Muscoli Carolina, Cuzzocrea Salvatore, Riley Dennis P, Zweier Jay L, Thiemermann Christoph, Wang Zhi-Qiang, Salvemini Daniela
Department of Biological and Pharmacological Research, MetaPhore Pharmaceuticals, 1910 Innerbelt Business Center Drive, St Louis, MO 63114, USA.
Br J Pharmacol. 2003 Oct;140(3):445-60. doi: 10.1038/sj.bjp.0705430.
The list of pathophysiological conditions associated with the overproduction of superoxide expands every day. Much of the knowledge compiled on the role of this radical in disease has been gathered using the native superoxide dismutase enzyme and, more recently, by the use of superoxide dismutase knockout models or transgenic models that overexpress the various isoforms of the enzyme. Although the native enzyme has shown promising anti-inflammatory properties in both preclinical and clinical studies, there were drawbacks and issues associated with its use as a therapeutic agent and pharmacological tool. Based on the concept that removal of superoxide modulates the course of inflammation, synthetic, low-molecular-weight mimetics of the superoxide dismutase enzymes that could overcome some of the limitations associated with the use of the native enzyme have been designed. In this review, we will discuss the advances made using various superoxide dismutase mimetics that led to the proposal that superoxide (and/or the product of its interaction with nitric oxide, peroxynitrite) is an important mediator of inflammation, and to the conclusion that superoxide dismutase mimetics can be utilized as therapeutic agents in diseases of various etiologies. The importance of the selectivity of such compounds in pharmacological studies will be discussed.
与超氧化物产生过多相关的病理生理状况清单日益增多。关于这种自由基在疾病中作用的许多知识是通过使用天然超氧化物歧化酶收集的，最近则是通过使用超氧化物歧化酶基因敲除模型或过表达该酶各种同工型的转基因模型收集的。尽管天然酶在临床前和临床研究中都显示出有前景的抗炎特性，但将其用作治疗剂和药理学工具存在缺点和问题。基于去除超氧化物可调节炎症进程这一概念，已设计出能克服与使用天然酶相关的一些局限性的超氧化物歧化酶合成低分子量模拟物。在本综述中，我们将讨论使用各种超氧化物歧化酶模拟物所取得的进展，这些进展促使人们提出超氧化物（和/或其与一氧化氮相互作用的产物，过氧亚硝酸盐）是炎症的重要介质，并得出超氧化物歧化酶模拟物可作为各种病因疾病的治疗剂的结论。还将讨论此类化合物在药理学研究中选择性的重要性。
