Albumin-binding superoxide dismutase with a prolonged half-life reduces reperfusion brain injury.
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.
Takeda
Y
Y
Department of Anesthesiology and Resuscitology, Okayama Medical School, Japan.
Hashimoto
H
H
Kosaka
F
F
Hirakawa
M
M
Inoue
M
M
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D001930:Brain Injuries / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D002545:Brain Ischemia / Q000473:pathology*; D002302:Cardiac Output / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004285:Dogs; D006207:Half-Life; D007269:Injections, Intra-Arterial; D007427:Intracranial Pressure / Q000187:drug effects; D009420:Nervous System / Q000187:drug effects / Q000503:physiopathology; D011137:Polystyrenes / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000494:pharmacology*; D016019:Survival Analysis
D011137:Polystyrenes; D013482:Superoxide Dismutase; C068153:superoxide dismutase-poly(styrene co-maleic acid butyl ester)