Renal protective effect of liposomed superoxide dismutase in an experimental warm ischemia model.
Superoxide dismutase (SOD) is a potent scavenger of superoxide radicals produced during normothermic ischemia-reperfusion. Since it has a short half-life, its optimal effect is achieved when it is given prior to reperfusion. The inclusion of SOD in liposomes (lipo-SOD) prolongs its half-life (free SOD: 6 min; lipo-SOD: 4 h). The protective effect of lipo-SOD in a 60-min bilateral renal warm ischemia model was studied. We divided 60 male Wistar rats between two control groups and five study groups according to the drug used (SOD or lipo-SOD) and to the time of SOD administration (prior to ischemia or prior to reperfusion). SOD and lipo-SOD were both given at 20 mg/kg endovenously. Weight, diuresis, creatinine per 100 g (Cr/100 g), and creatinine clearance per 100 g (CrCl/100 g) were studied. Conventional renal histology was performed after reperfusion and on day 7. Renal malondialdehyde, 6 keto PGF 1 alpha, and TxB2 tissue levels were studied after reperfusion. Results showed that the renal protective effect of free SOD on warm ischemic-reperfusion injury depended on the time of administration, being more effective when given before reperfusion. On the other hand, the renal protective effect of liposomed SOD did not depend on the time of administration since efficacy was similar when given before reperfusion or before ischemia. The functional protective effect of liposomed SOD was similar to that of free SOD when they were given prior to reperfusion. Nevertheless, since histological damage observed with liposomed SOD was less than with free SOD, it is suggested that the liposomed galenic form may offer better protection against renal warm ischemia. In addition, liposomed SOD was better at preventing tissue prostanoid generation after renal warm ischemic-reperfusion injury than free SOD. We concluded that liposomed SOD shows a higher renal protective effect against warm ischemia than free SOD.
Torras
J
J
Servei de Nefrología, Hospital de Bellvitge, Barcelona, Spain.
Seron
D
D
Herrero
I
I
Martinez-Castelao
A
A
Carrera
M
M
Alsina
J
J
Griño
J M
JM
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D003404:Creatinine / Q000097:blood; D004337:Drug Carriers; D016166:Free Radical Scavengers / Q000494:pharmacology; D007511:Ischemia / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply / Q000473:pathology / Q000502:physiology*; D008081:Liposomes; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D015427:Reperfusion Injury / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000378:metabolism
D004337:Drug Carriers; D016166:Free Radical Scavengers; D008081:Liposomes; D008315:Malondialdehyde; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D003404:Creatinine; D013482:Superoxide Dismutase