Polyethylene glycol-conjugated superoxide dismutase in focal cerebral ischemia-reperfusion.
Generation of free radicals during reperfusion after organ ischemia has been implicated in the pathogenesis of ischemic injury. We have previously shown that a combination of intravenous polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) and catalase (PEG-CAT), at a dose of 10,000 U/kg each, is effective in reducing infarct size in a focal cerebral ischemia model in the rat. It is not clear whether PEG-SOD alone is sufficient to reduce ischemic brain injury. In this study we determined the therapeutic efficacy of PEG-SOD and its dose-response curve. In a range of 1,000-30,000 U/kg, PEG-SOD exhibited a U-shaped dose-response curve. Only 10,000 U/kg significantly reduced infarct size [control 121 +/- 12 mm3 (mean +/- SE), n = 35; PEG-SOD 95 +/- 10 mm3, n = 36, P < 0.05]. PEG-SOD at the doses tested did not have significant acute hemodynamic effects but had a tendency to improve postischemic hypotension. This beneficial effect of PEG-SOD on blood pressure did not appear to fully account for the treatment effect of PEG-SOD on infarct size. The narrow therapeutic dose range of PEG-SOD in this study and similar findings of SOD in other investigations may contribute to the inconsistent protective effects of SOD preparations in ischemia-reperfusion injury in the literature.
He
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Division of Restorative Neurology, Baylor College of Medicine, Houston, Texas 77030.
Hsu
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Ezrin
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Miller
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D000818:Animals; D001794:Blood Pressure; D002545:Brain Ischemia / Q000097:blood / Q000473:pathology* / Q000503:physiopathology; D002544:Cerebral Infarction / Q000473:pathology; D016166:Free Radical Scavengers; D008297:Male; D011092:Polyethylene Glycols / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000097:blood / Q000473:pathology* / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000494:pharmacology*
D016166:Free Radical Scavengers; D011092:Polyethylene Glycols; D013482:Superoxide Dismutase; C063471:polyethylene glycol-superoxide dismutase