Mast cells are involved in the pathogenesis of indomethacin-induced rat enteritis.
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.
Okayama
Tetsuya
T
Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, 602-8566, Japan.
Yoshida
Norimasa
N
Uchiyama
Kazuhiko
K
Takagi
Tomohisa
T
Ichikawa
Hiroshi
H
Yoshikawa
Toshikazu
T
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D054360:Chemokine CXCL1 / Q000187:drug effects / Q000378:metabolism; D004751:Enteritis / Q000139:chemically induced*; D007213:Indomethacin / Q000633:toxicity*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D054360:Chemokine CXCL1; C513297:Cxcl1 protein, rat; D017392:Thiobarbituric Acid Reactive Substances; D009195:Peroxidase; D007213:Indomethacin