title: Intrarectal nitric oxide administration prevents cellular infiltration but not colonic injury during dextran sodium sulfate colitis.
abstract: BACKGROUND
  During inflammation in the gastrointestinal tract, the production of nitric oxide (NO) is mediated by the mucosal conversion of L-arginine. Recently, it was shown that the gut microbiota can also produce NO.
  
  
  OBJECTIVE
  The effect of gut luminal NO on inflammatory processes of an experimental colitis mice model was investigated by administrating NO directly to the colon, mimicking microbial NO production.
  
  
  METHODS
  Twenty-four mice received daily intrarectal treatment with a NO donor in 2 doses and 8 mice were treated with placebo. Starting 1 day later, 18 of these mice were fed ad libitum with 4% of dextran sodium sulfate (DSS) in their drinking water to induce colitis. At day 6, histopathology (both the inflammation and damage score), myeloperoxidase (MPO)-activity, colon length and colonic permeability were evaluated.
  
  
  RESULTS
  Co-administration of NO during DSS exposure inhibited the induction of an increasing colonic MPO-activity. This protective effect of NO was confirmed by the histological inflammation score showing a similar trend. The colonic permeability was restored when very low levels of NO were administered to the DSS-mice. On the other hand, the colon length of the NO-treated DSS-mice was negatively correlated with the NO dose and the histological damage score was not improved.
  
  
  CONCLUSIONS
  Our results indicate that intrarectal administration of NO has clear anti-inflammatory effects in experimental colitis, but does not prevent colonic damage. Therefore, NO-producing microorganisms in the gut lumen should be accounted as a modulating process during colitis.
authors.affiliation: Faculty of Bioscience Engineering, Laboratory of Microbial Ecology and Technology, Ghent University, Ghent, Belgium.
authors.forename: Joan
authors.initials: J
authors.lastname: Vermeiren
authors.forename: Pieter
authors.initials: P
authors.lastname: Hindryckx
authors.forename: Glynn
authors.initials: G
authors.lastname: Van Nieuwenhuyse
authors.forename: Debby
authors.initials: D
authors.lastname: Laukens
authors.forename: Martine
authors.initials: M
authors.lastname: De Vos
authors.forename: Nico
authors.initials: N
authors.lastname: Boon
authors.forename: Tom
authors.initials: T
authors.lastname: Van de Wiele
mesh_terms: D000285:Administration, Rectal; D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D016264:Dextran Sulfate / Q000009:adverse effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D051379:Mice; D008815:Mice, Inbred Strains; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology*; D009195:Peroxidase / Q000378:metabolism; D012720:Severity of Illness Index
chemical_list: D009569:Nitric Oxide; D016264:Dextran Sulfate; D009195:Peroxidase