Peroxynitrite: Biochemistry, Pathophysiology and Development of Therapeutics

Nat Rev Drug Discov. 2007 Aug;6(8):662-80. doi: 10.1038/nrd2222.

Abstract

Peroxynitrite--the product of the diffusion-controlled reaction of nitric oxide with superoxide radical--is a short-lived oxidant species that is a potent inducer of cell death. Conditions in which the reaction products of peroxynitrite have been detected and in which pharmacological inhibition of its formation or its decomposition have been shown to be of benefit include vascular diseases, ischaemia-reperfusion injury, circulatory shock, inflammation, pain and neurodegeneration. In this Review, we first discuss the biochemistry and pathophysiology of peroxynitrite and then focus on pharmacological strategies to attenuate the toxic effects of peroxynitrite. These include its catalytic reduction to nitrite and its isomerization to nitrate by metalloporphyrins, which have led to potential candidates for drug development for cardiovascular, inflammatory and neurodegenerative diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / physiopathology
  • Humans
  • Metalloporphyrins / chemistry
  • Metalloporphyrins / metabolism*
  • Metalloporphyrins / therapeutic use
  • Models, Biological
  • Molecular Structure
  • Neurodegenerative Diseases / drug therapy
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / physiopathology
  • Peroxynitrous Acid / antagonists & inhibitors
  • Peroxynitrous Acid / chemistry
  • Peroxynitrous Acid / metabolism*

Substances

  • Metalloporphyrins
  • Peroxynitrous Acid