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Polyelectrolyte Complex for Heparin Binding Domain Osteogenic Growth Factor Delivery
Published on: August 22, 2016
Heparin-binding epidermal growth factor-like growth factor decreases the incidence of necrotizing enterocolitis in
Jiexiong Feng1, Osama N El-Assal, Gail E Besner
1Department of Surgery, Children's Hospital, and Ohio State University College of Medicine and Public Health, Columbus, OH 43205, USA.
Purpose:
We have previously demonstrated that heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a potent intestinal cytoprotective agent. The aim of this study was to determine the effect of enterally administered HB-EGF on the incidence of necrotizing enterocolitis (NEC) in neonatal rats.
Methods:
Necrotizing enterocolitis was induced in neonatal rats delivered by C-section on day 21 of gestation by exposure to repeated cycles of hypoxia and hypothermia plus administration of hypertonic formula feeding (HHHTF) plus enteral administration of lipopolysaccharide (LPS) (2 mg/kg). Neonatal rats were randomly assigned to breast-feeding, hypertonic formula feeding, HHHTF + LPS, and HHHTF + LPS with HB-EGF (600 mug/kg) supplementation in the formula. Animals were monitored until 96 hours of life and assessed for death, histological NEC, and intestinal mucosal permeability.
Results:
The incidence of NEC in the HHHTF group was higher than that in the breast-feeding or hypertonic formula feeding groups. With administration of HB-EGF, the incidence and severity of NEC were significantly decreased. Administration of HB-EGF also increased rat pup survival rate and extended survival time. In addition, treatment with HB-EGF significantly decreased intestinal permeability to fluorescein isothiocyanate-dextran.
Conclusions:
We conclude that HB-EGF reduces the incidence and severity of NEC in a neonatal rat model, with simultaneous preservation of gut barrier integrity. These results support our contention that HB-EGF administration may represent a useful therapeutic and prophylactic therapy for the treatment of NEC.
