Albumin-binding superoxide dismutase with a prolonged half-life reduces reperfusion brain injury
Takeda, Y.; Hashimoto, H.; Kosaka, F.; Hirakawa, M.; Inoue, M.
American Journal of Physiology 264(5 Pt 2): H1708-H1715
1993
ISSN/ISBN: 0002-9513 PMID: 8498583 Document Number: 412580
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 cntdot 100 g-1 cntdot min-1, means +- SD, n = 6; control, 100 +- 34 ml cntdot 100 g-1 cntdot min-1, n = 6, P = 0.015), ameliorated delayed hypoperfusion (7 h after ischemia: SM-SOD, 40 +- 14 ml cntdot 100 g-1 cntdot min-1; control 17 +- 6 ml cntdot 100 g-1 cntdot 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.