title: A somatostatin analogue, octreotide, ameliorates intestinal ischemia-reperfusion injury through the early induction of heme oxygenase-1.
abstract: BACKGROUND
  Intestinal damage after ischemia followed by revascularization, referred to as "ischemia-reperfusion (I/R) injury," is a devastating complication that can occur after acute superior mesenteric obstruction, or after both elective and emergent abdominal aortic surgery. Once an entire layer of intestine is involved in severe ischemia, the mortality rate reaches 90%; no effective medical treatment has been reported to date. Here, we demonstrate that a somatostatin analogue, octreotide, but not a free-radical scavenger, MCI-186, prevented death due to surgically induced intestinal I/R injury in rats.
  
  
  METHODS
  Superior mesenteric artery (SMA) of Male Sprague-Dawley rats, that received MCI-186 or octreotide, was surgically clamped, and then the clips were removed and SMA blood flow restored. Survival was assessed, and blood and small intestine were subjected to cell count, enzyme-linked immunosorbent assay (ELISA), Western blotting, and immunohistochemistry.
  
  
  RESULTS
  Of interest, pretreatment with octreotide, but not with MCI-186, just before induced intestinal ischemia prompted the early expression of heme oxygenase-1 (HO-1) protein-associated accumulation of CD68-positive cells, a possible cellular source of HO-1. Inversely, the administration of tin protoporphyrin IX (SnPPN), a specific inhibitor of HO-1, completely abolished the therapeutic effects of octreotide, indicating that the favorable effects of octreotide against intestinal I/R injury is predominantly dependent on the early induction of HO-1.
  
  
  CONCLUSIONS
  These results suggest that a somatostatin analogue may be useful in leading to an improvement of the prognosis of patients with intestinal I/R injury in the clinical setting.
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Takano
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Yonemitsu
authors.forename: Satoru
authors.initials: S
authors.lastname: Saito
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Itoh
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Onohara
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fukuda
authors.forename: Maki
authors.initials: M
authors.lastname: Takai
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077553:Edaravone; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000627:therapeutic use; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007420:Intestine, Large / Q000098:blood supply* / Q000378:metabolism*; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology; D023421:Models, Animal; D015282:Octreotide / Q000627:therapeutic use*; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000502:physiology; D015427:Reperfusion Injury / Q000517:prevention & control*; D013004:Somatostatin / Q000031:analogs & derivatives*
chemical_list: D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D008665:Metalloporphyrins; D011524:Protoporphyrins; D013004:Somatostatin; C032628:tin protoporphyrin IX; D051547:Heme Oxygenase-1; D015282:Octreotide; D000077553:Edaravone; D000983:Antipyrine