Prenatal lipopolysaccharide increases postnatal intestinal injury in a rat model of necrotizing enterocolitis

J Pediatr Gastroenterol Nutr. 2009 Mar;48(3):276-82. doi: 10.1097/mpg.0b013e31818936b8.

Abstract

Background: An increased incidence of necrotizing enterocolitis (NEC) has been noted in infants who are born to mothers with chorioamnionitis.

Hypothesis: Our objective was to test the hypothesis that newborn rat pups born to mothers exposed to prenatal lipopolysaccharide during pregnancy would be more susceptible to intestinal injury in a rat model of NEC and that the increased intestinal injury is mediated by dysregulation of inducible nitric oxide synthase.

Methods: Time-dated pregnant Sprague-Dawley dams were given an intraperitoneal injection of either 2 mg/kg of lipopolysaccharide or vehicle. Rat pups from each group of dams were delivered at term and placed in a rat NEC model. A subset of pups was given either vehicle or aminoguanidine. Intestines were harvested and graded for degree of intestinal injury.

Results: Maternal prenatal lipopolysaccharide exposure increased the frequency and severity of intestinal injury in the neonatal rat NEC model. Treatment with aminoguanidine significantly decreased plasma nitric oxide levels. Additionally, aminoguanidine significantly decreased intestinal injury.

Conclusions: Intestinal injury observed may be mediated via nitric oxide synthase dysregulation.

MeSH terms

  • Animals
  • Animals, Newborn
  • Blood Pressure / drug effects
  • Disease Models, Animal
  • Enterocolitis, Necrotizing / drug therapy
  • Enterocolitis, Necrotizing / etiology*
  • Enterocolitis, Necrotizing / physiopathology
  • Enzyme Inhibitors / therapeutic use*
  • Female
  • Guanidines / therapeutic use*
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / physiopathology
  • Lipopolysaccharides / adverse effects*
  • Nitrates / blood
  • Nitric Oxide / blood
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism*
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Enzyme Inhibitors
  • Guanidines
  • Lipopolysaccharides
  • Nitrates
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Nitric Oxide Synthase
  • pimagedine