Lecithinized copper, zinc-superoxide dismutase ameliorates ischemia-induced myocardial damage.
We have reported that lecithin-conjugated recombinant human Cu, Zn-superoxide dismutase (lecithinized SOD) has greater pharmacological potency than unmodified SOD through an increase in cell membrane affinity and half-life in plasma. Recently, ischemia or hypoxia alone has been suggested to result in increased superoxide anions, which lead to apoptosis in cardiomyocytes. We tested the effect of lecithinized SOD in reducing the infarct size following prolonged myocardial ischemia without reperfusion. Rats were subjected to a 24-h left coronary occlusion. Lecithinized SOD, unmodified SOD, free lecithin derivative or PBS was administered intravenously 30 min before coronary occlusion. SOD concentration of the heart, measured by ELISA, was higher in the lecithinized SOD-treated group than in the other groups 24 h after administration. The infarct area ratio of the heart, assessed by TTC staining, in the lecithinized SOD-treated group was significantly smaller than those of the other groups. Both TUNEL-positive cardiomyocytes and DNA laddering were attenuated in the ischemic area of the heart treated with lecithinized SOD. Single bolus administration of lecithinized SOD had a cardioprotective effect against ischemia without reperfusion in the rat model of acute myocardial infarction, possibly due to its sustained high tissue concentration.
Nakajima
H
H
Department of Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine, Japan.
Hangaishi
M
M
Ishizaka
N
N
Taguchi
J
J
Igarashi
R
R
Mizushima
Y
Y
Nagai
R
R
Ohno
M
M
D000818:Animals; D004247:DNA / Q000737:chemistry; D005260:Female; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics; D020287:In Situ Nick-End Labeling; D009203:Myocardial Infarction / Q000473:pathology*; D009206:Myocardium / Q000473:pathology*; D010713:Phosphatidylcholines; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism*
D010713:Phosphatidylcholines; D004247:DNA; D013482:Superoxide Dismutase