Assesment of inflammation and early fibrosis markers on colonic mucosa and effects of colchicine on them in an exprimental colitis model

Ulcerative colitis and Crohn?s diseases are relapsing chronic inflammatory conditions resulted by uncontrolled immune response againist intestinal bacteria.Aminosalycilates, corticosteroids, immunsupressive and biological drugs are the most widely used agents in treatment of IBDs. Despite all these agents, there is stil no effective treatment which can induce long lasting remission and prevent relapses and fibrotic complications that may occur during the course of the disease.Fibrosis is one of the major complications of IBDs. During the process of fibrosis cells, extracellular matrix, cytokines and growth factors all play important roles. TGFß is the most important growth factor among all.This molecule can induce cell proliferation, collogen and ? SMA synthesis and helps epithelial cells to transform into mesenchymal cells which are capable of producing ECM.MMP 3 is a member of metalloproteinase family and responsible from tissue damage in IBDs. This enzyme is induced by cytokines during inflammation and degrade collogen in ECM causing mucosal ulceration and complications such as fistula formation. Tissue inhibitors of metalloproteinases (TIMPs) are regulator molecules which can antogonize and neutralize the action of MMPs, slows down tisssue degradation and starts wound healing. TIMP 1 is related with severity of the disease, development of fibrotic complications and even carcinogenesis in IBDs. Clolchicine is a well known drug with anti inflammatory and anti fibrotic effects.Our purpose in this study was determining the tissue levels of MMP3, TIMP1 and TGFß in the colonic tissues and demonstrate the effects of colchicine on these molecules at a very early stage of experimental ulcerative colitis model in rats.We have used 60 Wistar albino rats in our study. Six different groups were made and there were 10 rats in each group. Colitis was induced by rectal acetic acid in 4 groups. Colchicine was given to rats via po or iv route in the two colitis groups. All rats were decapitated on the 5th day and their distal colons were extracted to be examined. In addition to that, tissue levels of MMP3, TIMP1 and TGF ß were determined imunohistochemically by an experienced pathologist. All the colitis groups were compared with each other and two control groups according to the tissue levels of these three molecules.Macroscopic and microscopic appearance of colon were significiantly different in colitis groups than the control groups.There were severe mucosal damage, ulcerations, goblet cell loss and increment in muscular layer and wall thickness of colon samples in colitis groups when compared to control groups.Colchicine did not cause any histopathological difference between colitis groups.MMP3, TIMP1 and TGFß levels were significiantly supressed in colitis groups received colchicine compared to the control groups and the other colitis groups which didn?t receive colchicine.These results made us think that colchicine might reduce the severity of inflammation and frequency of fibrotic complications by supressing MMP3, TIMP1 and TGFß tissue levels if it is added to conventional treatment regimens in IBDs.