Effects of NSAIDs on cryoprobe-induced gastric ulcer healing in rats.
BACKGROUND
Failure of ulcer healing may be critically important to the development of serious gastrointestinal complications in patients on long-term NSAIDs.


OBJECTIVE
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.
Tibble
J
J
Department of Medicine, Guy's, King's and St Thomas' Medical School, London, UK.
Sigthorsson
G
G
Caldwell
C
C
Palmer
R H
RH
Bjarnason
I
I
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002074:Butanones / Q000494:pharmacology; D000068579:Celecoxib; D002455:Cell Division / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D000077430:Nabumetone; D011453:Prostaglandins / Q000378:metabolism; D011720:Pyrazoles; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D013449:Sulfonamides / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002074:Butanones; D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib; D000077430:Nabumetone; D007213:Indomethacin