Effects of a metalloporphyrinic peroxynitrite decomposition catalyst, ww-85, in a mouse model of spinal cord injury.

Abstract

The aim of the present study was to assess the effect of a metalloporphyrinic peroxynitrite decomposition catalyst, ww-85, in the pathophysiology of spinal cord injury (SCI) in mice. Spinal cord trauma was induced by the application of vascular clips to the dura via a four-level T5-T8 laminectomy. SCI in mice resulted in severe trauma characterized by oedema, neutrophil infiltration, production of inflammatory mediators, tissue damage and apoptosis. ww-85 treatment (30-300 microg/kg, i.p. 1 h after the SCI) significantly reduced in a dose-dependent manner: (1) the degree of spinal cord inflammation and tissue injury, (2) neutrophil infiltration (myeloperoxidase activity), (3) nitrotyrosine formation and PARP activation, (4) pro-inflammatory cytokines expression, (5) NF-kappaB activation and (6) apoptosis. Moreover, ww-85 significantly ameliorated the recovery of limb function (evaluated by motor recovery score) in a dose-dependent manner. The results demonstrate that ww-85 treatment reduces the development of inflammation and tissue injury associated with spinal cord trauma.

• Authors: Tiziana Genovese, Emanuela Mazzon, Emanuela Esposito, Rosanna Di Paola, Kanneganti Murthy, Lewis Neville, Placido Bramanti, Salvatore Cuzzocrea
• Journal: Free radical research (Free Radic Res) Vol. 43 Issue 7 Pg. 631-45 (Jul 2009) ISSN: 1029-2470 [Electronic] England
• PMID: 19418318 (Publication Type: Journal Article)

Chemical References

• Bax protein, mouse
• Cytokines
• NF-kappa B
• Proto-Oncogene Proteins c-bcl-2
• Thiobarbituric Acid Reactive Substances
• WW85 compound
• bcl-2-Associated X Protein
• Peroxynitrous Acid
• 3-nitrotyrosine
• Tyrosine
• Peroxidase
• Poly(ADP-ribose) Polymerases

Topics

• Animals
• Apoptosis (drug effects)
• Blotting, Western
• Cytokines (metabolism)
• Disease Models, Animal
• Immunoenzyme Techniques
• In Situ Nick-End Labeling
• Lipid Peroxidation (drug effects)
• Male
• Mice
• Motor Activity (drug effects)
• NF-kappa B (metabolism)
• Neutrophil Infiltration (drug effects)
• Peroxidase
• Peroxynitrous Acid (pharmacology)
• Poly(ADP-ribose) Polymerases (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Spinal Cord Injuries (drug therapy, metabolism)
• Thiobarbituric Acid Reactive Substances (metabolism)
• Tyrosine (analogs & derivatives, metabolism)
• bcl-2-Associated X Protein (metabolism)