Role of endogenous glutathione in the secondary damage in experimental spinal cord injury in mice.
GSH plays multiple roles in the nervous system including free radical scavenger, redox modulator of ionotropic receptor activity, and possible neurotransmitter. A lot of evidence suggests that GSH is involved in the pathogenesis of neurodegenerative disorders, like spinal cord injury (SCI). This study was undertaken to determine if the inhibition of endogenous glutathione, by L-buthionine-(S,R)-sulfoximine (BSO), affords protection against peroxynitrite-mediated toxicity in response to the spinal cord injury in vivo. The spinal cord of damaged animals showed a significant elevation of biochemical, immunohistochemical and functional parameters, increasing, respectively, neutrophils infiltration, lipid peroxidation, nitrotyrosine formation, PAR expression, apoptosis (measured by TUNEL staining) and loss of hind legs movement in SCI-operated mice. In contrast, the administration of BSO led to worsening of this already compromised setting, increasing the degree of (1) neutrophil infiltration, (2) lipid peroxidation, (3) histological damage, (4) apoptosis, (5) nitrotyrosine formation, (6) PAR expression, (7) apoptosis (measured by TUNEL staining) and (7) loss of hind legs movement. Thus, endogenous glutathione plays an important protective role against secondary damage after SCI.
Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Italy.
Tiziana
T
Genovese
Emanuela
E
Mazzon
Emanuela
E
Esposito
Carmelo
C
Muià
Rosanna
R
Di Paola
Paolo
P
Di Bella
Placido
P
Bramanti
Salvatore
S
Cuzzocrea
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D005978:Glutathione / Q000502:physiology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D020556:Neutrophil Infiltration / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis; D013117:Spinal Cord Compression / Q000473:pathology; D013119:Spinal Cord Injuries / Q000473:pathology*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000963:Antimetabolites; D051028:bcl-2-Associated X Protein; D011064:Poly Adenosine Diphosphate Ribose; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; D019328:Buthionine Sulfoximine; D012313:RNA; D004247:DNA; D009195:Peroxidase; D005978:Glutathione