Role of Combined L-Arginine and Prostaglandin E₁ in Renal Ischemia-Reperfusion Injury

Abstract

Background:L-Arginine (L-arg) and Prostaglandin E₁ (PGE₁) have been used effectively as single agents to ameliorate renal ischemia-reperfusion injury. We hypothesized that combined treatment with L-arg and PGE₁would 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) PGE₁ group, PGE₁-treated ischemic rats; (5) L-arg+PGE₁ group, ischemic rats treated with both L-arg and PGE₁. 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+PGE₁ group compared to all other groups on day 7. With the exception of sham-operated and L-arg+PGE₁-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+PGE₁ had the least severe tubular damage. Conclusion: The administration of either L-arg or PGE₁ attenuates both functional and structural consequences of renal warm ischemia. A near total protection might be achieved when both agents are administered concomitantly.

Pre-conditioned mesenchymal stem cells ameliorate renal ischemic injury in rats by augmented survival and engraftment

“…Inflammatory process and primary ischemic injury in vascular cells results in prolonged localized ischemia that substantially increases severity of injury in affected areas. During ischemia, the endothelium produces free radicals and secretes chemo-attractants which upon reperfusion sequester and activate neutrophils and intensification of the injury [1]. AKI associated mortality is estimated as 50% in hospitalized patients and 70-80% in patients under intensive care [2,3].…”

“…It protects macrophages, hepatocytes, cardiomyocytes against different injuries by modifying expression of different genes [14]. Various donors of NO have been implicated as cyto-protective and tissue protective factors in vivo [1,15]. …”

Role of combination of l‐arginine and α‐tocopherol in renal transplantation ischaemia/reperfusion injury: a randomized controlled experimental study in a rat model

“…[26] and Mahmoud et al . [27] who stated that acute post‐ischaemic renal failure may be alleviated by administrating the NO substrate ( l ‐arginine). Sun et al .…”

Effect of the technique for assisting renal blood circulation on ischemic kidney in acute cardiorenal syndrome

“…Delivery of therapeutic agents directly to the kidneys has the advantage of providing a higher local effective dose with potentially greater renal effects, while limiting systemic exposure and adverse effects because of renal first-pass elimination. The rationale for using PGE 1 included its properties as a potent vasodilator and its reported benefit in preventing renal ischemia under hypoperfusion and ischemia [14,15]. The rate of 0.015 lg/kg/min of PGE 1 for a kidney was arbitrarily determined based on data showing that low systemic infusion rates of PGE 1 below 0.032 lg/kg/min do not cause a change in blood pressure or heart rate in healthy humans [16,17].…”