All-trans-retinoic acid attenuates intestinal injury in a neonatal rat model of necrotizing enterocolitis

Neonatology. 2013;104(1):22-7. doi: 10.1159/000350510. Epub 2013 Apr 23.


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°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-α 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.

MeSH terms

  • Animals
  • Animals, Newborn*
  • Anti-Inflammatory Agents / administration & dosage*
  • Antioxidants / administration & dosage*
  • Cold Temperature
  • Disease Models, Animal
  • Enterocolitis, Necrotizing / etiology
  • Enterocolitis, Necrotizing / pathology*
  • Enterocolitis, Necrotizing / prevention & control
  • Glutathione Peroxidase / metabolism
  • Hypertonic Solutions
  • Hypoxia
  • Injections, Intraperitoneal
  • Intestinal Mucosa / chemistry
  • Intestinal Mucosa / pathology
  • Intestines / pathology*
  • Malondialdehyde / analysis
  • Oxidative Stress
  • Rats
  • Rats, Wistar
  • Superoxide Dismutase / metabolism
  • Tretinoin / administration & dosage*
  • Tumor Necrosis Factor-alpha / analysis


  • Anti-Inflammatory Agents
  • Antioxidants
  • Hypertonic Solutions
  • Tumor Necrosis Factor-alpha
  • Malondialdehyde
  • Tretinoin
  • Glutathione Peroxidase
  • Superoxide Dismutase