Complexes as Therapeutic Agents for Ischemia-Reperfusion Injury.

作者信息

Bigham Nicholas P, Wilson Justin J

机构信息

Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, United States.

出版信息

J Am Chem Soc. 2023 May 3;145(17):9389-9409. doi: 10.1021/jacs.3c01984. Epub 2023 Apr 20.

Abstract

Ischemia-reperfusion injury (IRI), which describes the cell damage and death that occurs after blood and oxygen are restored to ischemic or hypoxic tissue, is a significant factor within the mortality rates of heart disease and stroke patients. At the cellular level, the return of oxygen triggers an increase in reactive oxygen species (ROS) and mitochondrial calcium (Ca) overload, which both contribute to cell death. Despite the widespread occurrence of IRI in different pathological conditions, there are currently no clinically approved therapeutic agents for its management. In this Perspective, we will briefly discuss the current therapeutic options for IRI and then describe in great detail the potential role and arising applications of metal-containing coordination and organometallic complexes for treating this condition. This Perspective categorizes these metal compounds based on their mechanisms of action, which include their use as delivery agents for gasotransmitters, inhibitors of Ca uptake, and catalysts for the decomposition of ROS. Lastly, the challenges and opportunities for inorganic chemistry approaches to manage IRI are discussed.

摘要

缺血再灌注损伤(IRI)是指血液和氧气恢复到缺血或缺氧组织后发生的细胞损伤和死亡,它是心脏病和中风患者死亡率的一个重要因素。在细胞水平上,氧气的恢复会触发活性氧(ROS)的增加和线粒体钙(Ca)超载,这两者都导致细胞死亡。尽管 IRI 在不同的病理条件下广泛发生,但目前尚无临床批准的治疗药物用于其治疗。在本观点中,我们将简要讨论 IRI 的当前治疗选择,然后详细描述含金属配位和金属有机配合物治疗这种疾病的潜在作用和新应用。本观点根据这些金属化合物的作用机制对其进行分类,这些机制包括它们作为气体递质传递剂、Ca 摄取抑制剂和 ROS 分解催化剂的应用。最后,讨论了无机化学方法管理 IRI 的挑战和机遇。

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Ischemia-reperfusion injury and volatile anesthetics.缺血再灌注损伤与挥发性麻醉剂
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