The potential protective effects of erythropoietin and estrogen on renal ischemia reperfusion injury in ovariectomized rats

Peer review under responsibility of Alexandria University Faculty of Medicine.

Available online 30 December 2015

Abstract

Background

Renal ischemia–reperfusion (RIR) is an important etiopathological mechanism of acute renal failure (ARF). Erythropoietin (EPO) has been candidate as a nephroprotectant agent. However, its nephroprotective effect when it is accompanied with estrogen has not been studied in female.

Methods

Fifty-six female rats were divided into seven groups. Each formed of 8 rats. Group I: control group. Group II: Female rats exposed to RIR (named RIR group).Group III: Female rats exposed to RIR and pretreated with EPO (named RIR + EPO group). Group IV: ovariectomized rats exposed to RIR (named OVR + RIR group). Group V: ovariectomized rats received estrogen (E) then exposed to RIR (named OVR + RIR + E group). Group VI: ovariectomized rats received EPO before RIR (named OVR + RIR + EPO group). Group VII: ovariectomized rats received E then received EPO before RIR (named OVR + RIR + E + EPO group).Serum creatinine, blood urea nitrogen (BUN) and renal blood flow (RBF) were measured. Tumor necrosis factor-α (TNF-α), Myeloperoxidase activity (MPO), nitric oxide (NO), endothelin-1(ET-1) and EPO levels were assessed in the renal tissue. Histopathology was assessed to detect renal damage score.

Results

RIR significantly increased the serum levels of creatinine and BUN with decrease in RBF. In addition it significantly increased TNF-α, MPO and endothelin-1 levels with decrease in NO and EPO levels in renal tissue. However, these parameters significantly reversed by EPO except RBF. Combination of E and EPO leads to significant decrease in the protective effect of EPO.

Conclusion

It seems that EPO could protect the kidney against RIR, while this protective effect was decreased when E was supplemented.

Abbreviations:

• RIR
• renal ischemia–reperfusion
• ARF
• acute renal failure
• EPO
• erythropoietin
• E
• estrogen
• BUN
• blood urea nitrogen
• RBF
• renal blood flow
• TNF-α
• Tumor necrosis factor-α
• MPO
• Myeloperoxidase activity
• NO
• nitric oxide
• ET-1
• endothelin-1

Keywords:

• Renal ischemia–reperfusion
• Erythropoietin
• Estrogen
• Tumor necrosis factor-α
• Myeloperoxidase activity
• Nitric oxide

Acknowledgments

Our deep gratitude and appreciation to physiology and pharmacology departments for their help and support, as well as to pathology department, Faculty of Medicine, Benha University for valuable constructive cooperation in the histopathological part.

Notes

Peer review under responsibility of Alexandria University Faculty of Medicine.

Available online 30 December 2015