TY - JOUR
T1 - Lecithinized superoxide dismutase (PC-SOD) improved spinal cord injury-induced motor dysfunction through suppression of oxidative stress and enhancement of neurotrophic factor production
AU - Takenaga, Mitsuko
AU - Ohta, Yuki
AU - Tokura, Yukie
AU - Hamaguchi, Akemi
AU - Nakamura, Masaya
AU - Okano, Hideyuki
AU - Igarashi, Rie
PY - 2006/1/10
Y1 - 2006/1/10
N2 - PC-SOD (lecithinized superoxide dismutase) is a derivative of human Cu, Zn-SOD conjugated with 4 molecules of lecithin, yet having the enzyme activity of scavenging superoxide anion (O2-). Intravenous administration of PC-SOD promoted the recovery from spinal cord injury (SCI)-induced motor dysfunction in a dose-dependent manner in rat model, when evaluated by BBB (Basso Beattie Bresnahan) score. Even when given at 24 h after SCI, PC-SOD (1 mg/kg) significantly improved motor dysfunction. Distribution study demonstrated that PC-SOD gradually accumulated to the injured site. Enzyme-linked immunoassay revealed that PC-SOD prevented quantitative loss of neurons, astrocytes, and oligodendrocytes. PC-SOD inhibited SCI-induced oxidative stress, such as the decrease of free sulfhydryl residue, acetylcholine esterase activity, and the increase of lipid peroxidation. PC-SOD increased the production of neuroprotective factors. HIF-1α gene expression increased following SCI, and PC-SOD further increased it. In conclusion, PC-SOD gradually accumulated and retained at the damaged site to scavenge excessive O 2-, and suppressed neuronal death through reducing oxidative stress, increasing neuroprotective factor production and HIF-1α gene expression.
AB - PC-SOD (lecithinized superoxide dismutase) is a derivative of human Cu, Zn-SOD conjugated with 4 molecules of lecithin, yet having the enzyme activity of scavenging superoxide anion (O2-). Intravenous administration of PC-SOD promoted the recovery from spinal cord injury (SCI)-induced motor dysfunction in a dose-dependent manner in rat model, when evaluated by BBB (Basso Beattie Bresnahan) score. Even when given at 24 h after SCI, PC-SOD (1 mg/kg) significantly improved motor dysfunction. Distribution study demonstrated that PC-SOD gradually accumulated to the injured site. Enzyme-linked immunoassay revealed that PC-SOD prevented quantitative loss of neurons, astrocytes, and oligodendrocytes. PC-SOD inhibited SCI-induced oxidative stress, such as the decrease of free sulfhydryl residue, acetylcholine esterase activity, and the increase of lipid peroxidation. PC-SOD increased the production of neuroprotective factors. HIF-1α gene expression increased following SCI, and PC-SOD further increased it. In conclusion, PC-SOD gradually accumulated and retained at the damaged site to scavenge excessive O 2-, and suppressed neuronal death through reducing oxidative stress, increasing neuroprotective factor production and HIF-1α gene expression.
KW - BBB (Basso Beattie Bresnahan) score
KW - Lecithinized superoxide dismutase (PC-SOD)
KW - Spinal cord injury (SCI)
KW - Unmodified SOD (U-SOD)
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UR - http://www.scopus.com/inward/citedby.url?scp=29244484263&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2005.10.022
DO - 10.1016/j.jconrel.2005.10.022
M3 - Article
C2 - 16332351
AN - SCOPUS:29244484263
VL - 110
SP - 283
EP - 289
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
IS - 2
ER -