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Publication : Mast cells are critical for protection against peptic ulcers induced by the NSAID piroxicam.

First Author  Hampton DD Year  2011
Journal  PLoS One Volume  6
Issue  8 Pages  e23669
PubMed ID  21858200 Mgi Jnum  J:176357
Mgi Id  MGI:5291534 Doi  10.1371/journal.pone.0023669
Citation  Hampton DD, et al. (2011) Mast cells are critical for protection against peptic ulcers induced by the NSAID piroxicam. PLoS One 6(8):e23669
abstractText  Many commonly used non-steroidal anti-inflammatory drugs (NSAIDs) also cause gastrointestinal toxicity, including the development of life-threatening peptic ulcers. We report that mast cell-deficient mice have an extremely high incidence of severe peptic ulceration when exposed to the NSAID piroxicam. This enhanced ulcer susceptibility can be reversed by reconstitution with mast cells. Furthermore, wild type mice treated with diphenhydramine hydrochloride, a commonly used antihistamine that blocks histamine H1 receptors, develop a similarly high incidence of peptic ulcers following piroxicam exposure. The protective effect of mast cells is independent of TNF, blockade of H2 receptors, or acid secretion. These data indicate a critical role for mast cells and the histamine that they produce in prevention and/or repair of piroxicam-induced gastric mucosal injury. Additional studies will be required to determine whether this represents a NSAID class effect that can be exploited to develop novel therapeutic strategies to limit the incidence of NSAID-induced side effects in humans.
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