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 journalArticle

244 Citations (Scopus)

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
StatePublished - Mar 15 1997

Fingerprint

Melanocyte-Stimulating Hormones
Ischemia
Kidney
Wounds and Injuries
Neutrophils
Nitric Oxide
Nitric Oxide Synthase Type II
Chemokines
Neutrophil Activation
Messenger RNA
Blood Urea Nitrogen
Intercellular Adhesion Molecule-1
Reperfusion Injury
Interleukin-8
Nitric Oxide Synthase
Transcriptional Activation
Reperfusion
Creatinine
Histology
Protein Isoforms

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Chiao, H., Kohda, Y., McLeroy, P., Craig, L., Housini, I., & Star, R. A. (1997). α-Melanocyte-stimulating hormone protects against renal injury after ischemia in mice and rats. Journal of Clinical Investigation, 99(6), 1165-1172.

α-Melanocyte-stimulating hormone protects against renal injury after ischemia in mice and rats. / Chiao, Hsi; Kohda, Yukimasa; McLeroy, Paul; Craig, Leonard; Housini, Ihsan; Star, Robert A.

In: Journal of Clinical Investigation, Vol. 99, No. 6, 15.03.1997, p. 1165-1172.

Research output: Contribution to journalArticle

Chiao, H, Kohda, Y, McLeroy, P, Craig, L, Housini, I & Star, RA 1997, 'α-Melanocyte-stimulating hormone protects against renal injury after ischemia in mice and rats', Journal of Clinical Investigation, vol. 99, no. 6, pp. 1165-1172.
Chiao, Hsi ; Kohda, Yukimasa ; McLeroy, Paul ; Craig, Leonard ; Housini, Ihsan ; Star, Robert A. / α-Melanocyte-stimulating hormone protects against renal injury after ischemia in mice and rats. In: Journal of Clinical Investigation. 1997 ; Vol. 99, No. 6. pp. 1165-1172.
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