Alimentary TractNSAID-induced gastric damage in rats: Requirement for inhibition of both cyclooxygenase 1 and 2☆,☆☆,★
Section snippets
Animals
Male Wistar rats weighing 175–200 g were obtained from Charles River Breeding Farms (Montreal, Quebec, Canada) and were housed in the Animal Care Facility at the University of Calgary. The rats were fed standard laboratory chow and tap water ad libitum. The rats were deprived of food, but not water, for 18–20 hours before an experiment. All experiments described below received prior approval from the Animal Care Committee of the University of Calgary and were performed in accordance with the
Selectivity of the inhibitors
In the carrageenan-airpouch model, celecoxib inhibited PGE2 synthesis by 97% but had no effect on whole blood TX synthesis (Figure 1).
Discussion
Selective inhibition of COX-2 has been shown to be associated with significantly less gastric erosion formation than that seen with anti-inflammatory doses of conventional NSAIDs, both in animals1, 2 and humans.4, 25 Such data are consistent with the notion that the suppression of COX-1 by conventional NSAIDs underlies their ability to cause gastric damage. However, it is a presumption that blockade of COX-1 is all that is needed for erosions to develop, because before the present study, the
References (32)
- et al.
Prostaglandin synthase 1 gene disruption in mice reduces arachidonic acid-induced inflammation and indomethacin-induced gastric ulceration
Cell
(1995) - et al.
Increased expression and cellular localization of inducible nitric oxide synthase and cyclooxygenase 2 in Helicobacter pylori gastritis
Gastroenterology
(1999) - et al.
Induction of cyclooxygenase 2 in gastric mucosal lesions and its inhibition by the specific antagonist delays healing in mice
Gastroenterology
(1997) Nonsteroidal anti-inflammatory drugs and gastroenteropathy: the second hundred years
Gastroenterology
(1997)- et al.
Cyclooxygenase-1 contributes to inflammatory responses in rats and mice: implications for GI toxicity
Gastroenterology
(1998) - et al.
Role of food in gastrointestinal ulceration produced by indomethacin in the rat
Gastroenterology
(1982) - et al.
Effect of aspirin plus hydrochloric acid on the gastric mucosal microcirculation
Gastroenterology
(1987) - et al.
Focal gastric mucosal blood flow at the site of aspirin-induced ulceration
Am J Surg
(1985) - et al.
Impaired vasodilatory responses in the gastric microcirculation of cirrhotic rats
Gastroenterology
(1995) - et al.
A randomized trial comparing the effect of rofecoxib, a cyclooxygenase 2-specific inhibitor, with that of ibuprofen on the gastroduodenal mucosa of patients with osteoarthritis
Gastroenterology
(1999)
A monoclonal antibody against the CD18 leukocyte adhesion molecule prevents indomethacin-induced gastric damage in the rabbit
Gastroenterology
Modulation of leukocyte adhesion in rat mesenteric venules by aspirin and salicylate
Gastroenterology
A diclofenac derivative without ulcerogenic properties
Eur J Pharmacol
Selective inhibition of inducible cyclooxygenase 2 in vivo is antiinflammatory and nonulcerogenic
Proc Natl Acad Sci U S A
Pharmacology of a selective cyclooxygenase-2 inhibitor, L-745,337: a novel nonsteroidal anti-inflammatory agent with an ulcerogenic sparing effect in rat and nonhuman primate stomach
J Pharmacol Exp Ther
Mechanism of action of anti-inflammatory drugs
Scand J Rheumatol
Cited by (0)
- ☆
Address requests for reprints to: John L. Wallace, Ph.D., Department of Pharmacology and Therapeutics, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1 Canada. e-mail: [email protected]; fax: (403) 270-3353.
- ☆☆
Supported by a grant from the Medical Research Council of Canada (MRC) and by an MRC/AstraZeneca/Canadian Association of Gastroenterology Research Fellowship and an AHFMR Fellowship (to N.V.).
- ★
Dr. Wallace is an MRC Senior Scientist and an Alberta Heritage Foundation for Medical Research (AHFMR) Senior Scientist.