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-kappaB 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.
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Authors | Tiziana Genovese, Emanuela Mazzon, Emanuela Esposito, Carmelo Muià, Rosanna Di Paola, Placido Bramanti, Salvatore Cuzzocrea |
Journal | Free radical biology & medicine
(Free Radic Biol Med)
Vol. 43
Issue 5
Pg. 763-80
(Sep 01 2007)
ISSN: 0891-5849 [Print] United States |
PMID | 17664140
(Publication Type: Journal Article)
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Chemical References |
- I-kappa B Proteins
- Interleukin-1beta
- Interleukin-2
- Metalloporphyrins
- NF-kappa B
- Proto-Oncogene Proteins c-bcl-2
- Tumor Necrosis Factor-alpha
- iron(III)-tetrakis(p-sulfonatophenyl)porphyrin
- Peroxynitrous Acid
- 3-nitrotyrosine
- Tyrosine
- RNA
- DNA
- Peroxidase
- Poly(ADP-ribose) Polymerases
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Topics |
- Animals
- Catalysis
- DNA
(genetics)
- Disease Models, Animal
- I-kappa B Proteins
(metabolism)
- Interleukin-1beta
(metabolism)
- Interleukin-2
(metabolism)
- Lipid Peroxidation
(drug effects)
- Male
- Metalloporphyrins
(therapeutic use)
- Mice
- Mitochondria
(drug effects, genetics)
- NF-kappa B
(metabolism)
- Neutrophil Infiltration
(drug effects)
- Peroxidase
(metabolism)
- Peroxynitrous Acid
(metabolism)
- Phosphorylation
(drug effects)
- Poly(ADP-ribose) Polymerases
(metabolism)
- Protein Transport
- Proto-Oncogene Proteins c-bcl-2
(metabolism)
- RNA
(genetics)
- Spinal Cord Injuries
(drug therapy, metabolism)
- T-Lymphocytes
(metabolism)
- Tumor Necrosis Factor-alpha
(metabolism)
- Tyrosine
(analogs & derivatives, biosynthesis)
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