Lecithinized superoxide dismutase (PC-SOD) improved spinal cord injury-induced motor dysfunction through suppression of oxidative stress and enhancement of neurotrophic factor production.
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-1alpha 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 O2-, and suppressed neuronal death through reducing oxidative stress, increasing neuroprotective factor production and HIF-1alpha gene expression.
Takenaga
Mitsuko
M
Department of Frontier Medicine, Institute of Medical Science, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki 216-8512, Japan. Electronic address: m2take@marianna-u.ac.jp.
Ohta
Yuki
Y
Department of Frontier Medicine, Institute of Medical Science, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki 216-8512, Japan.
Tokura
Yukie
Y
Department of Frontier Medicine, Institute of Medical Science, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki 216-8512, Japan.
Hamaguchi
Akemi
A
Department of Frontier Medicine, Institute of Medical Science, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki 216-8512, Japan.
Nakamura
Masaya
M
Department of Orthopaedic Surgery, Keio University School of Medicine, 35 Shinano-cho, Shinjuku-ku, Tokyo 160-8582, Japan.
Okano
Hideyuki
H
Department of Physiology, Keio University School of Medicine, 35 Shinano-cho, Shinjuku-ku, Tokyo 160-8582, Japan.
Igarashi
Rie
R
Department of Frontier Medicine, Institute of Medical Science, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki 216-8512, Japan.
D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D004337:Drug Carriers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007150:Immunohistochemistry; D007553:Isotope Labeling; D015227:Lipid Peroxidation / Q000187:drug effects; D009069:Movement Disorders / Q000209:etiology / Q000517:prevention & control*; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D009474:Neurons / Q000187:drug effects; D009836:Oligodendroglia / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010713:Phosphatidylcholines / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013482:Superoxide Dismutase / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use*; D014018:Tissue Distribution
D018925:Chemokines; D016207:Cytokines; D004337:Drug Carriers; D009414:Nerve Growth Factors; D010713:Phosphatidylcholines; D013438:Sulfhydryl Compounds; D013482:Superoxide Dismutase