Preconditioning with erythropoietin protects against subsequent ischemia-reperfusion injury in rat kidney

FASEB J. 2003 Sep;17(12):1754-5. doi: 10.1096/fj.02-1191fje. Epub 2003 Jul 18.


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.

MeSH terms

  • Animals
  • Apoptosis
  • Erythropoietin / therapeutic use*
  • HSP70 Heat-Shock Proteins / physiology
  • Ischemic Preconditioning
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Diseases / metabolism
  • Kidney Diseases / pathology
  • Kidney Diseases / prevention & control*
  • Mitogen-Activated Protein Kinases / metabolism
  • Models, Biological
  • Rats
  • Recombinant Proteins
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Signal Transduction


  • HSP70 Heat-Shock Proteins
  • Recombinant Proteins
  • Erythropoietin
  • Mitogen-Activated Protein Kinases