BACKGROUND & AIMS: Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency of premature infants. While the effect of bile acids (BAs) on intestinal mucosal injury is known, we investigated the contribution of BAs during the development of NEC in neonatal rats. METHODS: Premature rats were fed with cow's milk-based formula and subjected to asphyxia and cold stress to develop NEC. Jejunal and ileal luminal BAs, portal blood BAs, and messenger RNA and protein for the apical sodium-dependent bile acid transporter, the ileal bile acid binding protein, and the heteromeric organic solute transporter (Ostalpha/Ostbeta)were evaluated. RESULTS: Ileal luminal BAs levels were increased significantly during disease development and the removal of ileal BAs significantly decreased the incidence and severity of disease. Furthermore, when NEC was reduced via treatment with epidermal growth factor (EGF), BA levels were reduced significantly. Jejunal luminal BA levels were similar between animals with NEC and controls, but portal/ileal luminal BA ratios were decreased significantly in animals with NEC. The apical sodium-dependent bile acid transporter was up-regulated at the site of injury in animals with NEC and decreased after EGF treatment; however, the ileal bile acid binding protein was up-regulated only in the NEC and EGF group. Ostalpha/Ostbeta expression was low in all groups, and only slightly increased in the NEC group. CONCLUSIONS: These data strongly suggest that BAs play a role in the development of ileal damage in experimental NEC and that alterations in BA transport in the neonatal ileum may contribute to disease development.
BACKGROUND & AIMS:Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency of premature infants. While the effect of bile acids (BAs) on intestinal mucosal injury is known, we investigated the contribution of BAs during the development of NEC in neonatal rats. METHODS: Premature rats were fed with cow's milk-based formula and subjected to asphyxia and cold stress to develop NEC. Jejunal and ileal luminal BAs, portal blood BAs, and messenger RNA and protein for the apical sodium-dependent bile acid transporter, the ileal bile acid binding protein, and the heteromeric organic solute transporter (Ostalpha/Ostbeta)were evaluated. RESULTS: Ileal luminal BAs levels were increased significantly during disease development and the removal of ileal BAs significantly decreased the incidence and severity of disease. Furthermore, when NEC was reduced via treatment with epidermal growth factor (EGF), BA levels were reduced significantly. Jejunal luminal BA levels were similar between animals with NEC and controls, but portal/ileal luminal BA ratios were decreased significantly in animals with NEC. The apical sodium-dependent bile acid transporter was up-regulated at the site of injury in animals with NEC and decreased after EGF treatment; however, the ileal bile acid binding protein was up-regulated only in the NEC and EGF group. Ostalpha/Ostbeta expression was low in all groups, and only slightly increased in the NEC group. CONCLUSIONS: These data strongly suggest that BAs play a role in the development of ileal damage in experimental NEC and that alterations in BA transport in the neonatal ileum may contribute to disease development.
Authors: D J Andorsky; D P Lund; C W Lillehei; T Jaksic; J Dicanzio; D S Richardson; S B Collier; C Lo; C Duggan Journal: J Pediatr Date: 2001-07 Impact factor: 4.406
Authors: M Gambarara; F Ferretti; P Bagolan; B Papadatou; M Rivosecchi; M C Lucchetti; A Nahom; M Castro Journal: Eur J Pediatr Surg Date: 1999-08 Impact factor: 2.191
Authors: Andrew A Maynard; Katerina Dvorak; Ludmila Khailova; Holly Dobrenen; Kelly M Arganbright; Melissa D Halpern; Ashish R Kurundkar; Akhil Maheshwari; Bohuslav Dvorak Journal: Am J Physiol Gastrointest Liver Physiol Date: 2010-06-10 Impact factor: 4.052
Authors: Alexander L Ticho; Pooja Malhotra; Pradeep K Dudeja; Ravinder K Gill; Waddah A Alrefai Journal: Compr Physiol Date: 2019-12-18 Impact factor: 9.090
Authors: Ludmila Khailova; Katerina Dvorak; Kelly M Arganbright; Catherine S Williams; Melissa D Halpern; Bohuslav Dvorak Journal: Pediatr Res Date: 2009-08 Impact factor: 3.756