THE EFFECT OF A SELECTIVE 5-LIPOXYGENASE INHIBITOR, ZILEUTON, ON TISSUE-DAMAGE IN ACUTE COLONIC INFLAMMATION IN RATS

Though the mechanism of tissue damage induced by colonic inflammation in ulcerative colitis is unknown, it has been established that the inf lammatory mediator and potent neutrophil (PMN) chemotaxin, leukotriene B4(LTB(4)), is present in elevated amounts in the inflamed mucosa. Th e unique role of 5-lipoxygenase in the production of leukotrienes has made it a target for inhibition. This study used a rat model of acute colonic inflammation induced by a single IP injection of Mitomycin-C t o test the efficacy of a specific and potent 5-lipoxygenase inhibitor zileuton in the treatment of colonic inflammation. We hypothesized tha t after inducing colitis in rats with mitomycin-C, the administration of oral zileuton would inhibit leukotriene production, thus preventing PMN infiltration and subsequent tissue damage. Zileuton decreased col onic tissue damage as measured by Histological score. However, zileuto n did not significantly decrease neutrophil infiltration measured by m ucosal PMN or myeloperoxidase (MPO) levels. Although zileuton was succ essful in significantly decreasing the frequency of severe colitis in our model, the fact that the decrease in PMN count and MPO Level was n ot statistically significant suggests that another mechanism may be in volved in its anti-inflammatory effect.