Lecithinized copper, zinc-superoxide dismutase ameliorates ischemia-induced myocardial damage

We have reported that lecithin-conjugated recombinant human Cu, Zn-superoxi de dismutase (lecithinized SOD) has greater pharmacological potency than un modified SOD through an increase in cell membrane affinity and half-life in plasma. Recently, ischemia or hypoxia alone has been suggested to result i n increased superoxide anions, which lead to apoptosis in cardiomyocytes. W e tested the effect of lecithinized SOD in reducing the infarct size follow ing prolonged myocardial ischemia without reperfusion. Rats were subjected to a 24-h left coronary occlusion. Lecithinized SOD, unmodified SOD, free l ecithin derivative or PBS was administered intravenously 30 min before coro nary occlusion. SOD concentration of the heart, measured by ELISA, was high er in the lecithinized SOD-treated group than in the other groups 24 h afte r administration. The infarct area ratio of the heart, assessed by TTC stai ning, in the lecithinized SOD-treated group was significantly smaller than those of the other groups. Both TUNEL-positive cardiomyocytes and DNA ladde ring were attenuated in the ischemic area of the heart treated with lecithi nized SOD. Single bolus administration of lecithinized SOD had a cardioprot ective effect against ischemia without reperfusion in the rat model of acut e myocardial infarction, possibly due to its sustained high tissue concentr ation. (C) 2001 Elsevier Science Inc. All rights reserved.