Background: Nonsteroidal antiinflammatory drug (NSAID)-induced enteropathy is clinically very important, but the pathological mechanisms remain unclear. Mast cells have been reported to play an important role in the pathogenesis of indomethacin-induced small intestinal injury. In this study, we investigated the role of mast cells in indomethacin-induced small intestinal injury using mast cell deficiency (Ws/Ws) rat.
Methods: Ws/Ws rats and control (W+/W+) rats were given indomethacin (15 mg/kg) subcutaneously, and the intestinal mucosal damage was estimated after 24 h.
Results: The area (mm2) of macroscopic visible lesions, the concentrations of thiobarbituric acid-reactive substances (TBARS) as an index of lipid peroxidation, myeloperoxidase (MPO) activity as an index of neutrophil accumulation, and the content of cytokine-induced neutrophil chemoattractant-1 (CINC-1) were significantly increased in indomethacin-treated groups compared with the sham groups. The development of intestinal lesions in response to indomethacin was prevented in Ws/Ws rats compared with W+/W+ rats, together with significant suppression of the increased levels of TBARS, MPO activities, and CINC-1 levels.
Conclusions: These results indicate that mast cells are involved in the pathogenesis of the intestinal mucosal damage induced by indomethacin.