Protective effect of erythropoietin on renal ischemia and reperfusion injury.
BACKGROUND
Multiple protective effects of erythropoietin (EPO), such as antiapoptotic, antioxidant, angiogenic and neuroprotective effects, against ischemia have been demonstrated in cell culture and animal models. Genistein is also a potent tyrosine kinase inhibitor. The aims of the present study were to evaluate the effects of EPO on renal ischemia/reperfusion injury and to determine the role of the tyrosine kinase pathway on this process.


METHODS
Sprague-Dawley rats were assigned to five groups: (i) sham (Group I); (ii) control with renal ischemia (right nephrectomy and clamping on the left renal pedicle for 45 min and reperfusion; Group II); (iii) EPO + ischemia (Group III); (iv) genistein (an inhibitor of tyrosine kinase) + ischemia (Group IV); and (v) EPO + genistein + ischemia (Group V). Recombinant human EPO (1000 IU/kg) and genistein (10 mg/kg) were given 2 hours before ischemia. Blood samples and the left kidney were obtained after 45 min of reperfusion from half of the rats and after 24 h from the other half.


RESULTS
The blood urea nitrogen, creatinine, tumour necrosis factor-alpha (P < 0.05) and interleukin-2 (P < 0.01) levels, and renal tissue lipid peroxidation (P < 0.05) were significantly lower in Group III than in Group II at 45 min of reperfusion. Following 24 h of reperfusion, EPO decreased tissue peroxidation and histopathological injury, whereas genistein reversed it. The most prominent ischemic injury was observed in Group IV in which genistein was administered. There was no significant difference between Groups II and V.


CONCLUSIONS
These results suggest that EPO is effective in attenuating renal ischemia/reperfusion injury, and this effect may be related to tyrosine kinase activity.
Ates
Ersin
E
Department of General Surgery, Faculty of Medicine, Osmangazi University, Eskisehir, Turkey.
Yalcin
Ahmet Ugur
AU
Yilmaz
Sezgin
S
Koken
Tulay
T
Tokyol
Cigdem
C
D000818:Animals; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D004921:Erythropoietin / Q000627:therapeutic use*; D019833:Genistein / Q000627:therapeutic use; D007376:Interleukin-2 / Q000032:analysis; D007770:L-Lactate Dehydrogenase / Q000097:blood; D015227:Lipid Peroxidation; D008297:Male; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D004791:Enzyme Inhibitors; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin; D019833:Genistein; D007770:L-Lactate Dehydrogenase; D011505:Protein-Tyrosine Kinases