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

H Chiao, Y Kohda, P McLeroy, L Craig, I Housini, R A Star, H Chiao, Y Kohda, P McLeroy, L Craig, I Housini, R A Star

Abstract

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.

References

    1. Transplantation. 1995 Apr 15;59(7):962-8
    1. Ann N Y Acad Sci. 1994 Nov 25;741:137-48
    1. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):8016-20
    1. Neuroimmunomodulation. 1994 Jan;1(1):28-32
    1. J Leukoc Biol. 1996 Feb;59(2):248-53
    1. J Clin Invest. 1996 Feb 15;97(4):1056-63
    1. J Clin Invest. 1996 May 1;97(9):2038-44
    1. J Clin Invest. 1996 May 15;97(10):2377-83
    1. N Engl J Med. 1996 May 30;334(22):1448-60
    1. Br J Surg. 1996 Feb;83(2):162-70
    1. Am J Physiol. 1996 Jun;270(6 Pt 2):F971-7
    1. Peptides. 1996;17(4):675-9
    1. Psychopharmacology (Berl). 1977 Dec 19;55(2):165-72
    1. Pharmacol Biochem Behav. 1978 Aug;9(2):207-12
    1. Anal Biochem. 1987 Apr;162(1):156-9
    1. Am J Physiol. 1989 May;256(5 Pt 2):F794-802
    1. Kidney Int. 1989 Oct;36(4):555-61
    1. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6368-71
    1. Am J Physiol. 1991 Dec;261(6 Pt 2):F1095-101
    1. Science. 1992 Aug 28;257(5074):1248-51
    1. Virchows Arch B Cell Pathol Incl Mol Pathol. 1992;62(4):237-43
    1. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11876-80
    1. Endocr Rev. 1993 Oct;14(5):564-76
    1. Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):812-6
    1. Am J Physiol. 1994 Jan;266(1 Pt 2):F129-34
    1. Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1691-5
    1. Biol Chem Hoppe Seyler. 1994 Feb;375(2):81-8
    1. Am J Physiol. 1994 Jun;266(6 Pt 2):F949-56
    1. N Engl J Med. 1994 Nov 17;331(20):1338-42
    1. Biochem Biophys Res Commun. 1995 Jun 6;211(1):67-73

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner