TY - JOUR
T1 - Prenatal lipopolysaccharide increases postnatal intestinal injury in a rat model of necrotizing enterocolitis
AU - Giannone, Peter J.
AU - Nankervis, Craig A.
AU - Richter, Juli M.
AU - Schanbacher, Brandon L.
AU - Reber, Kristina M.
PY - 2009/3
Y1 - 2009/3
N2 - 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.
AB - 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.
KW - Inducible nitric oxide synthase
KW - Inflammation
KW - Intestine
KW - Necrotizing enterocolitis
KW - Prenatal
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U2 - 10.1097/MPG.0b013e31818936b8
DO - 10.1097/MPG.0b013e31818936b8
M3 - Article
C2 - 19274780
AN - SCOPUS:67650382107
SN - 0277-2116
VL - 48
SP - 276
EP - 282
JO - Journal of Pediatric Gastroenterology and Nutrition
JF - Journal of Pediatric Gastroenterology and Nutrition
IS - 3
ER -