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Inflamm Res. 1997 Jun;46(6):224-33.

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

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Krancer Center for IBD Research, Division of Gastroenterology and Hepatology, Allegheny University of the Health Sciences, Philadelphia, PA 19102-1192, USA.



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.


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


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.


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.


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.


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

[Indexed for MEDLINE]

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