Effects of a metalloporphyrinic peroxynitrite decomposition catalyst, ww-85, in a mouse model of spinal cord injury.
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.
IRCCS Centro Neurolesi Bonino-Pulejo, Messina, Italy.
Tiziana
T
Genovese
Emanuela
E
Mazzon
Emanuela
E
Esposito
Rosanna
R
Di Paola
Kanneganti
K
Murthy
Lewis
L
Neville
Placido
P
Bramanti
Salvatore
S
Cuzzocrea
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism*; D020556:Neutrophil Infiltration / Q000187:drug effects*; D009195:Peroxidase; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494827:Bax protein, mouse; D016207:Cytokines; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D017392:Thiobarbituric Acid Reactive Substances; C506898:WW85 compound; D051028:bcl-2-Associated X Protein; D030421:Peroxynitrous Acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D009195:Peroxidase; D011065:Poly(ADP-ribose) Polymerases