Inhaled carbon monoxide suppresses the development of postoperative ileus in the murine small intestine. Academic Article uri icon

Overview

MeSH

  • Administration, Inhalation
  • Animals
  • Anti-Inflammatory Agents
  • Cyclooxygenase 2
  • Cytokines
  • Gene Expression
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Histocytochemistry
  • Inflammation Mediators
  • Interleukin-10
  • Isoenzymes
  • Male
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Peroxidase
  • Postoperative Complications
  • Prostaglandin-Endoperoxide Synthases

MeSH Major

  • Abdomen
  • Carbon Monoxide
  • Intestinal Obstruction
  • Intestine, Small

abstract

  • The induction of heme oxygenase (HO-1), the rate-limiting enzyme in heme metabolism, is protective against injury in acute and chronic inflammation. Inhalation of low levels of carbon monoxide (CO), a byproduct of heme metabolism, has anti-inflammatory effects equal to HO-1 induction. This study examined whether inhaled CO was protective against the development of postoperative ileus. Ileus was induced by surgical anesthesia and gentle manipulation of the mouse small intestine. Animals were exposed to CO (250 ppm) in air 1 hour before and continuously for 24 hours after surgery. CO inhalation prevented the manipulation-induced suppression of circular muscle contractility in vitro, and significantly improved gastrointestinal transit in vivo. Proinflammatory messenger RNA (mRNA) expression (interleukin [IL]-6, IL-1beta, cyclooxygenase 2 [COX-2], inducible nitric oxide [iNOS]) and anti-inflammatory mediator expression (IL-10 and HO-1) were elevated 3 to 6 hours after surgery relative to controls. CO treatment reduced IL-1beta and iNOS peak expression by 75%, but not IL-6 or COX-2. In manipulated mice treated with CO, HO-1 expression peaked earlier (3 hours after surgery) and at levels 300% higher than in mice not exposed to CO. IL-10 expression at 3 hours also was 300% higher after CO treatment. These findings suggest that CO attenuates postoperative ileus by inhibiting selective elements within the inflammatory cascade and by enhanced induction of the anti-inflammatory cytokine IL-10. In addition, the early and enhanced induction of HO-1 potentially amplifies the anti-inflammatory effects of the HO-1 pathway by protection from free radical stress and by increasing the tissue availability of CO directly at the sites of inflammation.

publication date

  • February 2003

has subject area

  • Abdomen
  • Administration, Inhalation
  • Animals
  • Anti-Inflammatory Agents
  • Carbon Monoxide
  • Cyclooxygenase 2
  • Cytokines
  • Gene Expression
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Histocytochemistry
  • Inflammation Mediators
  • Interleukin-10
  • Intestinal Obstruction
  • Intestine, Small
  • Isoenzymes
  • Male
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Peroxidase
  • Postoperative Complications
  • Prostaglandin-Endoperoxide Synthases

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1053/gast.2003.50060

PubMed ID

  • 12557144

Additional Document Info

start page

  • 377

end page

  • 391

volume

  • 124

number

  • 2