Erythropoietin attenuates renal injury in an experimental model of rat unilateral ureteral obstruction via anti-inflammatory and anti-apoptotic effects.
OBJECTIVE
Erythropoietin was recently shown to exert important cytoprotective and anti-apoptotic effects in injury models of the brain, heart and kidney. We examined whether erythropoietin also attenuates renal injury in a rat model of unilateral ureteral obstruction via anti-apoptotic and anti-inflammatory actions.


METHODS
We divided Sprague-Dawley rats (Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea) into 4 groups, including 1-vehicle treated with sham operation, 2-vehicle treated with unilateral ureteral obstruction for 3 days, 3-erythropoietin treatment with sham operation and 4-erythropoietin treatment for unilateral ureteral obstruction for 3 days. The erythropoietin treatment dose was 3,000 IU/kg per day intraperitoneally, administered daily. We compared competitive reverse transcriptase-polymerase chain reaction data on transforming growth factor-beta, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, osteopontin, Fas and Bcl-2. Furthermore, we examined Western blots for caspase-3 and light microscopy findings with hematoxylin and eosin staining. We applied immunohistochemistry for transforming growth factor-beta, ED-1 and caspase-3, and TUNEL in each group.


RESULTS
Transforming growth factor-beta, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, osteopontin and Fas mRNA levels in the erythropoietin treated, unilateral ureteral obstruction group were significantly lower than in the obstruction only group. The Bcl-2 mRNA level in the erythropoietin treated obstruction group was significantly higher than in the obstruction only group. Caspase-3 activity in the erythropoietin treated obstruction group was significantly lower than in the obstruction only group. On light microscopy interstitially infiltrated inflammatory cells were significantly decreased in the erythropoietin treated obstruction group compared to the obstruction only group. On immunohistochemistry the erythropoietin treated obstruction group showed significantly fewer reactions for transforming growth factor-beta, ED-1 and caspase-3 compared to the obstruction only group. Erythropoietin treatment in rats with unilateral ureteral obstruction significantly decreased the number of TUNEL positive cells.


CONCLUSIONS
Erythropoietin exerts renoprotective effects in an experimental unilateral ureteral obstruction rat model via anti-apoptotic and anti-inflammatory actions.
Chang
Yoon-Kyung
YK
Department of Nephrology, Catholic University Daejeon St. Mary Hospital, Daejeon, Republic of Korea.
Choi
Dae Eun
DE
Na
Ki-Ryang
KR
Lee
Sang-Ju
SJ
Suh
Kwang-Sun
KS
Kim
Suk Young
SY
Shin
Young-Tai
YT
Lee
Kang Wook
KW
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy; D007674:Kidney Diseases / Q000209:etiology* / Q000517:prevention & control*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014517:Ureteral Obstruction / Q000150:complications*
D004921:Erythropoietin