Effect of losartan on early liver fibrosis development in a rat model of nonalcoholic steatohepatitis

• Published in: Journal of gastroenterology and hepatology Vol. 22; no. 6; pp. 846 - 851
• Main Authors: Ibañez, Patricio, Solis, Nancy, Pizarro, Margarita, Aguayo, Gloria, Duarte, Ignacio, Miquel, Juan Francisco, Accatino, Luigi, Arrese, Marco
• Format: Journal Article
• Language: English
• Published: Melbourne, Australia Blackwell Publishing Asia 01.06.2007; Blackwell Science
• Subjects: Angiotensin II Type 1 Receptor Blockers - pharmacology; Animals; Biological and medical sciences; Choline Deficiency; Disease Models, Animal; Fatty Liver - complications; Fatty Liver - drug therapy; Gastroenterology. Liver. Pancreas. Abdomen; hepatic fibrosis; Hydroxyproline - metabolism; Liver Cirrhosis - etiology; Liver Cirrhosis - prevention & control; Liver Function Tests; Liver. Biliary tract. Portal circulation. Exocrine pancreas; losartan; Losartan - pharmacology; Male; Medical sciences; Other diseases. Semiology; Rats; Rats, Sprague-Dawley; renin-angiotensin system; Reverse Transcriptase Polymerase Chain Reaction; steatohepatitis; transforming growth factor-β; Choleretic; Tetrazole derivatives; Rat; Transforming growth factor β; Hepatoprotector; Peptide hormone; Non peptide compound; Hepatic disease; Octapeptide; Fatty liver; Losartan; Angiotensin II; Reverse transcription polymerase chain reaction; Hepatic fibrosis; steatohepatitis; Alanine; Rodentia; AT1 angiotensin receptor; Cirrhosis; Vertebrata; Renin angiotensin system; Metabolic disorder; Mammalia; Biphenyl derivatives; transforming growth factor-β; Aminoacid; Animal; Choline; Non alcoholic steatohepatitis; Digestive diseases; Antihypertensive agent; Models; Angiotensin antagonist; Molecular biology; Immunofluorescence; Spectrophotometry; renin-angiotensin system
• ISSN: 0815-9319; 1440-1746
• DOI: 10.1111/j.1440-1746.2006.04700.x

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.