Aspirin ingestion impairs oral mucosal ulcer healing by inducing membrane-bound tumor necrosis factor-alpha release

Among the early manifestations of impairment by nonsteroidal anti-inflammatory drugs in mucosal tissue repair is the enhancement in tumor necrosis factor-alpha (TNF-alpha). We investigated the effect of aspirin ingestion on the processing of TNF-alpha in rat soft oral tissue during buccal ulcer healing. While in the control group, the ulcer healed by the 10th day; only a 54.8% reduction in the ulcer area was attained in the presence of aspirin administration. Moreover, by the 10th day, the delay in ulcer healing by aspirin was manifested in a 5.6-fold higher rate of apoptosis and a 5.2-fold higher level of soluble TNF-alpha, yet the expression of membrane-bound TNF-alpha showed a 38% decline. Treatment with metalloprotease inhibitor, Zincov, produced dose-dependent reduction (56.9%) in aspirin-induced increase in the mucosal expression of soluble TNF-alpha, evoked a 62% decrease in the rate of epithelial cell apoptosis, and led to a marked reversal (56.9%) in aspirin-induced delay in ulcer healing. Our findings indicate that the impairment in buccal ulcer healing by aspirin is a result of upregulation in the processing of soluble TNF-alpha from its membrane-bound precursor that leads to the amplification of apoptotic events and potentiation of the mucosal inflammatory responses that interfere with healing process.