Delay in oral mucosal ulcer healing by aspirin is linked to the disturbances in p38 mitogen-activated protein kinase activation

Background: Among the early manifestations of oral mucosal impairment by no nsteroidal anti-inflammatory drugs is the delay in soft oral tissue repair brought about by the amplification of apoptotic events. In this study, we i nvestigated the effect of a specific inhibitor of p38 mitogen-activated pro tein kinase (p38 MAPK), SE 203580, on the rate of buccal mucosal ulcer heal ing and the apoptotic processes in rats subjected to intragastric administr ation of aspirin. Methods: Groups of rats with experimentally induced bucca l mucosal ulcers were administered twice daily For 10 days with SB 203580 ( 5, 10, and 20 mg/kg) or vehicle followed 30 min later by concomitant admini stration (twice daily for 10 days) of aspirin at 20 mg/kg. The animals were killed at different periods of treatment and their mucosal tissue subjecte d to macroscopic assessment of ulcer healing rate, measurement of soluble t umor necrosis factor-alpha (TNF-alpha), and the assay of epithelial cell ap optosis. Results: In the control group the ulcer healed by the tenth day an d the rate of healing was not affected by SE 203580 administration, whereas a 54.8% reduction in the ulcer area was attained in the presence of aspiri n administration. Moreover, by the tenth day, the delay in ulcer healing ca used by aspirin was manifested in a 5.6-fold higher rate of apoptosis and a 5.2-fold higher level of soluble TNF-alpha. Treatment with SE 203580 produ ced dose-dependent reduction (59.5-74.8 %) in aspirin-induced increase in t he mucosal level of soluble TNF-alpha, evoked 53.2-69.7% decrease in the ra te of epithelial cell apoptosis, and led to a marked reversal (51.8-73.9%) in aspirin-induced delay in ulcer healing. Conclusions: The results of our findings link the delay in buccal mucosal ulcer healing caused by aspirin i ngestion to the disturbances in the p38 MAPK activation.