Peroxynitrite generated at the level produced by spinal cord injury induces peroxidation of membrane phospholipids in normal rat cord: Reduction by a metalloporphyrin

Danxia Liu, Feng Bao, Donald S. Prough, Douglas S. DeWitt

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

The goal of the present study was to determine in vivo whether peroxynitrite, at the concentration and duration produced by SCI, contributes to membrane lipid peroxidation (MLP) after traumatic spinal cord injury (SCI) and the capability of a broad spectrum scavenger of reactive species, Mn (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP), to reduce MLP. This was accomplished by administering a peroxynitrite donor 3-morpholinosydnonimine (SIN-1) into the gray matter of an uninjured rat spinal cord through a microdialysis fiber to generate ONOO- at the SCI-elevated levels. The resulting MLP was characterized by measuring the productions of extracellular malondialdehyde and of intracellular 4-hydroxynonenal. We demonstrated that extracellular SIN-1 administration significantly increased the concentration of malondialdehyde (p < 0.001) and the numbers of hydroxynonenal-positive cells (p < 0.001) as compared to a control group in which ACSF was administered. Simultaneous administration of MnTBAP through a second microdialysis fiber significantly reduced SIN-1-induced malondialdehyde production (p < 0.001) and the numbers of HNE-positive cells (p < 0.001). There was no significant difference between MnTBAP-treated and ACSF-controls (p = 0.3). These results demonstrate in vivo that (1) SCI-produced levels of peroxynitrite sufficient to cause MLP, and therefore that peroxynitrite is an agent of secondary damage after acute SCI; (2) MnTBAP can efficiently reduce SIN-1-induced MLP.

Original languageEnglish (US)
Pages (from-to)1123-1133
Number of pages11
JournalJournal of neurotrauma
Volume22
Issue number10
DOIs
StatePublished - Oct 2005

Keywords

  • 3-morpholinosydnonimine
  • 4-hydroxynonenal
  • Malondialdehyde
  • Membrane lipid peroxidation
  • Mn (III) tetrakis (4-benzoic acid) porphyrin
  • Peroxynitrite
  • Secondary spinal cord injury

ASJC Scopus subject areas

  • Clinical Neurology

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