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


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.
Murphy
James O
JO
Department of Surgery, St. James's Hospital and Trinity College, Dublin, Ireland.
Ravi
Narayanasamy
N
Byrne
Patrick J
PJ
McDonald
George S A
GS
Reynolds
John V
JV
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004942:Esophagitis, Peptic / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004947:Esophagus / Q000473:pathology / Q000601:surgery; D005260:Female; D007583:Jejunum / Q000601:surgery; D007783:Lactones / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013450:Sulfones / Q000627:therapeutic use
D000975:Antioxidants; D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D001205:Ascorbic Acid