In vivo assessment of villous microcirculation in the rat small intestine in Indomethacin‐induced inflammation: role of mast‐cell stabilizer Ketotifen

Abstract

Indomethacin induces an inflammatory reaction in the small intestine in several rat strains. This animal model is widely used to study the implications of intestinal inflammation. Macroscopically, there is evidence that Indomethacin induces a hyperaemic inflammatory reaction in the mucosa, and in our previous studies, we found a significant increase in villous perfusion in the acutely inflamed small intestine. Mast-cell activation was found to take part in inflammatory reactions in several organ systems in various species. However, no data are available about the effect of mast-cell degranulation on the perfusion of the mucosa in Indomethacin-induced intestinal inflammation. Therefore, we used the mast-cell stabilizer Ketotifen to identify if mast-cell activation may contribute to changes in the perfusion of single villi in the rat ileum. We found that Ketotifen significantly reduced the Indomethacin induced increased blood flow in the main arteriole 60 min after i.v. application, indicating that mast-cell degranulation effects microcirculatory disturbances in the mucosa in Indomethacin-induced intestinal inflammation.

Low mast cell density in the human duodenal mucosa from chronic inflammatory duodenal bowel disorders is associated with defective villous architecture

“…Mast cells have temptatively been implicated in the pathogenesis of an heterogeneous group of inflammatory intestinal disorders, such as enteritis from food allergy [5], ulcerative colitis [6], Crohn's disease [7], microscopic colitis [8], chronic idiopathic diarrhoea [9], celiac disease [10] and eosinophilic gastroenteritis [11]. Moreover, they have been suggested to play an important role in a series of noninflammatory intestinal functions, including barrier maintenance, trans-epithelial transport of molecules and ions, intestinal motility and peristalsis, splancnic blood flow and vascular permeability [12,13].…”

Mast cells are involved in the pathogenesis of indomethacin-induced rat enteritis

“…10,11,12,13,14 In these studies, mast cell stabilizers were used to reveal that mast cells contribute to infl ammation of the small intestine, increases in oxidative stress, mucosal neutrophil infi ltration, and mucosal injury induced by indomethacin. In this study, we used mast cell-defi cient (Ws/Ws) rats to demonstrate the role of mast cells in mucosal damage of the small intestine induced by indomethacin.…”

“…4,5,6,7,8,9 Mast cells have been reported to play an important role in the pathogenesis of indomethacin-induced small intestinal mucosal injury. 10,11,12,13,14 Mast cell stabilizers were used in these previous studies. In the present study, we for the fi rst time used mast cell-defi cient Ws/ Ws rats to reveal the role of mast cells in indomethacininduced small intestinal mucosal injury.…”

Mast Cell Stabilization Alleviates Acute Lung Injury after Orthotopic Autologous Liver Transplantation in Rats by Downregulating Inflammation

“…The cromolyn sodium-binding protein expressed in MCs may inhibit calcium flux into the cell before antigen and non-antigen challenge [35], [36]. Ketotifen, which inhibits histamine receptors, can effectively prevent mediators to be released from MCs and treat allergic diseases in experimental and clinical trials [17], [37]–[43].…”