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Preconditioning with erythropoietin protects against subsequent ischemia‐reperfusion injury in rat kidney
Author(s) -
Yang Chul Woo,
Li Can,
Young Jung Ju,
Shin Seok Joon,
Choi Bum Soon,
Lim Sun Woo,
Sun Bo Kyung,
Kim Yong Soo,
Kim Jin,
Chang Yoon Sik,
Bang Byung Kee
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-1191fje
Subject(s) - erythropoietin , medicine , tunel assay , apoptosis , hsp70 , kidney , ischemia , reperfusion injury , pharmacology , acute kidney injury , renal ischemia , necrosis , creatinine , endocrinology , heat shock protein , immunohistochemistry , chemistry , biochemistry , gene
Improving the ability of the kidney to tolerate ischemic injury has important implications. We investigated the effect of recombinant human erythropoietin (rHuEPO) treatment on subsequent ischemia/reperfusion (I/R) injury and evaluated the role of heat shock protein (HSP) 70 in rHuEPO‐induced renal protection. rHuEPO (3000 U/kg) was administered 24 h before I/R injury, and rats were killed at 24, 48, and 72 h after I/R injury. Pretreatment of rHuEPO resulted in the following: i) decreased serum creatinine level; ii) decreased tubular cell apoptosis and necrosis, measured by DNA fragmentation analysis and TUNEL staining and histomorphological criteria; iii) decreased tubular cell proliferation as determined by proliferating cell nuclear antigen expression; iv) increased bcl‐2 protein and decreased caspase 3 activity; and v) decreased JNK expression. rHuEPO treatment increased HSP70 expression in a dose‐dependent manner in normal rat kidneys, and inhibition of HSP70 expression by quercetin eliminated the renoprotective effect of rHuEPO in ischemic kidneys. Our study demonstrates that rHuEPO has a protective effect on subsequent I/R injury and that this effect is associated with induction of HSP70. Our study provides a new avenue for therapy to prevent renal damage after I/R injury.

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