Lecithinized Cu, Zn-superoxide dismutase limits the infarct size following ischemia-reperfusion injury in rat hearts in vivo.
Covalent binding of 4 molecules of phosphatidylcholine palmitoyl to human recombinant superoxide dismutase (SOD) results in a compound (lecithinized SOD) that has a longer half-life and greater affinity to the cell membrane than unmodified SOD. We investigated whether lecithinized SOD played a protective role against myocardial ischemia-reperfusion injuries in rats. Rats underwent 45 min of myocardial ischemia by occluding the left coronary artery followed by 120 min of reperfusion. They were randomly assigned to receive either lecithinized SOD, polyethylene glycol conjugated SOD (PEG-SOD), unmodified SOD, free lecithin derivative, or PBS intravenously at 5 min prior to reperfusion. Myocardial infarct area assessed by TTC staining was smaller in lecithinized SOD group than PEG-SOD, unmodified SOD, free lecithin derivative or control group. Blood pressure and heart rate was similar in each group. ELISA demonstrated SOD level in the heart was significantly high in lecithinized SOD group, especially in the heart of ischemia at risk. Although serum SOD level of PEG-SOD was as high as lecithinized SOD, SOD level of the heart was low. These data suggested lecithinized SOD had a protective effect in myocardial ischemia-reperfusion injuries through its increased bioavailability.
Hangaishi
M
M
Department of Cardiovascular Medicine, University of Tokyo, Tokyo, Japan.
Nakajima
H
H
Taguchi
J
J
Igarashi
R
R
Hoshino
J
J
Kurokawa
K
K
Kimura
S
S
Nagai
R
R
Ohno
M
M
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007275:Injections, Intravenous; D009203:Myocardial Infarction / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D010713:Phosphatidylcholines / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D014018:Tissue Distribution
D016166:Free Radical Scavengers; D010713:Phosphatidylcholines; D011092:Polyethylene Glycols; D013482:Superoxide Dismutase; C434045:lecithinized superoxide dismutase; C063471:polyethylene glycol-superoxide dismutase