Cited by 97Redox biology and oxidative stressNitric Oxide and Endothelin EffectsAntioxidant Activity and Oxidative Stress

Peroxynitrite Detoxification and Its Biologic Implications

Trujillo, Madia, Ferrer-Sueta, Gerardo, Radi, Rafael·2008·Antioxidants & Redox Signaling

Abstract

Peroxynitrite is a cytotoxic oxidant formed in vivo from the diffusional-controlled reaction between nitric oxide and superoxide radicals. Increased peroxynitrite formation has been related to the pathogenesis of multiple diseases, thus underlining the importance of understanding the mechanisms of its detoxification. In nature, different enzymatic routes for peroxynitrite decomposition have evolved. Among them, peroxiredoxins catalytically reduce peroxynitrite in vitro; modulation of their expression affects peroxynitrite-mediated cytotoxicity, and their content changes in pathologic conditions associated with increased peroxynitrite formation in vivo, thus indicating a physiologic role of these enzymes in peroxynitrite reduction. Selenium-containing glutathione peroxidase also catalyzes peroxynitrite reduction, but its role in vivo is still a matter of debate. In selected cellular systems, heme proteins also play a role in peroxynitrite detoxification, such as its isomerization by oxyhemoglobin in red blood cells. Moreover, different pharmacologic approaches have been used to decrease the toxicity related to peroxynitrite formation. Manganese or iron porphyrins catalyze peroxynitrite decomposition, and their protective role in vivo has been confirmed in biologic systems. Glutathione peroxidase mimetics also rapidly reduce peroxynitrite, but their biologic role is less well established. Flavonoids, nitroxides, and tyrosine-containing peptides decreased peroxynitrite-mediated toxicity under different conditions, but their mechanism of action is indirect.

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Registry

Crossref · 10.1089/ars.2008.2060

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  • The fate of NO is dramatically changed in the presence of other free radicals such as superoxide.

    “Biologically, this means that the fate of NO is dramatically changed in the presence of other free radicals such as superoxide (O2˙̄) (2, 20–22).”
  • The presence of free radicals such as superoxide changes the fate of NO: once reacted, it forms peroxynitrite and can no longer bind to ferrous heme.

    “The presence of free radicals such as superoxide (O2.−) [82-85] changes the fate of NO: once reacted, it forms peroxynitrite [82, 84, 85] and can no longer bind to ferrous heme [86].”

    From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [83]

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Authors
Trujillo, M., Ferrer-Sueta, G., & Radi, R.
Affiliations
  • Universidad de la República de Uruguay (UY)
  • Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
  • Departamento de Bioquímica, Universidad de la República, Montevideo, Uruguay.
Venue
Antioxidants & Redox Signaling
Published
2008-09
Volume
10
Issue
9
Pages
1607-1620
ISSN
  • 1523-0864 (ISSN-L)
  • 1557-7716
OpenAlex
W2131163406
Cited by
97
References
146
Citations by year
2026: 3 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 9 · 2018: 7 · 2017: 5 · 2015: 9 · 2014: 7 · 2013: 4 · 2012: 3
FWCI
4.52
Type
journal article
Language
en
Open access
closed
Locations
  • Antioxidants and Redox Signaling (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Howard Hughes Medical Institute
  • International Centre for Genetic Engineering and Biotechnology
  • Comisión Nacional de Investigación Científica y Tecnológica
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
Keywords
peroxynitrite, peroxiredoxin, glutathione peroxidase, nitric oxide, superoxide, heme proteins, oxyhemoglobin, porphyrins, glutathione peroxidase mimetics, flavonoids, nitroxide radicals, tyrosine-containing peptides, cytotoxicity, oxidative stress
MeSH terms
Animals, Glutathione Peroxidase, Humans, Isomerism, Models, Biological, Nitrites, Oxidation-Reduction, Oxyhemoglobins, Peroxynitrous Acid, Peroxiredoxins

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