Mechanisms of nitric oxide-mediated intestinal barrier failure in necrotizing enterocolitis

Jeffrey S. Upperman, Douglas Potoka, Anatoly Grishin, David Hackam, Ruben Zamora, Henri R. Ford

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


Necrotizing enterocolitis (NEC) is the leading intestinal emergency in premature infants. The underlying etiology of NEC remains elusive, but hypoxic conditions and early enteral feeding are consistently implicated as the main risk factors in the pathogenesis of NEC. We postulate that nitric oxide (NO) plays a key role as a molecular signaling "hub" in the generation of gut barrier failure in NEC. Clinical studies suggest that inflammatory cytokines and excessive NO production may contribute to the pathogenesis of NEC. One of the major challenges in defining the critical signaling pathways that lead to the development of NEC is the lack of specific biochemical markers that consistently delineate the early stages of NEC. Intestinal pathology and molecular markers derived from late-stage NEC represent end-stage findings and thus provide little insight into the early events that led to intestinal inflammation. Such markers may not represent viable therapeutic targets for the treatment or prevention of NEC. Therefore, novel strategies are needed to identify the patients at risk for NEC and define the clinically relevant molecules that characterize the early stages of NEC. This review will examine the mechanisms of NO-mediated gut barrier failure and propose novel genetic-based approaches for elucidating the critical molecular pathways in NEC.

Original languageEnglish (US)
Pages (from-to)159-166
Number of pages8
JournalSeminars in pediatric surgery
Issue number3
StatePublished - Aug 2005
Externally publishedYes


  • Gene polymorphism
  • Intestinal inflammation
  • Micro array
  • Necrotizing enterocolitis
  • Nitric oxide
  • Sepsis

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Surgery


Dive into the research topics of 'Mechanisms of nitric oxide-mediated intestinal barrier failure in necrotizing enterocolitis'. Together they form a unique fingerprint.

Cite this