Mast cells do not contribute to nonsteroidal anti-inflammatory drug-induced gastric mucosal injury in rodents.
BACKGROUND
By releasing pro-ulcerogenic mediators, mast cells may contribute to the mucosal injury associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs).


METHODS
To study this, rat and mouse models of NSAID-induced gastric damage were used in which administration of indomethacin causes haemorrhagic injury in the corpus region of the stomach, and the "re-feeding" model in which penetrating antral ulcers are induced in the rat by naproxen. Mast cell degranulation was determined histologically and by measurement of tissue and serum levels of rat mast cell protease-II, a mediator specific to mucosal mast cells. The effects of either increasing or decreasing the number of gastric mucosal mast cells on the susceptibility of the stomach to injury induced by indomethacin were also studied.


RESULTS
Gastric injury induced by indomethacin was not accompanied by significant mast cell degranulation. Moreover, neither increasing nor decreasing the number of gastric mucosal mast cells had a significant effect on the susceptibility of the gastric mucosa to damage induced by indomethacin. In the re-feeding model, prior depletion of gastric mucosal mast cells did not significantly affect the severity of antral ulceration induced by naproxen, nor the ability of prostaglandin E2 to prevent this damage. Finally, indomethacin-induced damage was similar in severity in mice with a genetic defect resulting in the complete absence of mast cells as it was in normal, congenic littermates.


CONCLUSIONS
Mast cells do not play a significant role in the development of gastric injury induced by acute NSAID administration in the rat or mouse.
Rioux
K P
KP
Intestinal Disease Research Unit, University of Calgary, Alberta, Canada.
Wallace
J L
JL
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D015550:Cell Degranulation; D003907:Dexamethasone / Q000009:adverse effects; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D007213:Indomethacin / Q000009:adverse effects; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D051379:Mice; D009288:Naproxen / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced*
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D009288:Naproxen; D003907:Dexamethasone; D007213:Indomethacin