α-Melanocyte-stimulating hormone protects against renal injury after ischemia in mice and rats

Hsi Chiao, Yukimasa Kohda, Paul McLeroy, Leonard Craig, Ihsan Housini, Robert A. Star

Research output: Contribution to journalArticlepeer-review

246 Scopus citations

Abstract

Reperfusion after ischemia induces cytokines, chemoattractaut chemokines, adhesion molecules, and nitric oxide (NO). The resultant neutrophil adherence and NO potentiates renal injury. α-Melanocyte- stimulating hormone (α-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 α-MSH inhibits renal injury in a model of bilateral renal ischemia. α-MSH significantly reduced ischemia-induced renal damage, measured by changes in renal histology and plasma blood urea nitrogen and creatinine in mice. α-MSH significantly decreased tubule necrosis, neutrophil plugging, and capillary congestion. Delay of α-MSH treatment for 6 h after ischemia also significantly inhibited renal damage. α-MSH also significantly inhibited ischemic damage in rats. To begin to determine the mechanism of action of α-MSH, we measured its effects on mediators of neutrophil trafficking and induction of the inducible isoform of NO synthase- II. α-MSH inhibited ischemia-induced increases in mRNA for the murine neutrophil chemokine KC/IL-8. α-MSH also inhibited induction of mRNA for the adhesion molecule ICAM-1, which is known to be critical in renal ischemic injury. α-MSH inhibited nitration of kidney proteins and induction of NO synthase-II. We conclude: (a) α-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.

Original languageEnglish (US)
Pages (from-to)1165-1172
Number of pages8
JournalJournal of Clinical Investigation
Volume99
Issue number6
DOIs
StatePublished - Mar 15 1997

Keywords

  • KC/IL-8
  • acute renal failure
  • inflammation
  • intracellular adhesion molecule-1
  • neutrophils
  • nitric oxide

ASJC Scopus subject areas

  • Medicine(all)

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