Multiple pathways of peroxynitrite cytotoxicity

Csaba Szabó

Research output: Contribution to journalArticlepeer-review

474 Scopus citations

Abstract

Peroxynitrite is a reactive oxidant produced from nitric oxide (NO) and superoxide, which reacts with a variety of biomolecules including proteins, lipids and DNA. Peroxynitrite is produced by the body in response to a variety of toxicologically relevant molecules including environmental toxins. It is also produced by the body in response to environmental toxins, as well as in reperfusion injury and inflammation. Here we overview the multiple pathways of peroxynitrite cytotoxicity. Initiation of lipid peroxidation, direct inhibition of mitochondrial respiratory chain enzymes, inactivation of glyceraldehyde-3-phosphate dehydrogenase, inhibition of membrane Na+/K+ ATP-ase activity, inactivation of membrane sodium channels, and other oxidative protein modifications contribute to the cytotoxic effect of peroxynitrite. In addition, peroxynitrite is a potent trigger of DNA strand breakage, with subsequent activation of the nuclear enzyme poly-ADP ribosyl synthetase or polymerase (PARP), with eventual severe energy depletion and necrosis of the cells. Studies conducted with peroxynitrite decomposition catalysts suggest that neutralization of peroxynitrite is of significant therapeutic benefit after exposure to various environmental toxins as well as in a variety of inflammatory and reperfusion disease conditions.

Original languageEnglish (US)
Pages (from-to)105-112
Number of pages8
JournalToxicology Letters
Volume140-141
DOIs
StatePublished - Apr 11 2003
Externally publishedYes

Keywords

  • Environmental toxins
  • Free radicals
  • Inflammation
  • Mitochondria
  • Nitric oxide
  • Superoxide

ASJC Scopus subject areas

  • Toxicology

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