Lecithinized superoxide dismutase (PC-SOD) improved spinal cord injury-induced motor dysfunction through suppression of oxidative stress and enhancement of neurotrophic factor production

Mitsuko Takenaga, Yuki Ohta, Yukie Tokura, Akemi Hamaguchi, Masaya Nakamura, Hideyuki Okano, Rie Igarashi

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)283-289
Number of pages7
JournalJournal of Controlled Release
Volume110
Issue number2
DOIs
Publication statusPublished - 2006 Jan 10

Keywords

  • BBB (Basso Beattie Bresnahan) score
  • Lecithinized superoxide dismutase (PC-SOD)
  • Spinal cord injury (SCI)
  • Unmodified SOD (U-SOD)

ASJC Scopus subject areas

  • Pharmaceutical Science

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