Alpha-melanocyte-stimulating hormone protects against mesenteric ischemia-reperfusion injury.
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.
Hassoun
Heitham T
HT
Department of Surgery, University of Texas Medical School at Houston, Houston, Texas 77030, USA.
Zou
Lei
L
Moore
Frederick A
FA
Kozar
Rosemary A
RA
Weisbrodt
Norman W
NW
Kone
Bruce C
BC
D000818:Animals; D005769:Gastrointestinal Motility; D007413:Intestinal Mucosa / Q000378:metabolism; D007415:Intestinal Obstruction / Q000188:drug therapy / Q000517:prevention & control; D007421:Intestine, Small / Q000098:blood supply / Q000502:physiology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*; D013152:Splanchnic Circulation; D000521:alpha-MSH / Q000494:pharmacology*
D016328:NF-kappa B; D010455:Peptides; C118258:SN50 peptide; D000521:alpha-MSH