The Role of Nitric Oxide in Intestinal Epithelial Injury and Restitution in Neonatal Necrotizing Enterocolitis

Nikunj K. Chokshi, Yigit S. Guner, Catherine J. Hunter, Jeffrey S. Upperman, Anatoly Grishin, Henri R. Ford*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

93 Scopus citations


Necrotizing enterocolitis (NEC) is the most common life-threatening gastrointestinal disease encountered in the premature infant. Although the inciting events leading to NEC remain elusive, various risk factors, including prematurity, hypoxemia, formula feeding, and intestinal ischemia, have been implicated in the pathogenesis of NEC. Data from our laboratory and others suggest that NEC evolves from disruption of the intestinal epithelial barrier, as a result of a combination of local and systemic insults. We postulate that nitric oxide (NO), an important second messenger and inflammatory mediator, plays a key role in intestinal barrier failure seen in NEC. Nitric oxide and its reactive nitrogen derivative, peroxynitrite, may affect gut barrier permeability by inducing enterocyte apoptosis (programmed cell death) and necrosis, or by altering tight junctions or gap junctions that normally play a key role in maintaining epithelial monolayer integrity. Intrinsic mechanisms that serve to restore monolayer integrity following epithelial injury include enterocyte proliferation, epithelial restitution via enterocyte migration, and re-establishment of cell contacts. This review focuses on the biology of NO and the mechanisms by which it promotes epithelial injury while concurrently disrupting the intrinsic repair mechanisms.

Original languageEnglish (US)
Pages (from-to)92-99
Number of pages8
JournalSeminars in Perinatology
Issue number2
StatePublished - Apr 2008


  • intestinal inflammation
  • intestinal restitution
  • necrotizing enterocolitis
  • nitric oxide

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Obstetrics and Gynecology


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