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.