All-Trans-Retinoic Acid Attenuates Intestinal Injury in a Neonatal Rat Model of Necrotizing Enterocolitis

ÖZDEMİR R., Yurttutan S., Sari F. N. , Oncel M. Y. , ERDEVE Ö., Unverdi H. G. , ...More

NEONATOLOGY, vol.104, no.1, pp.22-27, 2013 (Peer-Reviewed Journal) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 104 Issue: 1
  • Publication Date: 2013
  • Doi Number: 10.1159/000350510
  • Journal Name: NEONATOLOGY
  • Journal Indexes: Science Citation Index Expanded, Scopus
  • Page Numbers: pp.22-27


Background: Ischemia/reperfusion-induced intestinal injury is mediated by reactive oxygen species and inflammatory mediators. Objectives: This study was designed to evaluate whether all-trans-retinoic acid (ATRA) administration can attenuate intestinal injury and to analyze the antioxidant and anti-inflammatory effects of ATRA in a neonatal rat model of necrotizing enterocolitis (NEC). Methods: Twenty-nine Wistar albino rat pups were randomly divided into 3 groups: group 1 = control, group 2 = NEC and saline, and group 3 = NEC and ATRA treatment. NEC was induced by hyperosmolar enteral formula feeding and exposure to hypoxia after cold stress at +4 degrees C and oxygen. Pups in group 3 were injected intraperitoneally with ATRA (0.5 mg/kg body weight) once a day prior to each NEC procedure, beginning on postnatal day 1 and daily through postnatal day 4. The pups were killed on the 4th day and their intestinal tissues were harvested for biochemical and histopathological analysis. Results: Mucosal injury scores and intestinal malondialdehyde levels in group 2 were found to be significantly higher than other groups (p < 0.05). Intestinal superoxide dismutase and glutathione peroxidase activities in group 3 were significantly higher than group 2 (p = 0.04 and p = 0.04, respectively). Intestinal tissue tumor necrosis factor-alpha levels were significantly reduced with ATRA treatment in group 3 compared to group 2 (p < 0.001). Conclusions: It is likely that oxidative stress and inflammatory mediators contributed to the pathogenesis of NEC and that ATRA had a protective effect on intestinal injury through its anti-inflammatory and antioxidant properties. Copyright (c) 2013 S. Karger AG, Basel