Effects of combined erythropoietin and epidermal growth factor on renal ischaemia/reperfusion injury: a randomized experimental controlled study

• Published in: BJU international Vol. 107; no. 2; pp. 323 - 328
• Main Authors: Hussein, Abd El‐Aziz M., Shokeir, Ahmed A., Sarhan, Mohammed E., El‐Menabawy, Fayza R., Abd‐Elmoneim, Hanaa A., El‐Nashar, Eman M., Barakat, Nashwa M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-01-2011; Wiley-Blackwell
• Subjects: Analysis of Variance; Animals; Antioxidants - therapeutic use; Biological and medical sciences; Drug Therapy, Combination; EGF; Epidermal Growth Factor - therapeutic use; erythropoietin; Erythropoietin - therapeutic use; GSH; ischaemia/reperfusion injury; kidney; Kidney - pathology; Male; MDA; Medical sciences; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Random Allocation; rat; Rats; Rats, Sprague-Dawley; Renovascular diseases; Reperfusion Injury - etiology; Reperfusion Injury - pathology; Reperfusion Injury - prevention & control; SOD; Kidney disease; Nephrology; ischaemia/reperfusion injury; Urinary system disease; Erythropoietin; Rat; EGF; Rodentia; Cardiovascular disease; SOD; MDA; Experimental study; Urology; Vascular disease; Prevention; kidney; Vertebrata; Randomization; Mammalia; Epidermal growth factor; Polypeptide; Animal; Renal ischemia reperfusion injury; GSH
• ISSN: 1464-4096; 1464-410X
• DOI: 10.1111/j.1464-410X.2010.09328.x

What’s known on the subject? and What does the study add?
It is well known that erythropoietin (EPO) ameliorates the renal injury induced by ischemia or toxins such as cisplatin and radiocontrast media. Also, epidermal growth factor (EGF) exerts a prophylactic nephroprotective effect against the deleterious consequences of the ischemia/reperfusion (I/R) injury. Nevertheless, the combined effect of both drugs remains to be further investigated.
This study examined the protective effects of EPO and EGF alone and in combination against renal I/R injury and showed that EPO alone was more powerful than EGF alone and the combination of both drugs was more protective than each agent alone.
OBJECTIVE
To investigate effects of combination of erythropoietin (EPO) and epidermal growth factor (EGF) on renal ischaemia and on reactive oxygen species in a rat model.
MATERIALS AND METHODS
In all, 90 male Sprague‐Dawley rats were allocated into five groups of 18, designated: Sham; treated with right nephrectomy only; Control, subjected to left renal ischaemia for 45 min with no treatment; EPO‐treated, as the control but with EPO pretreatment; EGF‐treated, as the control but with EGF pretreatment; EPO + EGF‐treated, as the control but with EPO and EGF pretreatment. Renal function, histopathology and malondialdehyde (MDA), superoxide dismutase (SOD) and reduced glutathione (GSH) levels in kidneys were assessed at 1, 2 and 7 days after ischaemia.
RESULTS
All rats except the controls had a significant improvement in serum creatinine, creatinine clearance and fractional excretion of Na+; all three were significantly better in EPO + EGF group than in all other groups Histopathological examination showed marked structural damage in control rats. The tubular damage was least in the EPO + EGF group. The control group had a significant increase in MDA level and a significant decrease in SOD and GSH, while the EPO + EGF group had a marked significant reduction in MDA and increase in GSH and SOD.
CONCLUSION
The protection against ischaemia/reperfusion injury might be maximal when EPO and EGF are administered concomitantly, and their protective effect might be partly due to their antioxidant effects.