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Effect of losartan on early liver fibrosis development in a rat model of nonalcoholic steatohepatitis
Author(s) -
Ibañez Patricio,
Solis Nancy,
Pizarro Margarita,
Aguayo Gloria,
Duarte Ignacio,
Miquel Juan Francisco,
Accatino Luigi,
Arrese Marco
Publication year - 2007
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2006.04700.x
Subject(s) - losartan , medicine , cirrhosis , fibrosis , endocrinology , hydroxyproline , steatohepatitis , liver injury , creatinine , liver biopsy , hepatic stellate cell , cholestasis , fatty liver , angiotensin ii , receptor , biopsy , disease
Background and Aim: Nonalcoholic steatohepatitis (NASH) is a metabolic disorder of the liver that may evolve into fibrosis or cirrhosis. Recent studies have shown reduction of experimental liver fibrosis with the use of angiotensin‐converting‐enzyme inhibitors or angiotensin‐receptor antagonists. The aim of this study was to determine whether losartan can influence the early phase of fibrogenesis in an animal model of NASH. Methods: To induce NASH, a choline‐deficient diet (CDD) was given to Sprague‐Dawley rats for 12 weeks. These animals were then compared with a control group receiving choline‐supplemented diet (CSD) and a group fed a CDD plus losartan (10 mg/kg/day). Biochemical (serum levels of alanine aminotransferase and aspartate aminotransferase) and histological evaluation of fatty liver was performed by conventional techniques. Hydroxyproline content in liver tissue was assayed by spectrophotometry. In addition, mRNA levels of procollagen I and transforming growth factor (TGF)‐β were assessed by semiquantitative RT‐PCR and stellate cell activation by α‐actin immunofluorescence stain. Results: After 12 weeks CDD induced a marked elevation of serum aminotranferases, a severe fatty liver infiltration with mild histological inflammation and fibrosis. These findings correlated with a significant increase in mRNA levels of both procollagen I and TGF‐β and significant increased liver hydroxyproline content. No differences were seen between rats receiving CDD alone and rats receiving CDD plus losartan with regard to the biochemical, morphological or molecular alterations induced by the CDD. Conclusion: Losartan does not seem to influence liver injury and fibrogenic events in the CDD model of NASH.