The cardioprotective effect of Mn-superoxide dismutase is lost at high doses in the postischemic isolated rabbit heart.

Abstract

The loss of protection by human recombinant (hr) Cu.Zn-superoxide dismutase (SOD) at higher doses reported previously may have been due to the weak peroxidase activity of this enzyme. To test this possibility we studied the dose-response relationship of hrMn-SOD, which lacks peroxidase activity. Isolated, buffer perfused rabbit hearts were subjected to 1 h of global ischemia followed by 1 h of reperfusion, and the percent recovery of developed tension (relative to preischemic) was measured via a left ventricular balloon connected through a pressure transducer to a polygraph recorder. The coronary effluent was assayed for lactate dehydrogenase (LDH) release. While hrMn-SOD almost completely protected against loss of function and LDH release at 2 and 5 mg/L (p less than 0.01), it exacerbated the damage at 50 mg/L concentration (p less than 0.05 against controls), thus giving an even sharper bell-shaped curve than seen with the hrCu,Zn-SOD. Therefore we conclude that, first, while the hrMn-SOD protects the reperfused heart at lower doses, it may exacerbate the damage at higher doses. Second, that the lack of protection seen at higher doses of hr-Cu,Zn-SOD is unlikely to be due only to its peroxidase activity.

• Authors: B A Omar, J M McCord
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 9 Issue 6 Pg. 473-8 ( 1990) ISSN: 0891-5849 [Print] United States
• PMID: 2079227 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Recombinant Proteins
• L-Lactate Dehydrogenase
• Superoxide Dismutase

Topics

• Animals
• Coronary Disease (drug therapy)
• Dose-Response Relationship, Drug
• L-Lactate Dehydrogenase (metabolism)
• Myocardial Reperfusion Injury (drug therapy)
• Rabbits
• Recombinant Proteins (administration & dosage, pharmacology)
• Superoxide Dismutase (administration & dosage, pharmacology)