Gastric effects of the selective cyclooxygenase-2 inhibitor, celecoxib, in the rat.
BACKGROUND
Recent studies have revealed that cyclooxygenase-2 is involved in the protection of the damaged gastric mucosa, mediating, in particular, the acceleration of ulcer healing and angiogenesis; therein, it has been suggested that selective cyclooxygenase-2 inhibitors, although safe in healthy stomach, may have deleterious effects on the injured gastric mucosa. Moreover, no information is available about direct effects of these drugs on gastric surface epithelium.


OBJECTIVE
To investigate the gastric effects of the selective cyclooxygenase-2 inhibitor, celecoxib, in healthy and damaged rat gastric mucosa.


METHODS
Gastric toxicity was studied in the rat by measuring gastric potential difference and mucosal lesions. Celecoxib was administered intragastrically, either in basal conditions or in combination with damaging (acetylsalicylic acid and ethanol) or protective (sodium nitroprusside and lipopolysaccharides from Escherichia coli) agents. The anti-inflammatory activity was evaluated in the carrageenan-induced paw oedema assay. The non-selective inhibitors indomethacin and acetylsalicylic acid were used for comparison.


RESULTS
In conscious rats celecoxib, indomethacin and acetylsalicylic acid significantly reduced the paw oedema induced by carrageenan. While acetylsalicylic acid and indomethacin significantly reduced basal gastric potential difference and caused gastric mucosal lesions, celecoxib was ineffective; moreover, it did not aggravate the direct damaging effect of intragastric ethanol or aspirin. Pretreatment with the non-selective nitric oxide synthase inhibitor N-nitro-L-argynine methyl ester did not significantly change the gastric effects of celecoxib. Both celecoxib and indomethacin prevented the gastroprotective effects induced by sodium nitroprusside (nitric oxide donor) or by bacterial lipopolysaccharides (inducer of nitric oxide synthesis). CONCLUSIONS. These data indicate that the selective cyclooxygenase-2 inhibitor celecoxib did not alter gastric mucosal barrier nor induced mucosal lesions in the healthy or nitric oxide-deficient rat gastric mucosa. However, cyclooxygenase-2 inhibition impaired nitric oxide-dependent gastroprotection, indicating that cyclooxygenase-2 derived prostaglandins may be involved in the gastric mucosal defence.
Coppelli
G
G
Pharmacology Section, Department of Human Anatomy, Pharmacology and Forensic Medicine, Medical Faculty, University of Parma, Via Volturno, 39, 43100 Parma, Italy.
Guaita
E
E
Spaggiari
S
S
Coruzzi
G
G
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D002351:Carrageenan; D000068579:Celecoxib; D003243:Consciousness; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D011720:Pyrazoles; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D002351:Carrageenan; D000068579:Celecoxib; D001241:Aspirin; D007213:Indomethacin