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

Abstract

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.

Donor treatment with a PHD-inhibitor activating HIFs prevents graft injury and prolongs survival in an allogenic kidney transplant model

“…(C) Blinded scoring for acute tubular necrosis revealed better preservation of renal morphology after FG-4497 compared with Veh independent of the immunological constellation ( * , P Ͻ 0.05). confirmed that a number of genes previously identified as HIF-dependent are inducible in the kidney, including EPO, which has previously been demonstrated to be nephroprotective in renal ischemia-reperfusion models (30)(31)(32)(33), and HO-1, which has also been shown to improve short-and long-term graft function in the same rat model (34,35). In addition, HIF activation facilitates cellular anaerobic metabolism by inducing Glut-1 or enzymes involved in glycolysis.…”

Erythropoietin ameliorates genetamicin-induced renal toxicity: A biochemical and histopathological study

“…Similarly, its renoprotective effect in ischemia-reperfusion renal injury, as the most common cause of ARF in the community was also reported (15,31). It seems that erythropoietin is not solely a hormone charged with regulating the proliferation and differentiation of erythroid progenitor cells (33,34). Its erythropoietic function is mediated by antiapoptotic pathways, mainly involving Akt and the Bcl-2 gene family in bone marrow.…”

Erythropoietin as an antiapoptotic, tissue-protective cytokine

“…72 The kidney is protected by EPO in the setting of both ischemic and toxic injuries. [73][74][75] In ischemic injury with reperfusion, EPO prevents apoptosis of tubular epithelial cells as well as mediates intense mitotic activity of the surviving population of proximal tubular epithelial cells. 73 The skin has also been shown to be protected by EPO in rodent flap models.…”