NSAID-Induced Mucosal Injury: Analysis of Gastric Toxicity with New Generation NSAIDs: Ulcerogenicity Compared with Ulcer Healing

INTRODUCTION: Some non-steroidal anti-inflammatory drugs (NSAIDs) delay healing of experimental gastric ulcers. The two experimental NSAIDs tebufelone and nitrofenac exert relatively low ulcerogenicity in various animal models compared with conventional NSAIDs. In addition, it has been reported that nitrofenac accelerates experimental acute ulcer healing. However, the effects of these new NSAIDs in a reliable chronic ulcer model has not been fully established. METHODS: Ulcerogenicity of tebufelone was compared with vehicle and indomethacin in arthritic female Lewis rats in a single dose and a 5-day dosage study. Interference with ulcer healing of tebufelone and nitrofenac was compared with vehicle, indomethacin, diclofenac, omeprazole, and indomethacin plus omeprazole in Wistar rats with gastric cryo-ulcers. The rats were treated for 15 days and ulcer size was sequentially quantified by video endoscopy. Prostanoid synthesis in stomach and blood were assessed on day 15. RESULTS: Ulcerogenicity of tebufelone was markedly lower than that of indomethacin using doses with equipotent anti-inflammatory activities. Ulcer healing was accelerated by omeprazole in the first week, but significantly delayed by tebufelone and nitrofenac to a similar extent as indomethacin and diclofenac predominantly during the second week. All NSAIDs decreased prostanoid synthesis. CONCLUSION: Tebufelone and nitrofenac delayed gastric ulcer healing to a similar extent as conventional NSAIDs even though tebufelone appears to induce less mucosal damage when determined in standard ulcer assays in rats. Thus there does not appear to be a relationship between ulcerogenicity of these NSAIDs and their behaviour in ulcer healing.