Protective effect of ilomastat on trinitrobenzenesulfonic acid-induced ulcerative colitis in rats.
OBJECTIVE
To evaluate the protective effects of ilomastat, an exogenous matrix metalloproteinase (MMP) inhibitor, on trinitrobenzenesulfonic acid (TNB)-induced ulcerative colitis (UC) in rats.


METHODS
Male SD rats were randomly divided into model group, protective groups A and B, and normal control group. Rats in the model group received only intra-colonic TNB. Rats in the protective groups A and B received intra-peritoneal ilomastat of 10 mg/kg and 20 mg/kg, respectively, beside TNB. Rats in the normal control group received only intra-colonic normal saline. After 3 wk, segments of colon were obtained. RT-PCR and immunohistochemistry were used to examine the expression of MMP-1 and TIMP-1. Hematoxylin-eosin (HE) staining was used for pathological study.


RESULTS
The model of UC was successfully induced in rats. Inflammation of colonic mucosa greatly improved in protective groups A and B. Expression of MMP-1 and TIMP-1 in the model group, protective groups A and B was significantly higher than that in the normal control group (P < 0.0001) with MMP-1 expression increased more significantly than TIMP-1 expression. Expression of MMP-1 in protective groups A and B was significantly lower than that in the model group (P < 0.0001) . Expression of MMP-1 in protective group B was significantly lower than that in protective group A (P < 0.0001).


CONCLUSIONS
Ilomastat improves TNB-induced UC in rats by inhibiting the MMP-1 activity.
Department of Gastroenterology, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, China. albertwyd@yahoo.com.cn
Ying-De
YD
Wang
Wei
W
Wang
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D006877:Hydroxamic Acids; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid
D000893:Anti-Inflammatory Agents; D005765:Gastrointestinal Agents; D006877:Hydroxamic Acids; D007211:Indoles; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D014302:Trinitrobenzenesulfonic Acid; D020781:Matrix Metalloproteinase 1; C119203:ilomastat