Alpha-melanocyte-stimulating hormone protects against renal injury after ischemia in mice and rats

J Clin Invest. 1997 Mar 15;99(6):1165-72. doi: 10.1172/JCI119272.


Reperfusion after ischemia induces cytokines, chemoattractant chemokines, adhesion molecules, and nitric oxide (NO). The resultant neutrophil adherence and NO potentiates renal injury. alpha-Melanocyte-stimulating hormone (alpha-MSH) is a potent anti-inflammatory agent that inhibits neutrophil migration and production of neutrophil chemokines and NO. Since neutrophils and NO promote renal ischemic injury, we sought to determine if alpha-MSH inhibits renal injury in a model of bilateral renal ischemia. alpha-MSH significantly reduced ischemia-induced renal damage, measured by changes in renal histology and plasma blood urea nitrogen and creatinine in mice. alpha-MSH significantly decreased tubule necrosis, neutrophil plugging, and capillary congestion. Delay of alpha-MSH treatment for 6 h after ischemia also significantly inhibited renal damage. alpha-MSH also significantly inhibited ischemic damage in rats. To begin to determine the mechanism of action of alpha-MSH, we measured its effects on mediators of neutrophil trafficking and induction of the inducible isoform of NO synthase-II. alpha-MSH inhibited ischemia-induced increases in mRNA for the murine neutrophil chemokine KC/IL-8. alpha-MSH also inhibited induction of mRNA for the adhesion molecule ICAM-1, which is known to be critical in renal ischemic injury. alpha-MSH inhibited nitration of kidney proteins and induction of NO synthase-II. We conclude: (a) alpha-MSH protects against renal ischemia/reperfusion injury; and (b) it may act, in part, by inhibiting the maladaptive activation of genes that cause neutrophil activation and adhesion, and induction of NO synthase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Northern
  • Cell Adhesion Molecules / genetics
  • Chemokines / genetics
  • Drug Administration Schedule
  • Female
  • Kidney / blood supply*
  • Kidney / drug effects
  • Kidney / pathology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Nitrates / metabolism
  • Nitric Oxide Synthase / biosynthesis
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology*
  • alpha-MSH / administration & dosage
  • alpha-MSH / pharmacology*


  • Cell Adhesion Molecules
  • Chemokines
  • Nitrates
  • RNA, Messenger
  • alpha-MSH
  • Nitric Oxide Synthase