THE TOXICITY OF HIGH-DOSE SUPEROXIDE-DISMUTASE SUGGESTS THAT SUPEROXIDE CAN BOTH INITIATE AND TERMINATE LIPID-PEROXIDATION IN THE REPERFUSED HEART

Recently, we described an anomalous bell-shaped dose-response curve for the protection of the reoxygenated isolated myocardium by superoxide dismutase (SOD). (SOD)-S-19 is dramatically protective up to a point (5 mu/ml in the perfusate) beyond which it loses its ability to protect and, at very high doses (50 mu g/ml), exacerbates the injury. We proposed that O-2.(-) may serve as both initiator and terminator of lipid peroxidation, such that over scavenging the radical may increase net lipid peroxidation via increased chain length. We examined the ability of U74389F, a lipid peroxidation inhibitor, to ameliorate the toxicity of high-dose SOD in the isolated perfused rabbit heart preparation. The results show a significant improvement in the percent recovery of developed tension of hearts treated with U74389F and overdosed with MnSOD, as well as a decrease in thiobarbituric acid reactive substances.