Effect of Apocynin, an inhibitor of NADPH oxidase, in the inflammatory process induced by an experimental model of spinal cord injury.
NADPH-oxidase is an enzyme responsible for reactive oxygen species production, and inhibition of this enzyme represents an attractive therapeutic target for the treatment of many diseases. The aim of this study was to investigate the effects of Apocynin, NADPH-oxidase inhibitor, in the modulation of secondary injury in the spinal cord. The injury was induced by application of vascular clips to the dura via a four-level T5-T8 laminectomy in mice. Treatment with Apocynin 1 and 6 h after the trauma significantly decreased (1) the degree of spinal cord inflammation and tissue injury, (2) neutrophil infiltration, (3) adhesion molecule expression, (4) nuclear transcription factor-κB expression, (5) nitrotyrosine and poly-ADP-ribose formation, (6) pro-inflammatory cytokines production, (7) apoptosis and (8) mitogen-activated protein kinase activation. Moreover, Apocynin significantly ameliorated the loss of limb function (evaluated by motor recovery score). Thus, it is proposed that Apocynin may be useful in the treatment of inflammation associated with spinal cord trauma.
Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Italy.
Daniela
D
Impellizzeri
Emanuela
E
Mazzon
Emanuela
E
Esposito
Irene
I
Paterniti
Placido
P
Bramanti
Salvatore
S
Cuzzocrea
D000098:Acetophenones / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D007150:Immunohistochemistry; D007796:Laminectomy; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D023421:Models, Animal; D009043:Motor Activity / Q000187:drug effects; D009187:Myelitis / Q000378:metabolism*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects; D015398:Signal Transduction; D013116:Spinal Cord / Q000378:metabolism / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D000098:Acetophenones; D015815:Cell Adhesion Molecules; D016207:Cytokines; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D011064:Poly Adenosine Diphosphate Ribose; C002744:3-nitrotyrosine; D014443:Tyrosine; C056165:acetovanillone; D019255:NADPH Oxidases; D020928:Mitogen-Activated Protein Kinases