Asialoerythropoietin has strong renoprotective effects against ischemia-reperfusion injury in a murine model.

Abstract

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).

CONCLUSION:

EPO and asialoEPO attenuated renal dysfunction caused by I/R in mouse kidney at the same level, but only asialoEPO improved survival.

• Authors: Toshie Okada, Tokihiko Sawada, Keiichi Kubota
• Journal: Transplantation (Transplantation) Vol. 84 Issue 4 Pg. 504-10 (Aug 27 2007) ISSN: 0041-1337 [Print] United States
• PMID: 17713435 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Asialoglycoproteins
• Bad protein, mouse
• Bcl2l1 protein, mouse
• X-Linked Inhibitor of Apoptosis Protein
• asialoerythropoietin
• bcl-Associated Death Protein
• bcl-X Protein
• Erythropoietin
• Creatinine
• p38 Mitogen-Activated Protein Kinases

Topics

• Animals
• Apoptosis (drug effects)
• Asialoglycoproteins (therapeutic use)
• Creatinine (blood)
• Disease Models, Animal
• Erythropoietin (analogs & derivatives, therapeutic use)
• Female
• Kidney (metabolism, pathology, physiopathology)
• Mice
• Mice, Inbred BALB C
• Random Allocation
• Reperfusion Injury (metabolism, pathology, prevention & control)
• Survival Rate
• X-Linked Inhibitor of Apoptosis Protein (metabolism)
• bcl-Associated Death Protein (antagonists & inhibitors)
• bcl-X Protein (metabolism)
• p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors)