Nitric Oxide and Peroxynitrite in Health and Disease

Pál Pacher; Joseph S. Beckman; Lucas Liaudet

doi:10.1152/physrev.00029.2006

journal article Jan 01, 2007

Nitric Oxide and Peroxynitrite in Health and Disease

Pál Pacher

Joseph S. Beckman

Lucas Liaudet

Physiological Reviews Vol. 87 No. 1 pp. 315-424 · American Physiological Society

View at Publisher Save 10.1152/physrev.00029.2006

Abstract

The discovery that mammalian cells have the ability to synthesize the free radical nitric oxide (NO) has stimulated an extraordinary impetus for scientific research in all the fields of biology and medicine. Since its early description as an endothelial-derived relaxing factor, NO has emerged as a fundamental signaling device regulating virtually every critical cellular function, as well as a potent mediator of cellular damage in a wide range of conditions. Recent evidence indicates that most of the cytotoxicity attributed to NO is rather due to peroxynitrite, produced from the diffusion-controlled reaction between NO and another free radical, the superoxide anion. Peroxynitrite interacts with lipids, DNA, and proteins via direct oxidative reactions or via indirect, radical-mediated mechanisms. These reactions trigger cellular responses ranging from subtle modulations of cell signaling to overwhelming oxidative injury, committing cells to necrosis or apoptosis. In vivo, peroxynitrite generation represents a crucial pathogenic mechanism in conditions such as stroke, myocardial infarction, chronic heart failure, diabetes, circulatory shock, chronic inflammatory diseases, cancer, and neurodegenerative disorders. Hence, novel pharmacological strategies aimed at removing peroxynitrite might represent powerful therapeutic tools in the future. Evidence supporting these novel roles of NO and peroxynitrite is presented in detail in this review.

Topics

No keywords indexed for this article. Browse by subject →

References

1,478

[1]

Abdelkarim GE, Gertz K, Harms C, Katchanov J, Dirnagl U, Szabo C, Endres M.Protective effects of PJ34, a novel, potent inhibitor of poly(ADP-ribose) polymerase (PARP) in in vitro and in vivo models of stroke.Int J Mol Med7: 255–260, 2001. 10.3892/ijmm.7.3.255

[2]

10.1161/01.str.26.8.1478

[3]

10.1016/0304-3940(95)12039-7

[4]

10.1080/01616412.1997.11740784

[5]

Abou-Mohamed G, Johnson JA, Jin L, El-Remessy AB, Do K, Kaesemeyer WH, Caldwell RB, Caldwell RW.Roles of superoxide, peroxynitrite, and protein kinase C in the development of tolerance to nitroglycerin.J Pharmacol Exp Ther308: 289–299, 2004. 10.1124/jpet.103.056119

[6]

10.1089/neu.2005.22.189

[7]

10.1152/ajpheart.01047.2002

[8]

10.1161/01.str.0000163111.05825.0b

[9]

Ahn B, Ohshima H.Suppression of intestinal polyposis in Apc(Min/+) mice by inhibiting NO production.Cancer Res61: 8357–8360, 2001.

[10]

10.1074/jbc.274.36.25821

[11]

10.1046/j.1525-1373.2000.22519.x

[12]

10.1054/plef.2001.0304

[13]

10.1096/fj.02-0130fje

[14]

10.1038/sj.bjp.0703280

[15]

10.1016/j.freeradbiomed.2004.06.006

[16]

10.1007/s00726-003-0018-8

[17]

10.1016/j.freeradbiomed.2004.06.034

[18]

Ambs S, Merriam WG, Bennett WP, Felley-Bosco E, Ogunfusika MO, Oser SM, Klein S, Shields PG, Billiar TR, Harris CC.Frequent NO synthase-2 expression in human colon adenomas: implication for tumor angiogenesis and colon cancer progression.Cancer Res58: 334–341, 1998.

[19]

10.1038/3957

[20]

10.1038/nrn1434

[21]

10.1016/j.psc.2004.10.001

[22]

10.1042/bj20031466

[23]

10.4049/jimmunol.170.4.2113

[24]

10.1038/415240a

[25]

10.1152/ajpheart.1989.256.5.h1440

[26]

Anversa P, Puntillo E, Olivetti G, Sonnenblick EH, Capasso JM.Load dependence of myocardial growth during maturation and aging.G Ital Cardiol19: 330–342, 1989.

[27]

10.1002/1531-8249(200004)47:4<524::aid-ana19>3.0.co;2-5

[28]

10.1073/pnas.95.13.7659

[29]

10.1002/bies.20370

[30]

10.1161/01.res.85.9.829

[31]

10.1016/s0014-5793(99)00073-3

[32]

10.1074/jbc.c200170200

[33]

10.2174/1567205043332162

[34]

Nitrogen dioxide and carbonate radical anion: two emerging radicals in biology

Ohara Augusto, Marcelo G. Bonini, Angélica M. Amanso et al.

