Heme oxygenase-1 upregulation protects against intestinal ischemia/reperfusion injury: A laboratory based study

Nir Wasserberg, Antonello Pileggi, Shashikumar K. Salgar, Phillip Ruiz, Camillo Ricordi, Luca A Inverardi, Andreas G. Tzakis

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Objectives: Tissue damage caused by ischemia/reperfusion injury (IRI) of the intestine may lead to organ dysfunction in several clinical conditions, and is associated with increased incidence of chronic rejection after transplantation. Heme oxygenase-1 (HO-1) is a stress-inducible protein capable of modulating inflammation, oxidative stress, and cell death. The aim of the present study was to assess the effects of HO-1 upregulation on intestinal IRI. Methods: Lewis rats (seven groups, n = 6 each) underwent intestinal warm ischemia induced by clamping the superior mesenteric artery and by ligating the inferior mesenteric artery for 60 min. After 120 or 240 min of reperfusion, tissue samples were collected for analysis. Cobalt protoporphyrin (CoPP) was administered IP at 10 or 20 mg/kg 24 h before IRI, to induce HO-1 upregulation. Control animals received vehicle alone. Tissue injury measurements included the following: histological changes, tissue myeloperoxidase (MPO) activity, nitrate/nitrite levels, and IL-6 levels. Results: A significant HO-1 upregulation was demonstrated in pre-treated animals (p < 0.05, 95% CI: -0.84 to -0.05). Intestinal IL-6 mRNA expression levels were significantly reduced in animals treated with CoPP 20 mg/kg after 240 min of IRI (p < 0.05, 95% CI: 0.09-2.25). Significant reduction in MPO activity and NO products was observed in treated animals when compared to controls (p < 0.01, 95% CI: 0.07-0.24 and p < 0.01, 95% CI: 5.58-12.75, respectively). Conclusions: Induction of HO-1 by CoPP administration before IRI was resulted in a significant reduction of intestinal tissue injury. Developing strategies to induce HO-1 upregulation before surgery will be important to reduce IRI in the clinical setting.

Original languageEnglish
Pages (from-to)216-224
Number of pages9
JournalInternational Journal of Surgery
Volume5
Issue number4
DOIs
StatePublished - Aug 1 2007

Fingerprint

Heme Oxygenase-1
Reperfusion Injury
Up-Regulation
Peroxidase
Interleukin-6
Inferior Mesenteric Artery
Warm Ischemia
Superior Mesenteric Artery
Wounds and Injuries
Graft Rejection
Nitrites
Heat-Shock Proteins
Constriction
Nitrates
Reperfusion
Intestines
Oxidative Stress
Cell Death
Inflammation
Messenger RNA

Keywords

  • Heme oxygenase-1
  • Intestine
  • Ischemia/reperfusion injury

ASJC Scopus subject areas

  • Surgery

Cite this

Heme oxygenase-1 upregulation protects against intestinal ischemia/reperfusion injury : A laboratory based study. / Wasserberg, Nir; Pileggi, Antonello; Salgar, Shashikumar K.; Ruiz, Phillip; Ricordi, Camillo; Inverardi, Luca A; Tzakis, Andreas G.

In: International Journal of Surgery, Vol. 5, No. 4, 01.08.2007, p. 216-224.

Research output: Contribution to journalArticle

Wasserberg, Nir ; Pileggi, Antonello ; Salgar, Shashikumar K. ; Ruiz, Phillip ; Ricordi, Camillo ; Inverardi, Luca A ; Tzakis, Andreas G. / Heme oxygenase-1 upregulation protects against intestinal ischemia/reperfusion injury : A laboratory based study. In: International Journal of Surgery. 2007 ; Vol. 5, No. 4. pp. 216-224.
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AU - Pileggi, Antonello

AU - Salgar, Shashikumar K.

AU - Ruiz, Phillip

AU - Ricordi, Camillo

AU - Inverardi, Luca A

AU - Tzakis, Andreas G.

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