Peroxynitrite: biochemistry, pathophysiology and development of therapeutics.
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.
Szabó
Csaba
C
Department of Surgery, University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, University Heights, Newark, New Jersey 07103-2714, USA. szabocsaba@aol.com
Ischiropoulos
Harry
H
Radi
Rafael
R
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008665:Metalloporphyrins / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D008954:Models, Biological; D015394:Molecular Structure; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D030421:Peroxynitrous Acid / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*
D008665:Metalloporphyrins; D030421:Peroxynitrous Acid