The role of nitric oxide in intestinal epithelial injury and restitution in neonatal necrotizing enterocolitis
Open accessAbstract
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.
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Elevated rates of generation of these oxidative inflammatory mediators can have direct effects on enterocytes and mucosal integrity, impair NO-dependent vascular function, reduce nitrate and nitrite absorption, and exert selective pressure on bacteria by augmenting innate anti-bacterial effects.
“Elevated rates of generation of these oxidative inflammatory mediators can have direct effects on enterocytes and mucosal integrity, impair NO-dependent vascular function, reduce nitrate and nitrite absorption, and exert selective pressure on bacteria by augmenting innate anti-bacterial effects[204,233,321–324].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [322]
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- Authors
- Chokshi, N. K., Guner, Y. S., Hunter, C. J., Upperman, J. S., Grishin, A., & Ford, H. R.
- Affiliations
- Children's Hospital Los Angeles (US)
- University of Southern California (US)
- Corresponding author
- Ford, Henri R.
- Venue
- Seminars in Perinatology
- Publisher
- Elsevier BV
- Published
- 2008-04
- Volume
- 32
- Issue
- 2
- Pages
- 92-99
- ISSN
- 0146-0005 (ISSN-L)
- PMC
- PMC2390779
- OpenAlex
- W2113663795
- Cited by
- 137
- References
- 87
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 4 · 2023: 12 · 2022: 7 · 2021: 7 · 2020: 5 · 2019: 8 · 2018: 7 · 2017: 10 · 2016: 6 · 2015: 11 · 2014: 7 · 2013: 9 · 2012: 12
- FWCI
- 0.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Seminars in Perinatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI049473)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Infant Nutrition and Health
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and fetal brain pathology
- Health Sciences › Health Professions › Speech and Hearing › Neonatal skin health care
- Keywords
- nitric oxide, necrotizing enterocolitis, intestinal epithelial damage, epithelial restitution, peroxynitrite, tight junctions, gap junctions, enterocyte apoptosis, enterocyte migration, enterocyte proliferation, preterm infants, intestinal ischemia, hypoxemia, bottle feeding
- MeSH terms
- Humans, Infant, Newborn, Infant, Premature, Intestinal Mucosa, Nitric Oxide, Permeability, Risk Factors, Apoptosis, Enterocolitis, Necrotizing, Enterocytes
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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