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Effects of NSAIDs on cryoprobe‐induced gastric ulcer healing in rats
Author(s) -
Tibble J.,
Sigthorsson G.,
Caldwell C.,
Palmer R. H.,
Bjarnason I.
Publication year - 2001
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1046/j.1365-2036.2001.01126.x
Subject(s) - nabumetone , celecoxib , medicine , indometacin , ulcer index , gastroenterology , cyclooxygenase , prostaglandin e2 , wound healing , gastric mucosa , pharmacology , stomach , nonsteroidal , surgery , enzyme , prostaglandin endoperoxide synthase , biochemistry , chemistry
Background: Failure of ulcer healing may be critically important to the development of serious gastrointestinal complications in patients on long‐term NSAIDs. Aim: To determine the effect of indometacin, celecoxib, a cyclooxygenase‐2‐specific inhibitor, and nabumetone, a pro‐drug, on ulcer healing rates in the rat. Methods: Gastric ulcers were induced using a cryoprobe. An NSAID or a vehicle control was administered to groups of eight rats for 3 or 6 days (2 mg/kg indometacin, 9 mg/kg celecoxib or 40 mg/kg nabumetone). The ulcer area was measured and epithelial proliferation at the ulcer margins was measured histochemically. The effect of the drugs on intestinal prostaglandin levels was also assessed. Results: The mean ulcer sizes in the four groups on day 3 were comparable. On day 6, control animals and those receiving nabumetone showed significant ulcer healing ( P < 0.02), while the mean ulcer sizes in the indometacin ( P < 0.01) and celecoxib ( P < 0.02) groups were significantly larger than those in the control group. Higher doses of nabumetone (160 mg/kg), however, impaired healing. Intestinal prostaglandins were reduced ( P < 0.01) only in indometacin‐treated animals. The epithelial proliferation index was significantly lower among indometacin‐ ( P =0.02) and celecoxib‐treated ( P =0.03) animals compared to controls at day 3. Conclusions: Celecoxib and indometacin both decreased the epithelial proliferative response and delayed healing of cryoprobe‐induced gastric ulcers. In contrast, nabumetone impaired ulcer healing only at very high doses.