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Effects of NSAIDs on cryoprobe-induced gastric ulcer healing in rats.

AbstractBACKGROUND:
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.
AuthorsJ Tibble, G Sigthorsson, C Caldwell, R H Palmer, I Bjarnason
JournalAlimentary pharmacology & therapeutics (Aliment Pharmacol Ther) Vol. 15 Issue 12 Pg. 2001-8 (Dec 2001) ISSN: 0269-2813 [Print] England
PMID11736732 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Inflammatory Agents, Non-Steroidal
  • Butanones
  • Cyclooxygenase Inhibitors
  • Prostaglandins
  • Pyrazoles
  • Sulfonamides
  • Celecoxib
  • Nabumetone
  • Indomethacin
Topics
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
  • Butanones (pharmacology)
  • Celecoxib
  • Cell Division (drug effects)
  • Cyclooxygenase Inhibitors (pharmacology)
  • Epithelial Cells (drug effects)
  • Gastric Mucosa (drug effects, pathology)
  • Indomethacin (pharmacology)
  • Male
  • Nabumetone
  • Prostaglandins (metabolism)
  • Pyrazoles
  • Rats
  • Rats, Sprague-Dawley
  • Stomach Ulcer (chemically induced, drug therapy, physiopathology)
  • Sulfonamides (pharmacology)
  • Wound Healing (drug effects)

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