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

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.

• Authors: Y Takeda, H Hashimoto, F Kosaka, M Hirakawa, M Inoue
• Journal: The American journal of physiology (Am J Physiol) Vol. 264 Issue 5 Pt 2 Pg. H1708-15 (May 1993) ISSN: 0002-9513 [Print] United States
• PMID: 8498583 (Publication Type: Journal Article)

Chemical References

• Polystyrenes
• Superoxide Dismutase
• superoxide dismutase-poly(styrene co-maleic acid butyl ester)

Topics

• Animals
• Blood-Brain Barrier (drug effects)
• Brain Injuries (mortality, pathology, prevention & control)
• Brain Ischemia (pathology)
• Cardiac Output (drug effects)
• Cerebrovascular Circulation (drug effects)
• Dogs
• Half-Life
• Injections, Intra-Arterial
• Intracranial Pressure (drug effects)
• Nervous System (drug effects, physiopathology)
• Polystyrenes (pharmacology)
• Reperfusion Injury (mortality, pathology, prevention & control)
• Superoxide Dismutase (pharmacology)
• Survival Analysis