Prenatal lipopolysaccharide increases postnatal intestinal injury in a rat model of necrotizing enterocolitis.
BACKGROUND
An increased incidence of necrotizing enterocolitis (NEC) has been noted in infants who are born to mothers with chorioamnionitis.


OBJECTIVE
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.
Giannone
Peter J
PJ
Department of Pediatrics at Centers for Cardiovascular Medicine, Research Institute at Nationwide Children's Hospital, Columbus, OH 43205, USA. peter.giannone@nationwidechildrens.org
Nankervis
Craig A
CA
Richter
Juli M
JM
Schanbacher
Brandon L
BL
Reber
Kristina M
KM
D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006146:Guanidines / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000009:adverse effects*; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000097:blood; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D004791:Enzyme Inhibitors; D006146:Guanidines; D008070:Lipopolysaccharides; D009566:Nitrates; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C004479:pimagedine