ISSN:
1573-2568
Keywords:
CYCLOOXYGENASE-2 INHIBITORS
;
NONSTEROIDAL ANTIINFLAMMATORY DRUGS
;
ASPIRIN
;
GASTRIC ULCER
;
ULCER HEALING
;
ANTIINFLAMMATORY ACTION
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Effects of selective cyclooxygenase-2 (COX-2)inhibitors (NS-398) and nitric oxide (NO)-releasingaspirin (NO-ASA) on gastric ulcerogenic and healingresponses were examined in comparison with nonselective COX inhibitors such as indomethacin and aspirin(ASA). Hypothermic stress (28-30°C, 4 hr) inducedgastric lesions in anesthetized rats with an increase ofacid secretion. The lesions induced by hypothermic stress were markedly worsened by subcutaneousadministration of both indomethacin and ASA but were notaffected by either NS-398 or NO-ASA, although theincreased acid secretion during hypothermia was not affected by any of the drugs. On the otherhand, the healing of gastric ulcers induced in mice bythermal cauterization (70°C, 15 sec) wassignificantly delayed by daily subcutaneousadministration of indomethacin and ASA as well as NS-398, but not by NO-ASA.COX-2 mRNA was not detected in the intact mucosa but waspositively expressed in the ulcerated mucosa, mostpotently on day 3 after ulceration. Prostaglandin contents in the intact mouse stomach werereduced by indomethacin, ASA, and NO-ASA, while theincreased prostaglandin generation in the ulceratedmucosa was inhibited by all drugs including NS-398.After subcutaneous administration of NO-ASA topylorus-ligated rats and mice, high amounts ofNOx were detected in both the gastriccontents and serum. In addition, both NS-398 and NO-ASAshowed an equipotent antiinflammatory effect againstcarrageenan-induced paw edema in rats as compared withindomethacin and ASA. These results suggest that bothindomethacin and ASA not only increased the mucosalulcerogenic response to stress but impaired the healingresponse of gastric ulcers as well. The former actionwas due to inhibition of COX-1, while the latter effectwas accounted for by inhibition of COX-2 and was mimicked by the COX-2-selective inhibitorNS-398. NO-ASA, although it inhibited both COX-1 andCOX-2 activity, had no deleterious effects on gastriculcerogenic and healing responses.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1018846912032
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