The efficacy of BAY y 1015 in dextran sulfate model of mouse colitis.

Abstract

OBJECTIVE AND DESIGN:

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.

MATERIAL:

Outbred female mice weighing approximately 25 grams were used to produce acute or chronic colitis by feeding 5% dextran sulfate in drinking water.

TREATMENT:

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.

CONCLUSION:

This study suggests the possibility of investigating the use of this compound for the treatment of human inflammatory bowel diseases.

• Authors: S Murthy, N S Murthy, D Coppola, D L Wood
• Journal: Inflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 46 Issue 6 Pg. 224-33 (Jun 1997) ISSN: 1023-3830 [Print] Switzerland
• PMID: 9243306 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bay y 1015
• Lipoxygenase Inhibitors
• Quinolines
• Leukotriene B4
• Dextran Sulfate
• Peroxidase

Topics

• Animals
• Colitis (drug therapy, metabolism, pathology)
• Dextran Sulfate
• Disease Models, Animal
• Female
• Leukotriene B4 (analysis)
• Lipoxygenase Inhibitors (therapeutic use)
• Mice
• Peroxidase (metabolism)
• Quinolines (therapeutic use)