Epidermal growth factor reduces hepatic sequelae in experimental necrotizing enterocolitis

Melissa D Halpern, Hana Holubec, Jessica A. Clark, Tara A. Saunders, Catherine S. Williams, Katerina Dvorak, Bohuslav Dvorak

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background and Aim: Neonatal necrotizing enterocolitis (NEC) is the most common gastrointestinal disease of premature infants. We recently demonstrated that the gut/liver axis plays an important role in the pathophysiology of NEC through the release of inflammatory mediators into the intestinal lumen. We have also shown that supplementation of formula with epidermal growth factor (EGF) dramatically decreases ileal pathology associated with experimental NEC. In this study, we examined the effects of EGF on the liver portion of the gut/liver axis in the neonatal rat model of NEC. Methods: Newborn rats were divided into three experimental groups, NEC, hand-fed with growth-factor free formula; NEC + EGF, hand-fed with formula supplemented with 500 ng/ml rat EGF; or DF, dam fed. All animals were exposed to asphyxia and cold stress twice daily for 4 days to develop NEC. Results: EGF receptor expression was significantly (p ≤ 0.01) decreased in the NEC + EGF group compared to the NEC group. EGF supplementation significantly decreased Kupffer cell numbers (p ≤ 0.01) as well as hepatic tumor necrosis factor (TNF)-α and interleukin-18 production (p ≤ 0.05). Further, TNF-α in the intestinal luminal contents of the NEC + EGF group were normalized to levels observed in DF controls compared to the NEC group (p ≤ 0.05). Activated nuclear factor-κB was also substantially decreased in the NEC + EGF group versus the NEC group. Conclusion: The results of this study indicate that EGF normalizes cytokine overproduction in the liver of neonatal rats with NEC, which contributes to diminished intestinal damage during the development of experimental NEC. These data suggest that supplementation of formula with EGF can have beneficial effects on the gut/liver axis during NEC pathogenesis.

Original languageEnglish (US)
Pages (from-to)227-235
Number of pages9
JournalBiology of the Neonate
Volume89
Issue number4
DOIs
StatePublished - Jun 2006

Fingerprint

Necrotizing Enterocolitis
Epidermal Growth Factor
Liver
Hand
Tumor Necrosis Factor-alpha
Gastrointestinal Contents
Interleukin-18
Kupffer Cells
Gastrointestinal Diseases
Asphyxia

Keywords

  • Cytokines
  • Epidermal growth factor
  • Gut/liver axis
  • Necrotizing enterocolitis

ASJC Scopus subject areas

  • Developmental Biology
  • Pediatrics, Perinatology, and Child Health

Cite this

Halpern, M. D., Holubec, H., Clark, J. A., Saunders, T. A., Williams, C. S., Dvorak, K., & Dvorak, B. (2006). Epidermal growth factor reduces hepatic sequelae in experimental necrotizing enterocolitis. Biology of the Neonate, 89(4), 227-235. https://doi.org/10.1159/000090015

Epidermal growth factor reduces hepatic sequelae in experimental necrotizing enterocolitis. / Halpern, Melissa D; Holubec, Hana; Clark, Jessica A.; Saunders, Tara A.; Williams, Catherine S.; Dvorak, Katerina; Dvorak, Bohuslav.

In: Biology of the Neonate, Vol. 89, No. 4, 06.2006, p. 227-235.

Research output: Contribution to journalArticle

Halpern, MD, Holubec, H, Clark, JA, Saunders, TA, Williams, CS, Dvorak, K & Dvorak, B 2006, 'Epidermal growth factor reduces hepatic sequelae in experimental necrotizing enterocolitis', Biology of the Neonate, vol. 89, no. 4, pp. 227-235. https://doi.org/10.1159/000090015
Halpern, Melissa D ; Holubec, Hana ; Clark, Jessica A. ; Saunders, Tara A. ; Williams, Catherine S. ; Dvorak, Katerina ; Dvorak, Bohuslav. / Epidermal growth factor reduces hepatic sequelae in experimental necrotizing enterocolitis. In: Biology of the Neonate. 2006 ; Vol. 89, No. 4. pp. 227-235.
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abstract = "Background and Aim: Neonatal necrotizing enterocolitis (NEC) is the most common gastrointestinal disease of premature infants. We recently demonstrated that the gut/liver axis plays an important role in the pathophysiology of NEC through the release of inflammatory mediators into the intestinal lumen. We have also shown that supplementation of formula with epidermal growth factor (EGF) dramatically decreases ileal pathology associated with experimental NEC. In this study, we examined the effects of EGF on the liver portion of the gut/liver axis in the neonatal rat model of NEC. Methods: Newborn rats were divided into three experimental groups, NEC, hand-fed with growth-factor free formula; NEC + EGF, hand-fed with formula supplemented with 500 ng/ml rat EGF; or DF, dam fed. All animals were exposed to asphyxia and cold stress twice daily for 4 days to develop NEC. Results: EGF receptor expression was significantly (p ≤ 0.01) decreased in the NEC + EGF group compared to the NEC group. EGF supplementation significantly decreased Kupffer cell numbers (p ≤ 0.01) as well as hepatic tumor necrosis factor (TNF)-α and interleukin-18 production (p ≤ 0.05). Further, TNF-α in the intestinal luminal contents of the NEC + EGF group were normalized to levels observed in DF controls compared to the NEC group (p ≤ 0.05). Activated nuclear factor-κB was also substantially decreased in the NEC + EGF group versus the NEC group. Conclusion: The results of this study indicate that EGF normalizes cytokine overproduction in the liver of neonatal rats with NEC, which contributes to diminished intestinal damage during the development of experimental NEC. These data suggest that supplementation of formula with EGF can have beneficial effects on the gut/liver axis during NEC pathogenesis.",
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