Cyclooxygenase expression and prostanoid production in pyloric and duodenal mucosae in dogs after administration of nonsteroidal anti-inflammatory drugs.
OBJECTIVE
To assess cyclooxygenase (COX) expression and prostanoid concentrations in pyloric and duodenal mucosae of dogs after administration of nonsteroidal anti-inflammatory drugs (NSAIDs).


METHODS
8 healthy dogs.


METHODS
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
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.
Wooten
Jenna G
JG
Gastrointestinal Biology Research Laboratory, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
Blikslager
Anthony T
AT
Ryan
Kathleen A
KA
Marks
Steve L
SL
Law
J Mac
JM
Lascelles
B Duncan X
BD
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001706:Biopsy / Q000662:veterinary; D015153:Blotting, Western / Q000662:veterinary; D018592:Cross-Over Studies; D051545:Cyclooxygenase 1 / Q000096:biosynthesis*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D004285:Dogs / Q000378:metabolism*; D004724:Endoscopy / Q000662:veterinary; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006651:Histocytochemistry / Q000662:veterinary; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis*; D011706:Pyloric Antrum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D011897:Random Allocation; D013929:Thromboxane B2 / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011453:Prostaglandins; D013929:Thromboxane B2; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2