In this study, short-term meloxicam administration did not measurably alter the glomerular filtration rate as assessed via plasma clearance of iohexol. This suggests that renal prostaglandins in cats did not have a measurable effect on glomerular filtration rates in healthy, euvolemic, conscious states as determined on the basis of methods used in this study.
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.Animals: 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 o .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 5 .0469) or tepoxalin (P 5 .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 o .0001) or the placebo (P o .0001) groups but pyloric lesions were not significantly larger than those of the placebo group (P 5 .7829).Conclusion: 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.
Firocoxib and meloxicam administration had no effect on cyclooxygenase-1 activity, whereas tepoxalin administration resulted in inhibition of cyclooxygenase-1 and 5-lipoxygenase.
Leukotrienes are important mediators of inflammatory and allergic conditions in people and are suspected to play an important role in tumorigenesis and tumor growth of several different tumor types. Based on this, researchers are making great progress in identifying novel pharmacologic targets for several human diseases. Leukotriene inhibition has resulted in therapeutic benefit in clinical trials involving people with osteoarthritis, allergic asthma, and atopic dermatitis. Despite this progress and the possibility that leukotriene inhibition may also play an important therapeutic role in veterinary patients, parallel advances have not yet been made in veterinary medicine. This article summarizes leukotriene function and synthesis. It also reviews the published literature regarding potential therapeutic applications of leukotriene inhibition in both human and veterinary medicine, focusing primarily on osteoarthritis, NSAID induced gastrointestinal mucosal damage, allergic asthma, atopic dermatitis, and cancer.
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