Effects of melatonin on the expression of iNOS and COX-2 in rat models of colitis.
OBJECTIVE
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 28(th) day of the experiment, the rat colon mucosal damage index (CDMI) was calculated, and the colonic prostaglandin E(2) (PGE(2)), 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 PGE(2) 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 PGE(2) content, as well as the down-regulated expression of colonic iNOS and COX-2.


CONCLUSIONS
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.
Dong
Wei-Guo
WG
Department of Gastroenterology, Renmin Hospital, Wuhan University, Wuhan 430060, China. dongwg@public.wh.hb.cn
Mei
Qiao
Q
Yu
Jie-Ping
JP
Xu
Jian-Ming
JM
Xiang
Li
L
Xu
Yu
Y
D000818:Animals; D003092:Colitis / Q000201:enzymology* / Q000473:pathology; D003106:Colon / Q000201:enzymology; D051546:Cyclooxygenase 2; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000201:enzymology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008550:Melatonin / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D008550:Melatonin