Alpha-melanocyte-stimulating hormone protects against mesenteric ischemia-reperfusion injury

• Published in: American journal of physiology: Gastrointestinal and liver physiology Vol. 282; no. 6; pp. G1059 - G1068
• Main Authors: Hassoun, Heitham T, Zou, Lei, Moore, Frederick A, Kozar, Rosemary A, Weisbrodt, Norman W, Kone, Bruce C
• Format: Journal Article
• Language: English
• Published: United States 01.06.2002
• Subjects: alpha-MSH - pharmacology; Animals; Gastrointestinal Motility; Intestinal Mucosa - metabolism; Intestinal Obstruction - drug therapy; Intestinal Obstruction - prevention & control; Intestine, Small - blood supply; Intestine, Small - physiology; Male; NF-kappa B - metabolism; Peptides - metabolism; Rats; Rats, Sprague-Dawley; Reperfusion Injury - drug therapy; Splanchnic Circulation
• ISSN: 0193-1857; 1522-1547
• DOI: 10.1152/ajpgi.00073.2001

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-kappaB (NF-kappaB) activation after 45 min of superior mesenteric artery occlusion and <or=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-kappaB 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-kappaB and myeloperoxidase activity after prolonged (6 h) reperfusion. We conclude that alpha-MSH significantly limits postischemic injury to the rat small intestine.