Beneficial effects of FeTSPP, a peroxynitrite decomposition catalyst, in a mouse model of spinal cord injury.
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.
Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, 98100 Messina, Italy.
Tiziana
T
Genovese
Emanuela
E
Mazzon
Emanuela
E
Esposito
Carmelo
C
Muià
Rosanna
R
Di Paola
Placido
P
Bramanti
Salvatore
S
Cuzzocrea
D000818:Animals; D002384:Catalysis; D004247:DNA / Q000235:genetics; D004195:Disease Models, Animal; D020672:I-kappa B Proteins / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008665:Metalloporphyrins / Q000627:therapeutic use*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D021381:Protein Transport; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012313:RNA / Q000235:genetics; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000096:biosynthesis
D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D007376:Interleukin-2; D008665:Metalloporphyrins; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; C510472:iron(III)-tetrakis(p-sulfonatophenyl)porphyrin; D030421:Peroxynitrous Acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D012313:RNA; D004247:DNA; D009195:Peroxidase; D011065:Poly(ADP-ribose) Polymerases