title: Bacterial translocation is inhibited in inducible nitric oxide synthase knockout mice after endotoxin challenge but not in a model of bacterial overgrowth.
abstract: BACKGROUND
  Studies have shown that nitric oxide (NO) and NO synthase (NOS) inhibitors injure and protect organs after endotoxin (lipopolysaccharide [LPS]) challenge.
  
  
  OBJECTIVE
  To test the hypothesis that LPS-induced gut injury and bacterial translocation (BT) are mediated through activation of inducible NOS (iNOS).
  
  
  METHODS
  A randomized, controlled study using genetically altered, iNOS gene knockout mice.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Forty-five wild-type (iNOS+/+) or homozygous mutant (iNOS-/-) mice weighing 25 to 35 g were challenged with Escherichia coli LPS or saline (10 mg/ kg) intraperitoneally (n = 8/group). In a second set of experiments, a bacterial overgrowth model of BT (E coli monoassociation) was tested (n = 6-7/group). The mesenteric lymph nodes and cecums were cultured, and liver, ileal, and blood nitrite and nitrate levels measured 24 hours after LPS or E coli monoassociation.
  
  
  RESULTS
  After LPS challenge, 87.5% of the iNOS+/+ mice but 0% of the iNOS-/- mice had BT to their mesenteric lymph nodes (P < .01; chi 2 analysis). Nitrite and nitrate levels of the liver, ileum, and blood were higher in the iNOS+/+ mice (P < .05). In the E coli overgrowth model, BT to mesenteric lymph nodes occurred in 100% of iNOS-/- and iNOS+/+ mice.
  
  
  CONCLUSIONS
  In this limited study, LPS-induced BT did not occur in iNOS-deficient mice, suggesting that LPS induction of increased iNOS activity is necessary for LPS-induced BT to occur. In contrast, iNOS activation does not seem to be necessary in a bacterial overgrowth model of BT.
authors.affiliation: Department of Surgery, UMDNJ-New Jersey Medical School, Newark, USA.
authors.forename: S
authors.initials: S
authors.lastname: Mishima
authors.forename: D
authors.initials: D
authors.lastname: Xu
authors.forename: Q
authors.initials: Q
authors.lastname: Lu
authors.forename: E A
authors.initials: EA
authors.lastname: Deitch
mesh_terms: D000818:Animals; D018988:Bacterial Translocation / Q000502:physiology*; D004926:Escherichia coli; D008070:Lipopolysaccharides / Q000008:administration & dosage; D051379:Mice; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000502:physiology*
chemical_list: D008070:Lipopolysaccharides; D019001:Nitric Oxide Synthase