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Am J Physiol Gastrointest Liver Physiol 282: G1059-G1068, 2002. First published March 13, 2002; doi:10.1152/ajpgi.00073.2001
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Vol. 282, Issue 6, G1059-G1068, June 2002

alpha -Melanocyte-stimulating hormone protects against mesenteric ischemia-reperfusion injury

Heitham T. Hassoun1,4, Lei Zou2,4, Frederick A. Moore1,4, Rosemary A. Kozar1,4, Norman W. Weisbrodt3,4, and Bruce C. Kone2,3,4

Departments of 1 Surgery, 2 Internal Medicine, and 3 Integrative Biology and Pharmacology, and 4 Trauma Research Center, University of Texas Medical School at Houston, Houston, Texas 77030

Mesenteric ischemia-reperfusion (I/R) injury to the intestine is a common and often devastating clinical occurrence for which there are few therapeutic options. alpha -Melanocyte-stimulating hormone (alpha -MSH) is a tridecapeptide released by the pituitary gland and immunocompetent cells that exerts anti-inflammatory actions and abrogates postischemic injury to the kidneys and brainstem of rodents. To test the hypothesis that alpha -MSH would afford similar protection in the postischemic small intestine, we analyzed the effects of this peptide on intestinal transit, histology, myeloperoxidase activity, and nuclear factor-kappa B (NF-kappa B) activation after 45 min of superior mesenteric artery occlusion and <= 6 h of reperfusion. Rats subjected to I/R exhibited markedly depressed intestinal transit, histological evidence of severe injury to the ileum, increased myeloperoxidase activity in ileal cytoplasmic extracts, and biphasic activation of NF-kappa B in ileal nuclear extracts. In contrast, rats treated with alpha -MSH before I/R exhibited intestinal transit and histological injury scores comparable to those of sham-operated controls. In addition, the alpha -MSH-treated rats demonstrated less I/R-induced activation of intestinal NF-kappa B and myeloperoxidase activity after prolonged (6 h) reperfusion. We conclude that alpha -MSH significantly limits postischemic injury to the rat small intestine.

transcription factor; nuclear factor-kappa B; ileus; small intestine


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