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Articles in PresS, published online ahead of print March 13, 2002
Am J Physiol Gastrointest Liver Physiol, 10.1152/ajpgi.00073.2001
Submitted on February 20, 2001
Accepted on January 24, 2002
-Melanocyte Stimulating Hormone Protects Against Mesenteric Ischemia/Reperfusion Injury
1 Department of Surgery, The University of Texas Medical School at Houston, Houston, TX, USA
2 Department of Internal Medicine, The University of Texas Medical School at Houston, Houston, TX, USA
3 Department of Integrative Biology and Pharmacology and The Trauma Research Center, The University of Texas Medical School at Houston, Houston, TX, USA
4 Department of Internal Medicine, The University of Texas Medical School at Houston, Houston, TX, USA; Department of Integrative Biology and Pharmacology and The Trauma Research Center, The University of Texas Medical School at Houston, Houston, TX, USA
* To whom correspondence should be addressed. E-mail: Bruce.C.Kone{at}uth.tmc.edu.
Mesenteric ischemia/reperfusion (I/R) injury to the intestine is a common and often devastating clinical occurrence for which there are few therapeutic options. -Melanocyte-stimulating hormone (-MSH) is a tridecapeptide released by the pituitary gland and immunocompetent cells that exerts anti-inflammatory actions and abrogates post-ischemic injury to the kidneys and brainstem of rodents. To test the hypothesis that -MSH would afford similar protection in the post-ischemic small intestine, we analyzed the effects of this peptide on intestinal transit, histology, myeloperoxidase activity, and NF-
B activation following 45 min of superior mesenteric artery occlusion and up to 6 hours of reperfusion. Rats subjected to I/R exhibited markedly depressed intestinal transit, histologic evidence of severe injury to the ileum, increased myeloperoxidase activity in ileal cytoplasmic extracts, and biphasic activation of NF-B in ileal nuclear extracts. In contrast, rats treated with -MSH before I/R exhibited intestinal transit and histologic injury scores comparable to those of sham-operated controls. In addition, the -MSH-treated rats demonstrated less I/R-induced activation of intestinal NF-B and myeloperoxidase activity after prolonged (6 hours) reperfusion. We conclude that -MSH significantly limits post-ischemic injury to the rat small intestine.
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