ABSTRACT
Free radical pathology is closely connected with trace metal metabolism, especially that of iron. Superoxide-mediated injury to the heart occurs upon reoxygenation following ischemia or anoxic perfusion of the isolated organ. Much confusion exists in the literature regarding the role of superoxide in reperfusion injury caused by an adverse dose-response relationship exhibited by superoxide dismutase (SOD) both in vivo and in the isolated organ. Maximal protection against marker enzyme release, functional loss, or infarct size occurs at SOD concentrations between 1 and 10 µg/mL of perfusate. At SOD concentrations above this range, protection is progressively lost, and injury may be exacerbated. This is seen with both Cu,Zn-and Mn-SODs. The reason for this behavior is consistent with the concept that a crucial balance must be maintained between oxidants and antioxidants, and that the balance may be upset in either direction. I propose that in addition to being able to liberate iron and initiate lipid peroxidation, may also serve as a terminator of lipid peroxidation, that over-scavenging the radical may increase net lipid peroxidation. Studies combining the lipid peroxidation inhibitor U74389F with high-dose SOD support this view.
