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

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.

Role of combined L-arginine and prostaglandin E1 in renal ischemia-reperfusion injury.

BACKGROUND: L-Arginine (L-arg) and Prostaglandin E(1) (PGE(1)) have been used effectively as single agents to ameliorate renal ischemia-reperfusion injury. We hypothesized that combined treatment with L-arg and PGE(1 )would be more effective. MATERIALS AND METHODS: The left renal artery of male Sprague-Dawley rats was clamped for 45 min and the right kidney was removed. Fifty six rats were randomly allocated into 5 groups each consisted of 12 rats except sham group (n = 8). (1) sham, underwent right nephrectomy only; (2) control, untreated ischemic rats; (3) L-arg group, L-arg-treated ischemic rats; (4) PGE(1) group, PGE(1)-treated ischemic rats; (5) L-arg+PGE(1) group, ischemic rats treated with both L-arg and PGE(1). Renal function and histology were assessed on days 2 and 7 postoperatively. RESULTS: All rats, except control ones, showed a significant improvement of renal function towards normal on postoperative day 7. Serum creatinine and creatinine clearance were significantly better in L-arg+PGE(1) group compared to all other groups on day 7. With the exception of sham-operated and L-arg+PGE(1)-treated animals, all other groups showed significant increases in fractional excretion of sodium (FE(Na)) in response to renal ischemia-reperfusion. The severest tubular damage was determined in the kidneys of control rats. Rats treated with L-arg+PGE(1) had the least severe tubular damage. CONCLUSION: The administration of either L-arg or PGE(1) attenuates both functional and structural consequences of renal warm ischemia. A near total protection might be achieved when both agents are administered concomitantly.