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Neither antioxidants nor COX-2 inhibition protect against esophageal inflammation in an experimental model of severe reflux.

Murphy JO, Ravi N, Byrne PJ, McDonald GS, Reynolds JV

Department of Surgery, St. James's Hospital and Trinity College, Dublin, Ireland.

BACKGROUND: Reflux-induced injury and oxidative stress result in esophageal inflammation and the potential for progression to intestinal metaplasia and adenocarcinoma. Proton-pump inhibitors represent the standard medical approach, but anti-inflammatories and antioxidants offer novel therapeutic possibilities. MATERIALS AND METHODS: Six weeks after an esophagojejunostomy reflux procedure, female Wistar rats (n = 100) were randomized to receive either an antioxidant (vitamin C, 8 mg or 28 mg/day), a cyclooxygenase-2 (COX-2) inhibitor (rofecoxib, 1 mg/day), or no therapy. After sacrifice 16 weeks later, esophageal injury was scored using pathologic and image analysis scoring. RESULTS: Esophagitis was present in all 63 animals completing the study and was severe in 27 (43%). No animal developed metaplasia or tumor. The extent of inflammation and esophageal ulceration were not significantly different between experimental groups. CONCLUSIONS: In this model of reflux injury, antioxidants and COX-2 inhibitors failed to ameliorate the severe inflammation induced. Further experimental designs should evaluate these novel approaches in less severe experimental models.

Published 18 February 2008 in J Surg Res, 145(1): 33-40.
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