Polyethylene glycol-conjugated superoxide dismutase and catalase reduce ischemic brain injury.
Superoxide dismutase and catalase enzymatically scavenge superoxide and hydrogen peroxide, respectively. Conjugation of polyethylene glycol to superoxide dismutase (PEG-SOD) or catalase (PEG-CAT) prolongs the circulatory half-life of the native enzymes and enhances their intracellular access. We studied the protective effect of these free radical scavengers on ischemic brain injury using a rat model of focal cerebral ischemia, which is suitable for therapeutic trials. Intravenous administration of PEG-SOD (10,000 U/kg) and PEG-CAT (10,000 U/kg) before ischemia reduced the infarct volume (treatment, 139 +/- 9 mm3, means +/- SE, N = 38; placebo, 182 +/- 8 mm3, n = 37, P less than 0.002). This finding supports the concept that superoxide and hydrogen peroxide contribute to brain injury following focal cerebral ischemia.
Liu
T H
TH
Department of Neurology, Medical University of South Carolina, Charleston 29425-2232.
Beckman
J S
JS
Freeman
B A
BA
Hogan
E L
EL
Hsu
C Y
CY
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D002339:Carotid Arteries / Q000502:physiology; D002374:Catalase / Q000627:therapeutic use*; D002560:Cerebrovascular Circulation; D006339:Heart Rate / Q000187:drug effects; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D051381:Rats; D012016:Reference Values; D013482:Superoxide Dismutase / Q000627:therapeutic use*
C070295:catalase-polyethylene glycol; D002245:Carbon Dioxide; D011092:Polyethylene Glycols; D002374:Catalase; D013482:Superoxide Dismutase; C063471:polyethylene glycol-superoxide dismutase; D010100:Oxygen