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.
Slomiany
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BL
Research Center, University of Medicine and Dentistry of New Jersey, Newark 07103-2400, USA. slomiabr@umdnj.edu
Slomiany
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A
D019342:Acetic Acid / Q000633:toxicity; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D001241:Aspirin / Q000008:administration & dosage / Q000009:adverse effects*; D002462:Cell Membrane / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006877:Hydroxamic Acids / Q000494:pharmacology; D009061:Mouth Mucosa / Q000187:drug effects* / Q000378:metabolism; D019226:Oral Ulcer / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014945:Wound Healing / Q000187:drug effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006877:Hydroxamic Acids; D011480:Protease Inhibitors; D014409:Tumor Necrosis Factor-alpha; C048727:zincov; D019342:Acetic Acid; D001241:Aspirin