The effect of a selective 5-lipoxygenase inhibitor,zileuton, on tissue damage in acute colonic inflammation in rats |
| |
Authors: | Adil Zarif David Eiznhamer Charles Callaghan Manuel I Doria Laurie Broutman Ali Keshavarzian |
| |
Institution: | (1) Department of Medicine, Division of Digestive Diseases and Nutrition, Loyola University School of Medicine, Maywood, Illinois;(2) Department of Pharmacology, Loyola University School of Medicine, Maywood, Illinois;(3) Department of Pathology, Loyola University School of Medicine, Maywood, Illinois;(4) Hines Virginia, Hines, Illinois Abbott Laboratories, Medical and Research Services, Abbott Park, Illinois |
| |
Abstract: | Though the mechanism of tissue damage induced by colonic inflammation in ulcerative colitis is unknown, it has been established that the inflammatory mediator and potent neutrophil (PMN) chemotaxin, leukotriene B4(LTB4), is present in elevated amounts in the inflamed mucosa. The 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 to test the efficacy of a specific and potent 5-lipoxygenase inhibitor zileuton in the treatment of colonic inflammation. We hypothesized that 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 colonic tissue damage as measured by Histological score. However, zileuton did not significantly decrease neutrophil infiltration measured by mucosal PMN or myeloperoxidase (MPO) levels. Although zileuton was successful in significantly decreasing the frequency of severe colitis in our model, the fact that the decrease in PMN count and MPO level was not statistically significant suggests that another mechanism may be involved in its anti-inflammatory effect. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|