A nitric oxide-releasing nonsteroidal anti-inflammatory drug accelerates gastric ulcer healing in rats.
OBJECTIVE
Nonsteroidal anti-inflammatory drugs (NSAIDs) have well-characterized inhibitory effects on gastric ulcer healing. A new class of gastrointestinal-sparing, nitric oxide-releasing NSAID derivatives has been recently described. This study was performed to determine if one of these compounds (nitrofenac) would influence healing of a preexisting ulcer.


METHODS
Seven days after induction of gastric ulcer with serosal acetic acid, daily oral treatment with antiinflammatory doses of diclofenac, nitrofenac, or vehicle was started. After 7 days of treatment, the ulcer area was measured. The effects of misoprostol and two drugs that show in vitro selectivity for inhibiting cyclooxygenase 2 (nabumetone and L745,337) were also assessed.


RESULTS
Diclofenac, nabumetone, and L745,337 had no effect on ulcer healing when compared with vehicle. Only diclofenac significantly decreased hematocrit and weight gain. On the other hand, nitrofenac significantly accelerated healing. Glyceryl trinitrate also significantly and dose dependently accelerated healing. Nitrofenac suppressed cyclooxygenase 1 activity to a similar extent as diclofenac.


CONCLUSIONS
These results show that an NO-releasing NSAID derivative and an NO donor could accelerate ulcer healing, whereas a standard NSAID, misoprostol, and two inhibitors of cyclooxygenase 2 had no effect. In addition to sparing the gastrointestinal tract, NO-releasing NSAIDs, despite suppressing cyclooxygenase activity, are capable of accelerating tissue repair.
Elliott
S N
SN
Intestinal Disease Research Unit, University of Calgary, Alberta, Canada.
McKnight
W
W
Cirino
G
G
Wallace
J L
JL
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D004008:Diclofenac / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005744:Gastric Acid / Q000378:metabolism; D006400:Hematocrit; D008297:Male; D016595:Misoprostol / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013929:Thromboxane B2 / Q000096:biosynthesis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D016595:Misoprostol; D004008:Diclofenac; C087608:nitrofenac; D013929:Thromboxane B2