Objective—To assess cyclooxygenase (COX) expression and prostanoid concentrations in pyloric and duodenal mucosae of dogs after administration of nonsteroidal anti-inflammatory drugs (NSAIDs).
Animals—8 healthy dogs.
Procedures—Each dog received carprofen (4.4 mg/kg, q 24 h), deracoxib (2 mg/kg, q 24 h), aspirin (10 mg/kg, q 12 h), and placebo (1 dog treat, q 24 h) orally for 3 days (4-week interval between treatments). Before study commencement (baseline) and on day 3 of each treatment, pyloric and duodenal mucosal appearance was assessed endoscopically and biopsy specimens were obtained for histologic examination. Cyclooxygenase-1 and COX-2 protein expressions were assessed via western blotting, and prostanoid concentrations were measured via ELISAs. An ANOVA was used to analyze data.
Results—Treatments had no effect on mucosal appearance and ulceration was not evident histologically. In pyloric and duodenal mucosae, COX-1 expression was unaffected by treatments. Cyclooxygenase-2 expression remained unchanged in pyloric mucosa; in duodenal mucosa, aspirin significantly increased COX-2 expression, compared with effects of deracoxib and carprofen. At baseline, total prostaglandin and thromboxane B2 concentrations in pyloric mucosa were significantly greater than those in duodenal mucosa. Aspirin significantly decreased both prostanoid concentrations in both mucosal tissues, compared with other treatments. In pyloric mucosa, carprofen administration significantly decreased total prostaglandin and thromboxane B2 concentrations, compared with deracoxib administration.
Conclusions and Clinical Relevance—In dogs, prostanoid synthesis was greater in pyloric mucosa than it was in duodenal mucosa. Nonselective NSAIDs significantly decreased prostanoid concentrations in these mucosae, compared with the effects of a selective COX-2 NSAID.
Objective—To assess in vivo effects of short-term administration of NSAIDs with varied cyclooxygenase (COX)-2 selectivity on pyloric and duodenal mucosa.
Animals—8 healthy dogs.
Procedures—Each dog received deracoxib (2 mg/kg, PO, q 24 h for 3 days), firocoxib (5 mg/kg, PO, q 24 h for 3 days), meloxicam (0.2 mg/kg, PO, q 24 h for 1 day followed by 0.1 mg/kg, PO, q 24 h for 2 days), or placebo orally for 3 days; there was a 4-week interval between successive treatments. Prior to and on day 3 of drug administration, pyloric and duodenal mucosae were assessed endoscopically and biopsy specimens obtained for histologic examination. Cyclooxygenase-1 and -2 protein expressions were assessed (western blotting) and prostanoid concentrations measured (ELISAs). Data were analyzed by use of an ANOVA.
Results—Drug administration did not significantly affect endoscopic mucosal scores, histologic scores, or COX-1 or -2 protein expression. The COX-1 protein expression was significantly higher in the pylorus than in the duodenum. Total prostaglandin and thromboxane B2 (TXB2) concentrations were significantly greater in pyloric than in duodenal mucosa. Drug administration had no effect on prostaglandin or TXB2 concentrations.
Conclusions and Clinical Relevance—Prostanoid concentrations in gastric and duodenal tissues, and gross and histologic appearances, were not significantly affected by drugs with varied COX-2 selectivity. These findings suggested that, for these experimental conditions, there were no differences among the preferential and selective COX-2 inhibitors with regard to adverse effects on the gastric and duodenal portions of the gastrointestinal tract of dogs.
Objective—To determine whether clinically normal dogs have lesions in the pylorus and duodenum and to examine the expression of cyclooxygenase (COX) isoforms in the pylorus and duodenum of these dogs.
Animals—27 clinically normal dogs.
Procedures—Physical examination was performed on clinically normal dogs from animal shelters and research projects; the dogs were then euthanized. After the dogs were euthanized, the pylorus and duodenum were photographed and scored for gross appearance of lesions. Samples were obtained for histologic evaluation and determination of COX expression via western blot analyses. Tissues from the pylorus and duodenum were categorized as normal, inflamed, or eroded on the basis of histologic analysis. Each histologic category of tissue was then evaluated to determine the correlation with gross appearance and COX expression.
Results—Of the 27 dogs, 5 had unremarkable histologic findings in the pylorus and duodenum. Inflammation was found in the pylorus of 10 dogs and in the duodenum of 5 dogs. Epithelial erosion was detected in the pylorus of 1 dog and in the duodenum of 3 dogs. Gross appearance was not significantly correlated with histologic appearance. Expression of COX-1 was not upregulated by inflammation, whereas COX-2 expression was increased by inflammation or erosion.
Conclusions and Clinical Relevance—Dogs that appear to be clinically normal may have underlying gastroduodenal lesions associated with upregulation of COX-2. Because of the inability to determine this during routine physical examination, practitioners should be aware of this potential situation when prescribing COX inhibitors.