Effects of firocoxib and tepoxalin on healing in a canine gastric mucosal injury model.
BACKGROUND
Little is known about the effect of dual cyclooxygenase (COX) and lipoxygenase inhibition on canine gastric mucosal healing.


OBJECTIVE
This study compares the effects of putative dual COX and 5-lipoxygenase inhibition with that of COX-2 selective inhibition on gastric mucosal lesion healing in dogs.


METHODS
Six normal adult mixed-breed research dogs.


METHODS
Gastric body and pyloric lesions were induced by endoscopic biopsy. Dogs were treated with tepoxalin, firocoxib, or placebo for 7 days in a randomized 3-way crossover study design. Healing was evaluated on days 2, 4, and 7 of treatment by endoscopic lesion scoring. Eicosanoid concentrations in plasma and at the lesion margins were determined on days 2, 4, and 7. Repeated measures analyses were performed. All hypothesis tests were 2-sided with P < .05. Multiple comparisons were adjusted using Tukey's test.


RESULTS
Significant treatment differences were noted in the pyloric lesion area measurements. Overall, the firocoxib group had larger lesions than the placebo (P= .0469) or tepoxalin (P= .0089) groups. Despite larger pyloric lesions in the firocoxib group, mucosal prostaglandin production did not differ significantly from placebo. In contrast, the tepoxalin group had significantly lower pyloric mucosal prostaglandin production compared with the firocoxib (P < .0001) or the placebo (P < .0001) groups but pyloric lesions were not significantly larger than those of the placebo group (P= .7829).


CONCLUSIONS
COX-2 inhibition by firocoxib slowed wound healing by a mechanism independent of prostaglandin synthesis. Suppression of mucosal prostaglandin production by tepoxalin did not alter mucosal lesion healing compared with placebo.
Goodman
L
L
University of Georgia College of Veterinary Medicine, Athens, GA, USA. lgoodman@uga.edu
Torres
B
B
Punke
J
J
Reynolds
L
L
Speas
A
A
Ellis
A
A
Budsberg
S
S
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000527:Alprostadil / Q000096:biosynthesis; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001706:Biopsy; D018592:Cross-Over Studies; D015232:Dinoprostone / Q000096:biosynthesis / Q000097:blood; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D011720:Pyrazoles / Q000627:therapeutic use*; D013272:Stomach Diseases / Q000139:chemically induced / Q000188:drug therapy / Q000662:veterinary*; D013450:Sulfones / Q000627:therapeutic use*; D013929:Thromboxane B2 / Q000097:blood; D014945:Wound Healing / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011720:Pyrazoles; D013450:Sulfones; D013929:Thromboxane B2; D000527:Alprostadil; D015232:Dinoprostone; D015107:4-Butyrolactone; C073135:tepoxalin; C487384:firocoxib