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 nonsteroidal anti-inflammatory drugs is the delay in soft oral tissue repair brought about by the amplification of apoptotic events. In this study, we investigated the effect of a specific inhibitor of p38 mitogen-activated protein kinase (p38 MAPK), SB 203580, on the rate of buccal mucosal ulcer healing and the apoptotic processes in rats subjected to intragastric administration of aspirin.


METHODS
Groups of rats with experimentally induced buccal 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 administration (twice daily for 10 days) of aspirin at 20 mg/kg. The animals were killed at different periods of treatment and their mucosal tissue subjected to macroscopic assessment of ulcer healing rate, measurement of soluble tumor necrosis factor-alpha (TNF-alpha), and the assay of epithelial cell apoptosis.


RESULTS
In the control group the ulcer healed by the tenth day and the rate of healing was not affected by SB 203580 administration, whereas a 54.8% reduction in the ulcer area was attained in the presence of aspirin administration. Moreover, by the tenth day, the delay in ulcer healing caused 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 SB 203580 produced dose-dependent reduction (59.5-74.8%) in aspirin-induced increase in the mucosal level of soluble TNF-alpha, evoked 53.2-69.7% decrease in the rate 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 ingestion to the disturbances in the p38 MAPK activation.
Slomiany
B L
BL
Research Center University of Medicine and Dentistry of New Jersey Newark 07103-2400, USA. slomibr@umdnj.edu
Slomiany
A
A
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001241:Aspirin / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009061:Mouth Mucosa / Q000187:drug effects* / Q000201:enzymology*; D019226:Oral Ulcer / Q000188:drug therapy / Q000201:enzymology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D048051:p38 Mitogen-Activated Protein Kinases
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; D001241:Aspirin