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

Nephron Physiol. 2007;105(4):p57-65. doi: 10.1159/000100425. Epub 2007 Mar 1.

Abstract

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.

MeSH terms

  • Alprostadil / pharmacology*
  • Animals
  • Arginine / pharmacology*
  • Creatinine / blood
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Kidney / drug effects
  • Kidney / pathology
  • Kidney / physiology
  • Kidney Diseases / drug therapy*
  • Kidney Diseases / pathology
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / pathology
  • Sodium / urine
  • Survival Analysis
  • Urine
  • Vasodilator Agents / pharmacology*

Substances

  • Vasodilator Agents
  • Arginine
  • Sodium
  • Creatinine
  • Alprostadil