On the selectivity of superoxide dismutase mimetics and its importance in pharmacological studies

Carolina Muscoli, Salvatore Cuzzocrea, Dennis P. Riley, Jay L. Zweier, Christoph Thiemermann, Zhi Qiang Wang, Daniela Salvemini

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)445-460
Number of pages16
JournalBritish Journal of Pharmacology
Volume140
Issue number3
DOIs
Publication statusPublished - Oct 2003

Keywords

  • Free radicals
  • Inflammation
  • Peroxynitrite
  • Superoxide
  • Superoxide dismutase mimetic

ASJC Scopus subject areas

  • Pharmacology

Fingerprint Dive into the research topics of 'On the selectivity of superoxide dismutase mimetics and its importance in pharmacological studies'. Together they form a unique fingerprint.

Cite this