Original Paper

Healing Impairment Effect of Cyclooxygenase Inhibitors on Dextran Sulfate Sodium-Induced Colitis in Rats
Ryoichi Tsubouchi, Shusaku Hayashi, Yoko Aoi, Hikaru Nishio, Shun Terashima, Shinichi Kato, Koji Takeuchi

Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Kyoto, Japan

Address of Corresponding Author

Digestion 2006;74:91-100 (DOI: 10.1159/000097657)

  Key Words

• Colitis healing impairment effect
• COX inhibitors
• Cyclooxygenase-1
• Cyclooxygenase-2
• Dextran sulfate sodium
• Inflammatory bowel disease

  Abstract

We examined the effects of various cyclooxygenase (COX) inhibitors on the healing of colonic lesions induced by dextran sulfate sodium (DSS) in the rat. Colonic lesions were induced by 2.5% DSS in the drinking water for 7 days, and then the animals were fed with tap water for subsequent 7 days. Indomethacin (a nonselective COX inhibitor), SC-560 (a selective COX-1 inhibitor), or rofecoxib (a selective COX-2 inhibitor) was given orally twice daily after termination of the DSS treatment. DSS treatment caused severe colonic lesions with a decrease in body weight gain and colon length as well as an increase in myeloperoxidase activity and thiobarbituric acid reactant levels. The severity of colitis gradually reduced, with an improvement of morphological and histological alterations. Daily administration of indomethacin and rofecoxib significantly delayed the healing of colitis with deleterious influences on histological restitution as well as mucosal inflammation, while SC-560 had no effect. Although COX-1 mRNA was expressed in the colon without much alteration during the test period, the expression of COX-2 was upregulated with a peak on day 3 and decreased thereafter. The mucosal prostaglandin E₂ content in the colon showed a biphasic change, in parallel with that of the COX-2 expression. The increased prostaglandin E₂ production in the injured mucosa was attenuated by indomethacin and rofecoxib, but not by SC-560. These results suggest that endogenous prostaglandins produced by COX-2 play an important role in the healing of DSS-induced colonic lesions. Caution should be paid to the use of selective COX-2 inhibitors as well as nonsteroidal anti-inflammatory drugs in patients with colitis.

Copyright © 2006 S. Karger AG, Basel

  Author Contacts

Shinichi Kato, PhD
Department of Pharmacology and Experimental Therapeutics
Kyoto Pharmaceutical University, Misasagi, Yamashina
Kyoto 607-8414 (Japan)
Tel. +81 75 595 4680, Fax +81 75 595 4774, E-Mail skato@mb.kyoto-phu.ac.jp

  Article Information

Received: August 7, 2006
Accepted: October 6, 2006
Published online: December 1, 2006
Number of Print Pages : 10
Number of Figures : 9, Number of Tables : 0, Number of References : 43