Losartan reduces trinitrobenzene sulphonic acid-induced colorectal fibrosis in rats.

"BACKGROUND: Intestinal fibrosis is a challenging clinical condition in several. fibrostenosing enteropathies, particularly Crohn's disease. Currently, no. effective preventive measures or medical therapies are available for intestinal. fibrosis. Fibrosis, due to an abnormal accumulation of extracellular matrix. proteins, is a chronic and progressive process mediated by cell⁄matrix⁄cytokine. and growth factor interactions, but may be a reversible phenomenon. Of the. several molecules regulating fibrogenesis, transforming growth factor-beta 1. (TGF-b1) appears to play a pivotal role; it is strongly induced by the local. activation of angiotensin II. The levels of both TGF-b1 and angiotensin II are. elevated in fibrostenosing Crohn's disease.. AIMS: To evaluate the in vivo effect of losartan - an angiotensin II receptor. antagonist - on the course of chronic colitis-associated fibrosis and on TGF-b1. expression.. METHODS: Colitis was induced by intrarectal instillation of trinitrobenzene. sulphonic acid (TNBS) (15 mg⁄mL) while losartan was administered orally daily by . gavage (7 mg⁄kg⁄day) for 21 days. Three groups of rats were evaluated: control. (n=10); TNBS treated (n=10); and TNBS + losartan treated (n=10). Inflammation and. fibrosis of the colon were evaluated by macro- and microscopic score analysis.. Colonic TGF-b1 levels was measured using ELISA.. RESULTS: Twenty-one days after induction, losartan significantly improved the. macro- and microscopic scores of fibrosis in the colonic wall and reduced TGF-b1 . concentration.. CONCLUSIONS: Prophylactic oral administration of losartan reduces the colorectal . fibrosis complicating the TNBS-induced chronic colitis, an effect that appears to. be mediated by a downregulation of TGF-b1 expression."