Free Radical Biology and Medicine 10.1016/s0891-5849(02)00786-4

[35]

10.1073/pnas.221269198

[36]

10.1016/s0009-9120(00)00199-5

[37]

10.1016/s0008-6363(00)00091-2

[38]

10.1161/01.cir.99.14.1885

[39]

10.1096/fj.02-0530fje

[40]

10.1016/j.archger.2003.09.006

[41]

10.1073/pnas.92.26.12041

[42]

10.1161/hq0102.101127

[43]

10.1016/j.abb.2003.08.025

[44]

Bai P, Mabley JG, Liaudet L, Virag L, Szabo C, Pacher P.Matrix metalloproteinase activation is an early event in doxorubicin-induced cardiotoxicity.Oncol Rep11: 505–508, 2004. 10.3892/or.11.2.505

[45]

10.1016/j.yjmcc.2004.11.004

[46]

10.1124/jpet.103.052506

[47]

10.1007/s003950200050

[48]

10.1136/heart.87.1.77

[49]

10.1161/01.atv.19.3.646

[50]

10.1073/pnas.0402587101

Showing 50 of 1478 references

Cited By

5,257

Protective Action of Cerium Dioxide Nanoparticles on Human Serum Albumin in a Model of Nitrosative Stress

Madina M. Sozarukova, Arina D. Filippova · 2026

Russian Journal of General Chemistr...

Antioxidants and Exercise: A Redox-Informed Framework for Training Adaptation, Performance, and Recovery

Dan Cristian Mănescu, Andrei Tudor · 2026

Antioxidants

Pathophysiology of reactive oxygen species (ROS)

José Manuel Pérez de la Lastra, Celia María Curieses Andrés · 2026

Archives of Toxicology

Senescent hepatic stellate cells drive inflammation and disease progression in MASH (Review)

Zhiqi Han, Yiran She · 2026

Experimental and Therapeutic Medici...

Elamipretide in the Management of Barth Syndrome: Current Evidence and a Case Report

Neil Jacob, Daniel Schecter · 2025

Molecular Genetics and Metabolism

Antioxidants: a comprehensive review

İlhami Gulçin · 2025

Archives of Toxicology

Highly-sensitive photoacoustic gas sensor with dual resonant modalities for simultaneous NO and NO2 detection

Zhiyu Feng, Chaotan Sima · 2025

Sensors and Actuators B: Chemical

Free radicals and their impact on health and antioxidant defenses: a review

Nisansala Chandimali, Seon Gyeong Bak · 2025

Cell Death Discovery

Perspective on alcohol-induced organ damage via autophagy-dependent cellular changes

Ahmed Bakheet, Murugadas Anbazhagan · 2025

Redox Biology

Ferulic Acid Ameliorates L-Methionine-Induced Hyperhomocysteinemia in Rats

Sunita Bhise, Urmila Aswar · 2024

Drugs and Drug Candidates

Oxidative stress, free radicals and antioxidants: potential crosstalk in the pathophysiology of human diseases

Priya Chaudhary, Pracheta Janmeda · 2023

Frontiers in Chemistry

Kalanchoe sp. Extracts—Phytochemistry, Cytotoxic, and Antimicrobial Activities

Justyna Stefanowicz-Hajduk, Anna Hering · 2023

Plants

Novel tryptanthrin derivatives with benzenesulfonamide substituents: Design, synthesis, and anti-inflammatory evaluation

Jiyu Du, Peipei Liu · 2023

European Journal of Medicinal Chemi...

Cadmium cardiotoxicity is associated with oxidative stress and upregulated TLR-4/NF-kB pathway in rats; protective role of agomelatine

Reem S. Alruhaimi, Emad H.M. Hassanein · 2023

Food and Chemical Toxicology

Excited-state intramolecular proton transfer (ESIPT)-based fluorescent probes for biomarker detection: design, mechanism, and application

Hao Gu, Wenjing Wang · 2023

Chemical Communications

Modulating Plaque Inflammation via Targeted mRNA Nanoparticles for the Treatment of Atherosclerosis

Mingzhu Gao, Maoping Tang · 2023

ACS Nano

A CaCO3-based nanoplatform with sonodynamic and tumor microenvironment activated for combined in vitro cancer therapy

Jiale Cai, Guiping Hu · 2023

Translational Oncology

Betulinic acid protects against cardiotoxicity of the organophosphorus pesticide chlorpyrifos by suppressing oxidative stress, inflammation, and apoptosis in rats

Reem S. Alruhaimi · 2023

Environmental Science and Pollution...

One–pot synthesis of gold nanoparticles using Pandanus amaryllifolius leaf extract and their antibacterial, antioxidant, anticancer, and ecotoxicity assessment

Gopinath Kasi, Sarinthip Thanakkasaranee · 2023

Biocatalysis and Agricultural Biote...

The Synergy between Glutathione and Phenols—Phenolic Antioxidants Repair Glutathione: Closing the Virtuous Circle—A Theoretical Insight

Mirzam Carreon-Gonzalez, Juan Raúl Alvarez-Idaboy · 2023

Antioxidants

Metrics

5,257

Citations

1,478

References

Details

Published: Jan 01, 2007
Vol/Issue: 87(1)
Pages: 315-424

Authors

Department of Anesthesiology, The University of Alabama at Birmingham, Birmingham, Alabama 35233

L

Lucas Liaudet

Cite This Article

Pál Pacher, Joseph S. Beckman, Lucas Liaudet (2007). Nitric Oxide and Peroxynitrite in Health and Disease. Physiological Reviews, 87(1), 315-424. https://doi.org/10.1152/physrev.00029.2006

Nitric Oxide and Peroxynitrite in Health and Disease

You May Also Like