title: The efficacy of BAY y 1015 in dextran sulfate model of mouse colitis.
abstract: OBJECTIVE
  There is crucial evidence that leukotrienes are significant mediators of inflammation in inflammatory bowel diseases (IBD). Thus, selective inhibition of leukotriene synthesis is believed to provide a novel approach to therapy of IBD. The aim of the study is to study the efficacy of a potent 5-lipoxygenase activating protein inhibitor (FLAP), BAY y 1015 in a dextran sulfate model of mouse colitis.
  
  
  METHODS
  Outbred female mice weighing approximately 25 grams were used to produce acute or chronic colitis by feeding 5% dextran sulfate in drinking water.
  
  
  METHODS
  Colitic mice were treated with placebo (3% starch suspension, 0.1 ml. p.o., bid) or BAY y 1015 at 8 or 24 mg/kg, p.o., bid or olsalazine, 150 mg/kg/day, p.o.
  
  
  METHODS
  Efficacy was determined by measuring daily disease activity index (DAI), quantitative histological scores, qualitative histology and measurement of tissue myeloperoxidase (MPO) and leukotriene B4 (LTB4) levels.
  
  
  RESULTS
  BAY y 1015 was significantly more effective in improving the qualitative histology, inhibiting the DAI, inflammation scores (37-79%), crypt scores (28-71%), MPO (49-57%) and LTB4 levels (56-63%) compared to placebo treatment at all levels of colitis. The two doses of BAY y 1015 were equipotent in decreasing TLB4 levels. BAY y 1015 was significantly better than olsalazine in two of the three protocols used in this study. In the advanced disease level both doses of BAY y 1015 were equipotent in inhibiting crypt and (28-32%) inflammation scores (34-36%), LTB4 (34-56%) and MPO 41-49%) compared to olsalazine.
  
  
  CONCLUSIONS
  This study suggests the possibility of investigating the use of this compound for the treatment of human inflammatory bowel diseases.
authors.affiliation: Krancer Center for IBD Research, Division of Gastroenterology and Hepatology, Allegheny University of the Health Sciences, Philadelphia, PA 19102-1192, USA. murthys@allegheny.edu
authors.forename: S
authors.initials: S
authors.lastname: Murthy
authors.forename: N S
authors.initials: NS
authors.lastname: Murthy
authors.forename: D
authors.initials: D
authors.lastname: Coppola
authors.forename: D L
authors.initials: DL
authors.lastname: Wood
mesh_terms: D000818:Animals; D003092:Colitis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D005260:Female; D007975:Leukotriene B4 / Q000032:analysis; D016859:Lipoxygenase Inhibitors / Q000627:therapeutic use*; D051379:Mice; D009195:Peroxidase / Q000378:metabolism; D011804:Quinolines / Q000627:therapeutic use*
chemical_list: C099016:Bay y 1015; D016859:Lipoxygenase Inhibitors; D011804:Quinolines; D007975:Leukotriene B4; D016264:Dextran Sulfate; D009195:Peroxidase