Protective effect of ilomastat on trinitrobenzenesulfonic acid-induced ulcerative colitis in rats

World J Gastroenterol. 2008 Oct 7;14(37):5683-8. doi: 10.3748/wjg.14.5683.

Abstract

Aim: 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).

Conclusion: Ilomastat improves TNB-induced UC in rats by inhibiting the MMP-1 activity.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Colitis, Ulcerative / chemically induced
  • Colitis, Ulcerative / enzymology
  • Colitis, Ulcerative / prevention & control*
  • Colon / drug effects*
  • Colon / enzymology
  • Colon / pathology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Gastrointestinal Agents / pharmacology*
  • Hydroxamic Acids
  • Immunohistochemistry
  • Indoles / pharmacology*
  • Male
  • Matrix Metalloproteinase 1 / genetics
  • Matrix Metalloproteinase 1 / metabolism
  • Matrix Metalloproteinase Inhibitors*
  • Protease Inhibitors / pharmacology*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Trinitrobenzenesulfonic Acid

Substances

  • Anti-Inflammatory Agents
  • Gastrointestinal Agents
  • Hydroxamic Acids
  • Indoles
  • Matrix Metalloproteinase Inhibitors
  • Protease Inhibitors
  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinase-1
  • Trinitrobenzenesulfonic Acid
  • Matrix Metalloproteinase 1
  • ilomastat