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

Abstract

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.

• Authors: B L Slomiany, A Slomiany
• Journal: IUBMB life (IUBMB Life) Vol. 50 Issue 6 Pg. 391-5 (Dec 2000) ISSN: 1521-6543 [Print] England
• PMID: 11327313 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Hydroxamic Acids
• Protease Inhibitors
• Tumor Necrosis Factor-alpha
• zincov
• Acetic Acid
• Aspirin

Topics

• Acetic Acid (toxicity)
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage, adverse effects)
• Aspirin (administration & dosage, adverse effects)
• Cell Membrane (metabolism)
• Dose-Response Relationship, Drug
• Hydroxamic Acids (pharmacology)
• Mouth Mucosa (drug effects, metabolism)
• Oral Ulcer (chemically induced, drug therapy, physiopathology)
• Protease Inhibitors (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Tumor Necrosis Factor-alpha (metabolism)
• Wound Healing (drug effects)