Basic Research
Copyright ©The Author(s) 2003. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 15, 2003; 9(6): 1307-1311
Published online Jun 15, 2003. doi: 10.3748/wjg.v9.i6.1307
Effects of melatonin on the expression of iNOS and COX-2 in rat models of colitis
Wei-Guo Dong, Qiao Mei, Jie-Ping Yu, Jian-Ming Xu, Li Xiang, Yu Xu
Wei-Guo Dong, Jie-Ping Yu, Yu Xu, Department of Gastroenterology, Renmin Hospital, Wuhan University, Wuhan 430060, Hubei Province, China
Qiao Mei, Jian-Ming Xu, Li Xiang, Department of Gastroenterology, the First Affiliated Hospital, Anhui Medical University, Hefei 230032, Anhui Province, China
Author contributions: All authors contributed equally to the work.
Correspondence to: Wei-Guo Dong, Department of Gastroenterology, Renmin Hospital, Wuhan University, Wuhan 430060, China. dongwg@public.wh.hb.cn
Telephone: +86-27-88041911 Ext 7737
Received: November 26, 2002
Revised: January 4, 2003
Accepted: January 13, 2003
Published online: June 15, 2003
Abstract

AIM: To investigate the effects of melatonin (MT) on the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in rat models of colitis.

METHODS: Healthy adult Sprague-Dawlay (SD) rats of both sexes, weighing 280 ± 30 g, were employed in the present study. The rat models of colitis were induced by either acetic acid or 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) enemas. The experimental animals were randomly divided into melatonin treatment and model control group that were intracolicly treated daily with melatonin at doses of 2.5, 5.0, 10.0 mg•kg-1 and equal amount of saline respectively from 24 h following induction of colitis in rats inflicted with acetic acid enema and the seventh day in rats with TNBS to the end of study. A normal control group of rats treated with neither acetic acid nor TNBS but saline enema was also included in the study. On the 28th day of the experiment, the rat colon mucosal damage index (CDMI) was calculated, and the colonic prostaglandin E2 (PGE2), nitric oxide (NO), as well as the iNOS and COX-2 expression were also determined biochemically or immunohistochemically.

RESULTS: CDMI increased to 2.87 ± 0.64 and 3.12 ± 1.12 respectively in rats treated with acetic acid and TNBS enema, which was in accordance with the significantly elevated colonic NO and PGE2 contents, as well as the up-regulated colonic iNOS and COX-2 expression in both of the two rat models of colitis. With treatment by melatonin at the doses of 5.0 and 10.0 mg•kg-1, CDMI in both models of rat colitis was significantly decreased (P < 0.05-0.01), which accorded synchronously and unanimously with the reduced colonic NO and PGE2 content, as well as the down-regulated expression of colonic iNOS and COX-2.

CONCLUSION: Melatonin has a protective effect on colonic injury induced by both acetic acid and TNBS enemas, which is probably via a mechanism of local inhibition of iNOS and COX-2 expression in colonic mucosa.

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