title: Angiotensin II type 1 receptor blocker inhibits fibrosis in rat nonalcoholic steatohepatitis.
abstract: Nonalcoholic steatohepatitis (NASH) is now the most frequent cause of chronic liver impairment in developed countries and is a suggested causative factor in the development of cryptogenic cirrhosis and hepatocellular carcinoma. At present there is no effective and accepted therapy for NASH. The renin-angiotensin system is involved in hepatic fibrosis through activation of hepatic stellate cells, major fibrogenic cells in the liver. Hepatic stellate cells are activated by liver injury to express excessive matrix proteins and profibrogenic cytokines such as transforming growth factor-beta 1. Medicines that inhibit this pathway may be of therapeutic potential in NASH. Using a methionine-choline-deficient rat model of NASH, we studied the potential utility of an angiotensin II type 1 receptor blocker (ARB), olmesartan, on biochemical, histologic, and antioxidant measures of disease activity. ARB significantly attenuated increases in aspartate aminotransferase, activation of hepatic stellate cells, oxidative stress, expression of transforming growth factor-beta 1, expression of collagen genes, and liver fibrosis.
  
  
  CONCLUSIONS
  Our observations strongly suggest a potential preventive role for ARB in the progression of nonalcoholic steatohepatitis.
authors.affiliation: Department of Gastroenterology and Hepatology, Kochi Medical School, Nankoku, Kochi 783-8505, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Hirose
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ono
authors.forename: Toshiji
authors.initials: T
authors.lastname: Saibara
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Nozaki
authors.forename: Kosei
authors.initials: K
authors.lastname: Masuda
authors.forename: Akemi
authors.initials: A
authors.lastname: Yoshioka
authors.forename: Masaya
authors.initials: M
authors.lastname: Takahashi
authors.forename: Naoaki
authors.initials: N
authors.lastname: Akisawa
authors.forename: Shinji
authors.initials: S
authors.lastname: Iwasaki
authors.forename: Jude A
authors.initials: JA
authors.lastname: Oben
authors.forename: Saburo
authors.initials: S
authors.lastname: Onishi
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000821:Animal Feed; D000818:Animals; D002794:Choline / Q000494:pharmacology; D055513:Connective Tissue Growth Factor; D005234:Fatty Liver / Q000188:drug therapy* / Q000473:pathology; D007093:Imidazoles / Q000494:pharmacology*; D017874:Immediate-Early Proteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008715:Methionine / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; C526316:CCN2 protein, rat; D007093:Imidazoles; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D055513:Connective Tissue Growth Factor; C437965:olmesartan; D008715:Methionine; D002794:Choline