TY - JOUR
T1 - Peroxynitrite
T2 - Biochemistry, pathophysiology and development of therapeutics
AU - Szabó, Csaba
AU - Ischiropoulos, Harry
AU - Radi, Rafael
N1 - Funding Information:
We thank V. Valez and D. Vitturi (Universidad de la República, Uruguay) for their contribution to the artwork. We also thank G. Ferrer-Sueta (Universidad de la República, Uruguay) for useful discussions. This work was supported by the NIH R01 GM060915 grant and the Oscar Asboth Project Grant from the National Office of Research and Technology, Budapest, Hungary to C.S.; HL54926, AG13966, ES013508 NIEHS Center of Excellence in Environmental Toxicology grants to H.I.; and The Howard Hughes Medical Institute and the International Centre of Genetic Engineering and Biotechnology grant to R.R. H.I. is the Gisela and Dennis Alter Chair in Pediatric Neonatology at the Children’s Hospital of Philadelphia. R.R. is a Howard Hughes International Research Scholar.
PY - 2007/8
Y1 - 2007/8
N2 - 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.
AB - 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.
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U2 - 10.1038/nrd2222
DO - 10.1038/nrd2222
M3 - Review article
C2 - 17667957
AN - SCOPUS:34547673497
SN - 1474-1776
VL - 6
SP - 662
EP - 680
JO - Nature Reviews Drug Discovery
JF - Nature Reviews Drug Discovery
IS - 8
ER -