Ketotifen inhibits Clostridium difficile toxin A-induced enteritis in rat ileum.
Ketotifen inhibits Clostridium difficile toxin A-induced enteritis in rat ileum.
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DOI：
10.1016/0016-5085(93)90886-h
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发表时间：
1993-09
期刊：
影响因子：
29.4
通讯作者：
C. Pothoulakis;F. Karmeli;C. Kelly;R. Eliakim;M. Joshi;C. O'keane;I. Castagliuolo;J. Lamont;D. Rachmilewitz
中科院分区：
文献类型：
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作者：
C. Pothoulakis;F. Karmeli;C. Kelly;R. Eliakim;M. Joshi;C. O'keane;I. Castagliuolo;J. Lamont;D. Rachmilewitz
背景：艰难梭菌毒素A是实验动物炎症性小肠结肠炎的主要介质。本研究的目的是探讨酮替芬，一种抗炎药，对毒素A诱导的肠毒性在大鼠ileum.Methods：酮替芬灌胃的分泌，甘露醇渗透性，组织学损伤的影响，和白三烯B4，白三烯C4，和血小板活化因子在毒素A暴露大鼠回肠袢粘膜水平在体内进行了测定。酮替芬对毒素A介导的大鼠肥大细胞蛋白酶II（大鼠粘膜肥大细胞产物）释放的影响也在体外大鼠回肠外植体中测定。酮替芬对中性粒细胞迁移的影响在体外evaluated.Results：酮替芬预处理抑制毒素A相关的肠道分泌的42.5%和甘露醇的渗透性56.3%，减少上皮细胞的炎症和坏死。这些作用与白三烯B465.8%，白三烯C488.8%，血小板活化因子77.8%，大鼠肥大细胞蛋白酶II抑制58.4%。此外，与酮替芬的中性粒细胞的预处理抑制中性粒细胞migration in vitro.Conclusions：酮替芬在这种动物模型中的保护作用与显着抑制肥大细胞和中性粒细胞衍生的介质的释放，支持他们参与inC。艰难肠炎
Background:Clostridium difficiletoxin A is the principal mediator of inflammatory enterocolitis in experimental animals. The purpose of this study was to explore the effect of ketotifen, an anti-inflammatory drug, on toxin A-induced enterotoxicity in rat ileum.Methods: The effects of intragastric administration of ketotifen on secretion, mannitol permeability, histological damage, and mucosal levels of leukotriene B4, leukotriene C4, and platelet activating factor in toxin A-exposed rat ileal loops were measured in vivo. The effects of ketotifen on toxin A-mediated release of rat mast cell protease II (rat mucosa mast cell product) release were also measured in rat ileal explants in vitro. The effect of ketotifen on neutrophil migration in vitro was also evaluated.Results:Ketotifen pretreatment inhibited toxin A-associated intestinal secretion by 42.5% and mannitol permeability by 56.3% and reduced epithelial cell inflammation and necrosis. These effects were associated with reduced levels of leukotriene B4by 65.8%, leukotriene C4by 88.8%, platelet activating factor by 77.8%, and inhibition of rat mast cell protease II by 58.4%. In addition, pretreatment of neutrophils with ketotifen inhibited neutrophil migration in vitro.Conclusions:The protective effect of ketotifen in this animal model was associated with significant inhibition of release of mast cells and neutrophil derived mediators, supporting their involvement inC. difficileenteritis.