Factors and mechanisms involved in epithelial injury and repair of equine colon

Gastrointestinal disease is one of the leading causes of death on horses over 30 days in age and is often associated with injury to or loss of gastrointestinal epithelium. Rapid repair of epithelium is crucial to recovery. We evaluated the effects of several potential modulators (phenylbutazone, indomethacin, glutamine, butyrate, prostaglandin E2, acetylcysteine) on epithelial repair in vivo and in vitro. We also described the distribution of the pro-inflammatory eosinophilic granulocyte in the gastrointestinal mucosa of normal and diseased horses, as well as the mucosal eosinophilic response to a variety of stimuli in vitro and in vivo.; Models of mucosal injury used in these studies include ischemia/reperfusion injury, castor oil induced colitis, HOCl induced oxidative injury and parasite induced gastrointestinal disease. In vitro experiments were performed in Ussing chambers, and transepithelial resistance and mannitol permeability were evaluated. Additional investigations were performed using histology, scintillation counting and microarray analysis.; Of the modulators evaluated, glutamine and acetylcysteine had beneficial effects on epithelial recovery, and nonsteroidal anti-inflammatory drugs did not interfere with epithelial repair. Acetylcysteine caused an increase in mucosal permeability to mannitol. Eosinophils were present in the gastrointestinal tract of all horses and followed a clear pattern of distribution. Most eosinophils were present in the cecum, ascending colon and transverse colon, and eosinophils were located in the half of the lamina propria closest to the muscularis mucosae under normal conditions. Strangulating lesions, ischemia/reperfusion, parasite infection and HOCl-induced injury resulted in accumulation and migration of eosinophils in vivo and in vitro. Cytokines likely to be involved with the eosinophilic response to ischemia/reperfusion included eotaxin and tumor necrosis factor alpha.; We concluded that acetylcysteine and glutamine might be beneficial in the treatment of horses with gastrointestinal disease. The increase of mucosal permeability caused by acetylcysteine may be caused by the mucolytic properties of acetylcysteine. A lower dose may prevent mucolysis while allowing for the beneficial effects of acetylcysteine. Eosinophils were involved in several disease processes of the gastrointestinal tract in horses. They may be part of an initial inflammatory response of gastrointestinal mucosa to injury, and could have detrimental effects in several diseases including ischemia/reperfusion.