Carbon monoxide protects against the development of experimental necrotizing enterocolitis

Brian S. Zuckerbraun, Leo E. Otterbein, Patricia Boyle, Ronald Jaffe, Jeffrey Upperman, Ruben Zamora, Henri Ford

Research output: Contribution to journalArticle

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Abstract

Necrotizing enterocolitis (NEC) is a disease of neonates that is increasing in incidence and often results in significant morbidity and mortality. Carbon monoxide (CO), a byproduct of the catabolism of heme, is known to have anti-inflammatory and antiapoptotic properties. In this study, we aimed to demonstrate that inhaled CO protects against the development of intestinal inflammation in a model of experimental NEC as well as decreases enterocyte cell death in vitro. Additionally, we also aimed to demonstrate that CO decreases enterocyte production of inducible nitric oxide synthase (iNOS) and nitric oxide (NO). Neonatal rats were exposed to intermittent hypoxia exposure and formula feeding to induce experimental NEC. Animals randomized to CO treatment were put in an environment containing 0.025% CO for 1 h/day on days 1-3 of life. All animals were killed on day 4 of life. In vitro experiments were performed with IEC-6 cells, a rat enterocyte cell line. Cells were examined for viability, iNOS production, and elaboration of NO. We found that CO diminished levels of serum inflammatory cytokines and nitrites, protected against intestinal inflammation, and decreased ileal iNOS production and protein nitration in a model of experimental NEC. In vitro, CO decreased cytokine- or hypoxia/endotoxin-induced iNOS and NO production. CO also abrogated TNF-α- and actinomycin D-induced apoptosis or hypoxia/endotoxin-induced cell death. In conclusion, 1 h of daily low-dose inhaled CO protected against the development of intestinal inflammation in a model of experimental NEC. iNOS and NO production were decreased by CO both in vivo and in vitro. CO may prove to be a useful clinical adjunct in the treatment of NEC.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume289
Issue number3 52-3
DOIs
StatePublished - Sep 1 2005
Externally publishedYes

Fingerprint

Necrotizing Enterocolitis
Carbon Monoxide
Nitric Oxide Synthase Type II
Enterocytes
Nitric Oxide
Theoretical Models
Inflammation
Endotoxins
Cell Death
Cytokines
Dactinomycin
Nitrites
Heme
Anti-Inflammatory Agents
Apoptosis

Keywords

  • Heme oxygenase
  • Nitric oxide

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

Carbon monoxide protects against the development of experimental necrotizing enterocolitis. / Zuckerbraun, Brian S.; Otterbein, Leo E.; Boyle, Patricia; Jaffe, Ronald; Upperman, Jeffrey; Zamora, Ruben; Ford, Henri.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 289, No. 3 52-3, 01.09.2005.

Research output: Contribution to journalArticle

Zuckerbraun, Brian S. ; Otterbein, Leo E. ; Boyle, Patricia ; Jaffe, Ronald ; Upperman, Jeffrey ; Zamora, Ruben ; Ford, Henri. / Carbon monoxide protects against the development of experimental necrotizing enterocolitis. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2005 ; Vol. 289, No. 3 52-3.
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