A somatostatin analogue, octreotide, ameliorates intestinal ischemia-reperfusion injury through the early induction of heme oxygenase-1

Takeshi Takano, Yoshikazu Yonemitsu, Satoru Saito, Hiroyuki Itoh, Toshihiro Onohara, Atsushi Fukuda, Maki Takai, Yoshihiko Maehara

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)350-358
Number of pages9
JournalJournal of Surgical Research
Volume175
Issue number2
DOIs
Publication statusPublished - Jun 15 2012

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Heme Oxygenase-1
Octreotide
Somatostatin
Reperfusion Injury
Superior Mesenteric Artery
Ischemia
Free Radical Scavengers
Therapeutic Uses
Surgical Instruments
Small Intestine
Intestines
Sprague Dawley Rats
Cell Count
Western Blotting
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Survival
Mortality
phenylmethylpyrazolone
Proteins

All Science Journal Classification (ASJC) codes

  • Surgery

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A somatostatin analogue, octreotide, ameliorates intestinal ischemia-reperfusion injury through the early induction of heme oxygenase-1. / Takano, Takeshi; Yonemitsu, Yoshikazu; Saito, Satoru; Itoh, Hiroyuki; Onohara, Toshihiro; Fukuda, Atsushi; Takai, Maki; Maehara, Yoshihiko.

In: Journal of Surgical Research, Vol. 175, No. 2, 15.06.2012, p. 350-358.

Research output: Contribution to journalArticle

Takano, Takeshi ; Yonemitsu, Yoshikazu ; Saito, Satoru ; Itoh, Hiroyuki ; Onohara, Toshihiro ; Fukuda, Atsushi ; Takai, Maki ; Maehara, Yoshihiko. / A somatostatin analogue, octreotide, ameliorates intestinal ischemia-reperfusion injury through the early induction of heme oxygenase-1. In: Journal of Surgical Research. 2012 ; Vol. 175, No. 2. pp. 350-358.
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AU - Takano, Takeshi

AU - Yonemitsu, Yoshikazu

AU - Saito, Satoru

AU - Itoh, Hiroyuki

AU - Onohara, Toshihiro

AU - Fukuda, Atsushi

AU - Takai, Maki

AU - Maehara, Yoshihiko

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AB - 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.

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