Asialoerythropoietin has strong renoprotective effects against ischemia-reperfusion injury in a murine model.
BACKGROUND
The renoprotective effect of erythropoietin (EPO) and the nonhematopoietic EPO, asialoEPO was investigated in a murine ischemia-reperfusion injury (I/R) model.


METHODS
I/R was created by clamping the right renal pedicle for 60 min after left nephrectomy. Balb/c mice were divided into four groups (n=15 in each group): sham operation (Sham), vehicle treatment (Vehicle), EPO treatment (EPO), and asialoEPO treatment (AsialoEPO). EPO and asialoEPO were given at a dose of 500 IU/kg 30 min before I/R. Plasma creatinine (Cr), survival, and the number of apoptotic cells were analyzed. Protein expression was analyzed by Western blotting.


RESULTS
Plasma Cr level was not significantly different at 6 hr after I/R. At 24 hr after I/R, the Cr (mg/dL) levels in Sham, Vehicle, EPO, and asialoEPO were 0.13+/-0.01, 1.24+/-0.70, 0.24+/-0.08, and 0.25+/-0.13, respectively (P<0.05). The numbers of apoptotic cells in these groups were 0.1+/-0.1, 98.9+/-42.6, 3.3+/-0.7, and 2.9+/-1.6, respectively (P<0.05). Western blotting revealed that in kidney tissue of mice treated with EPO and asialoEPO, p38-MAPK and the proapoptotic molecule Bad was decreased, and the antiapoptotic molecules Bcl-xL and XIAP were increased. Survival rates at 7 days after I/R injury in the Sham, Vehicle, EPO, and AsialoEPO groups were 100%, 21.4%, 23.1%, and 53.8%, respectively (P=0.05).


CONCLUSIONS
EPO and asialoEPO attenuated renal dysfunction caused by I/R in mouse kidney at the same level, but only asialoEPO improved survival.
Okada
Toshie
T
Second Department of Surgery, Dokkyo University School of Medicine, Kitakobayashi 880, Mibu, Shimotsuga 880, Tochigi 321-0293, Japan.
Sawada
Tokihiko
T
Kubota
Keiichi
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001212:Asialoglycoproteins / Q000627:therapeutic use*; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011897:Random Allocation; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015996:Survival Rate; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000037:antagonists & inhibitors; D051020:bcl-X Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
D001212:Asialoglycoproteins; C494820:Bad protein, mouse; C494812:Bcl2l1 protein, mouse; D051636:X-Linked Inhibitor of Apoptosis Protein; C500605:asialoerythropoietin; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein; D004921:Erythropoietin; D003404:Creatinine; D048051:p38 Mitogen-Activated Protein Kinases