Beneficial effects of FeTSPP, a peroxynitrite decomposition catalyst, in a mouse model of spinal cord injury

Tiziana Genovese, Emanuela Mazzon, Emanuela Esposito, Carmelo Muià, Rosanna Di Paola, Placido Bramanti, Salvatore Cuzzocrea

Research output: Contribution to journalArticlepeer-review

Abstract

The aim of the present study was to assess the contribution of peroxynitrite formation in the pathophysiology of spinal cord injury (SCI) in mice. To this purpose, we used a peroxynitrite decomposition catalyst, 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato iron III chloride (FeTSPP). Spinal cord trauma was induced by the application of vascular clips (force of 24g) to the dura via a four-level T5-T8 laminectomy. SCI in mice resulted in severe trauma characterized by edema, neutrophil infiltration, production of inflammatory mediators, tissue damage, and apoptosis. FeTSPP treatment (10-100 mg/kg, i.p.) significantly reduced in dose-dependent manner 1 and 4 h after the SCI (1) the degree of spinal cord inflammation and tissue injury (histological score), (2) neutrophil infiltration (myeloperoxidase activity), (3) nitrotyrosine formation and poly-(ADP-ribose) polymerase activation, (4) proinflammmaory cytokines expression, (5) NF-κB activation, and (6) apoptosis (TUNEL staining, Bax and Bcl-2 expression). Moreover, FeTSPP significantly ameliorated the recovery of limb function (evaluated by motor recovery score) in a dose-dependent manner. Taken together, our results clearly demonstrate that FeTSPP treatment reduces the development of inflammation and tissue injury associated with spinal cord trauma similarly to dexamethasone, a well-known antiinflammatory agent which we have used as positive control.

Original languageEnglish
Pages (from-to)763-780
Number of pages18
JournalFree Radical Biology and Medicine
Volume43
Issue number5
DOIs
Publication statusPublished - Sep 1 2007

Keywords

  • FeTSPP
  • Peroxynitrite
  • Spinal cord injury

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

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