Albumin-binding superoxide dismutase with a prolonged half-life reduces reperfusion brain injury

Y. Takeda, H. Hashimoto, F. Kosaka, M. Hirakawa, M. Inoue

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

To test the possible involvement of superoxide radicals in the pathogenesis of reperfusion injury, we synthesized a superoxide dismutase (SOD) derivative [poly(styrene-co-maleic acid) butyl ester (SM) covalently linked to SOD] that circulates bound to albumin, has a prolonged in vivo half-life, and accumulates in pH-decreased tissues. The protective effects of SM-SOD on regional cerebral blood flow, intracranial pressure, cardiac index, vascular permeability, and neurological outcome were investigated using a model of global brain ischemia in dogs. Intra-arterial injection of SM-SOD (10 mg/kg) just before reperfusion increased reactive hyperemia (SM-SOD, 160 ± 36 ml · 100 g-1 · min-1 means ± SD, n = 6; control, 100 ± 34 ml · 100 g-1 · min-1, n = 6, P = 0.015), ameliorated delayed hypoperfusion (7 h after ischemia: SM-SOD, 40 ± 14 ml · 100 g-1 · min-1; control 17 ± 6 ml · 100 g-1 · min-1, P = 0.003), vascular permeability, and neurological outcome without affecting the cardiac index. These results indicate that superoxide radicals and/or their metabolite(s) might play a critical role in the pathogenesis of reperfusion injury in the brain.

Original languageEnglish
Pages (from-to)H1708-H1715
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume264
Issue number5 33-5
DOIs
Publication statusPublished - 1993

Keywords

  • blood-brain barrier
  • brain edema
  • cerebral blood flow
  • delayed hypoperfusion
  • free radical
  • global ischemia
  • neurological outcome

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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