title: Losartan reduces trinitrobenzene sulphonic acid-induced colorectal fibrosis in rats.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Institute of Gastroenterlogy, Hadassah University Hospital, Jerusalem, Israel. dovw@ekmd.huji.ac.il
authors.forename: Dov
authors.initials: D
authors.lastname: Wengrower
authors.forename: Giuliana
authors.initials: G
authors.lastname: Zanninelli
authors.forename: Giovanni
authors.initials: G
authors.lastname: Latella
authors.forename: Stefano
authors.initials: S
authors.lastname: Necozione
authors.forename: Issa
authors.initials: I
authors.lastname: Metanes
authors.forename: Eran
authors.initials: E
authors.lastname: Israeli
authors.forename: Joseph
authors.initials: J
authors.lastname: Lysy
authors.forename: Mark
authors.initials: M
authors.lastname: Pines
authors.forename: Orit
authors.initials: O
authors.lastname: Papo
authors.forename: Eran
authors.initials: E
authors.lastname: Goldin
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D015536:Down-Regulation / Q000187:drug effects; D005355:Fibrosis; D007413:Intestinal Mucosa / Q000737:chemistry / Q000473:pathology*; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000502:physiology; D014302:Trinitrobenzenesulfonic Acid / Q000009:adverse effects
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D053773:Transforming Growth Factor beta1; D014302:Trinitrobenzenesulfonic Acid; D019808:Losartan