الفهرس 
Erythropoietin
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Abstract
Background: Erythropoietin (EPO), originally identified for its critical role in promoting erythrocyte survival and differentiation, has been shown to exert multiple paracrine/autocrine functions. Protective effects of EPO have been demonstrated in various tissues and experimental models of ischaemia-induced injury. Also EGF has been shown to exert mitogenic effects on various cell types. In the present study, we investigated the effect of EPO and EGF on in vivo rat model of renal ischaemia/ reperfusion (I/R) injury and the possible mechanisms of EPO and EGF actions in renal I/R injury. Methods: Male Sprague-Dwaley rats, subjected to renal ischaemia for 45 min, were administered either saline, EPO (5000 U/kg, i.v.), EGF (100 ug/kg, sc.), or combination of them 30 min prior to I/R. At 24, 48 h and 7days of reperfusion, the renal dysfunction and injury was assessed by measurement of serum and urine biochemical markers (creatinine clearance and FENa) and histological grading. Apoptosis was assessed by the morphological criteria in DNA fragmentation. Oxidative stress state was evaluated by measuring MDA, SOD and GSH. Expression of p53 and PCNA was also evaluated. Results: High levels of serum creatinine and FENa and low levels of creatinine clearance were identified at 24, 48 h and 7days after ischaemia. The EPO-treated group had significantly lower serum creatinine and FENa levels and increase creatinine clearance. The same was shown in EGF-treated group and EPO-EGF-treated groups. Semi-quantitative assessment of the histological lesions showed that rats subjected to I/R developed marked structural damage, whereas significantly less tubular damage was observed in the EPO, EGF and EPO-EGF-treated groups. I/R caused an increase in DNA fragmentation suggesting apoptosis. In the EPO, EGF, and EPO-EGF-treated rats low DNA fragmentation was observed. Also I/R caused an increase in MDA and significant decrease in SOD and GSH. Pretreatment with EPO, EGF and combination of both reduced significantly MDA and increased significantly SOD and GSH on 24 and 48 hours after ischaemia. Increased expression of p53 in the tubular epithelial cells was observed in the I/R-treated rats, while diminished expression of P53 was observed in the EPO and EPO-EGF-treated rats. Also a minimal expression of PCNA in the tubular epithelial cells was observed in the I/R-treated rats, while a great expression of PCNA was observed in the EPO-treated rats. Conclusion: Administration of EPO or EGF or combination of both before the onset of ischaemia produced a significant reduction in tubular injury, which was accompanied by a marked amelioration of renal functional impairment. The cytoprotective action of EPO and EGF against I/R injury seems to be associated with its anti-apoptotic action. Moreover, transcription factor P53 is likely to play a pivotal role in the pathophysiology of I/R renal injury might have a key role in EPO mediated protective effects. Also both agents have antioxidant effects. Also the protective effect of EPO and EGF might be due to its mitogenic action.