Polyethylene glycol-conjugated superoxide dismutase in focal cerebral ischemia-reperfusion.

Abstract

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.

• Authors: Y Y He, C Y Hsu, A M Ezrin, M S Miller
• Journal: The American journal of physiology (Am J Physiol) Vol. 265 Issue 1 Pt 2 Pg. H252-6 (Jul 1993) ISSN: 0002-9513 [Print] United States
• PMID: 8342641 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Free Radical Scavengers
• Polyethylene Glycols
• Superoxide Dismutase
• polyethylene glycol-superoxide dismutase

Topics

• Animals
• Blood Pressure
• Brain Ischemia (blood, pathology, physiopathology)
• Cerebral Infarction (pathology)
• Free Radical Scavengers
• Male
• Polyethylene Glycols (pharmacology)
• Rats
• Rats, Inbred Strains
• Reperfusion Injury (blood, pathology, physiopathology)
• Superoxide Dismutase (pharmacology)