Comparison of epidermal growth factor and heparin-binding epidermal growth factor-like growth factor for prevention of experimental necrotizing enterocolitis.
BACKGROUND
Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of prematurely born infants. Epidermal growth factor (EGF) and heparin-binding EGF-like growth factor (HB-EGF) have protective effects against intestinal injury. The aim of this study was to compare the effect of oral administration of HB-EGF, EGF, or both on the incidence of NEC in a neonatal rat model.


METHODS
Premature rats were fed by hand and exposed to asphyxia and cold stress to develop NEC. Four diets were used: formula (NEC), formula supplemented with 500 ng/mL HB-EGF (HB), 500 ng/mL EGF (EGF), or a combination of both (E+HB). Ileal injury, endogenous HB-EGF production, expression of EGF receptors, goblet cell density, and expression of apoptotic proteins were evaluated.


RESULTS
Oral administration of either EGF or HB-EGF significantly reduced the incidence of NEC; however, EGF provided better protection in physiologically relevant doses. Simultaneous administration of both growth factors did not result in any synergistic protective effect against NEC. There were no significant differences between treatment groups in ileal gene expression of EGF receptors or HB-EGF. However, the balance of apoptotic proteins in the ileum was shifted in favor of cell survival in EGF-treated rats. This mechanism may be responsible for the higher efficiency of EGF protection against NEC.


CONCLUSIONS
These data suggest that a physiological dosage of EGF or a pharmacological dosage of HB-EGF could be used for prevention of NEC.
Dvorak
Bohuslav
B
Department of Pediatrics, Steele Children's Research Center, University of Arizona, Tucson, AZ 85724-5073, USA. dvorakb@peds.arizona.edu
Khailova
Ludmila
L
Clark
Jessica A
JA
Hosseini
Dania Molla
DM
Arganbright
Kelly M
KM
Reynolds
Charity A
CA
Halpern
Melissa D
MD
D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D020345:Enterocolitis, Necrotizing / Q000453:epidemiology / Q000473:pathology / Q000517:prevention & control*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066257:Heparin-binding EGF-like Growth Factor; D007082:Ileum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome
C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D004815:Epidermal Growth Factor