Aggravation by Selective COX-1 and COX-2 Inhibitors of Dextran Sulfate Sodium (DSS)-Induced Colon Lesions in Rats

被引:0
|
作者
Mitsuaki Okayama
Shusaku Hayashi
Yoko Aoi
Hikaru Nishio
Shinichi Kato
Koji Takeuchi
机构
[1] Misasagi,Department of Pharmacology and Experimental Therapeutics Kyoto Pharmaceutical University
来源
Digestive Diseases and Sciences | 2007年 / 52卷
关键词
Dextran sulfate sodium-induced colon lesion; Nonsteroidal anti-inflammatory drug; Prostaglandin; Cyclooxygenase (COX); Selective COX-1 and COX-2 inhibitors;
D O I
暂无
中图分类号
学科分类号
摘要
We examined the effect of cyclooxygenase (COX) inhibitors on dextran sulfate sodium (DSS)-induced ulcerative colitis in rats and investigated the role of COX isozymes in the pathogenesis of this model. Experimental colitis was induced by treatment with 2.5% DSS in drinking water for 6 days. Indomethacin (a nonselective COX inhibitor), SC-560 (a selective COX-1 inhibitor), or celecoxib (a selective COX-2 inhibitor) was given PO twice daily for 6 days, during the first 3 or last 3 days of the experimental period. Daily treatment with 2.5% DSS for 6 days caused damage to the colon, with a decrease in body weight gain and colon length as well as an increase of myeloperoxidase (MPO) activity. All COX inhibitors given for 6 days significantly worsened the severity of DSS-induced colonic damage with increased MPO activity. The aggravation was also observed by SC-560 given for the first 3 days or by celecoxib given for the last 3 days. The expression of COX-2 mRNA in the colon was upregulated on day 3 during DSS treatment, with significant increase of prostaglandin E2 PGE2 production. The PGE2 content on day 3 during DSS treatment was inhibited by both indomethacin and SC-560, but not by celecoxib; on day 6 it was suppressed by both indomethacin and celecoxib, but not SC-560. These results suggest that endogenous prostaglandins (PGs) afford protection against colonic ulceration, yet the COX isozyme responsible for the production of PGs differs depending on the stage of ulceration; COX-1 in the early stage and COX-2 in the late stage.
引用
收藏
页码:2095 / 2103
页数:8
相关论文
共 50 条
  • [1] Aggravation by selective COX-1 and COX-2 inhibitors of dextran sulfate sodium (DSS) - Induced colon lesions in rats
    Okayama, Mitsuaki
    Hayashi, Shusaku
    Aoi, Yoko
    Nishio, Hikaru
    Kato, Shinichi
    Takeuchi, Koji
    DIGESTIVE DISEASES AND SCIENCES, 2007, 52 (09) : 2095 - 2103
  • [2] COX-1 and COX-2 inhibitors
    Hawkey, CJ
    BEST PRACTICE & RESEARCH CLINICAL GASTROENTEROLOGY, 2001, 15 (05) : 801 - 820
  • [3] Aggravation by selective cyclooxygenase-2 inhibitor of dextran sulfate sodium (DSS)-induced colonic lesions in rats
    Okayama, M
    Tsubouchi, R
    Rumi, G
    Kato, S
    Takeuchi, K
    GASTROENTEROLOGY, 2004, 126 (04) : A583 - A583
  • [4] THE DEVELOPMENT OF COX-1 AND COX-2 INHIBITORS: A REVIEW
    Vishwakarma, Rahul Kumar
    Negi, D. S.
    INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES AND RESEARCH, 2020, 11 (08): : 3544 - 3555
  • [5] Measurement of differential inhibition of COX-1 and COX-2 and the pharmacology of selective inhibitors
    Pairet, M
    van Ryn, J
    DRUGS OF TODAY, 1999, 35 (4-5): : 251 - 265
  • [6] COX-1 and COX-2 products in the gut: therapeutic impact of COX-2 inhibitors
    Whittle, BJR
    GUT, 2000, 47 (03) : 320 - 325
  • [7] COX-1/COX-2 inhibitors based on the methanone moiety
    Dannhardt, G
    Fiebich, BL
    Schweppenhäuser, J
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2002, 37 (02) : 147 - 161
  • [8] The pyrrole moiety as a template for COX-1/COX-2 inhibitors
    Dannhardt, G
    Kiefer, W
    Krämer, G
    Maehrlein, S
    Nowe, U
    Fiebich, B
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2000, 35 (05) : 499 - 510
  • [9] Structure of COX-1 and COX-2 enzymes and their interaction with inhibitors
    Bakhle, YS
    DRUGS OF TODAY, 1999, 35 (4-5): : 237 - 250
  • [10] Development of more selective NSAIDS: Cox-1 and Cox-2
    Barragry, T
    IRISH VETERINARY JOURNAL, 1996, 49 (09) : 553 - &