title: Angiotensin II type 1 receptor antagonist prevents hepatic carcinoma in rats with nonalcoholic steatohepatitis.
abstract: BACKGROUND
  Angiotensin II type 1 receptor blockers (ARBs) have been reported to attenuate hepatic fibrosis in non-alcoholic steatohepatitis (NASH). However, it is uncertain whether ARBs prevent hepatocarcinogenesis in NASH even after hepatic fibrosis has developed.
  
  
  METHODS
  Male Wistar rats were fed with a choline-deficient, L-amino acid-defined (CDAA) diet for 24 weeks, and then fed with the CDAA diet with telmisartan (2 mg/kg/day), a novel ARB, or vehicle for another 24 weeks. The liver histology and the expression of genes and proteins related to angiogenesis were investigated.
  
  
  RESULTS
  The 24-week CDAA diet induced liver cirrhosis. The 48-week CDAA diet exacerbated liver cirrhosis, and developed hepatocellular carcinoma (HCC) in 54.6 % of the rats concurrently with increases of hypoxia-inducible factor-1α (HIF-1α) protein and vascular endothelial growth factor (VEGF) mRNA, which are potent angiogenic factors in the liver. Telmisartan inhibited hepatic fibrosis and preneoplastic lesions and prevented the development of HCC along with inducing decreases in HIF-1α protein and VEGF mRNA.
  
  
  CONCLUSIONS
  These data indicated that telmisartan may prevent hepatocarcinogenesis through the inhibition of hepatic angiogenesis even after liver cirrhosis has been established.
authors.affiliation: Division of Metabolism and Biosystemic Science, Department of Internal Medicine, Asahikawa Medical College, Asahikawa, Hokkaido, Japan.
authors.forename: Yosui
authors.initials: Y
authors.lastname: Tamaki
authors.forename: Yukiomi
authors.initials: Y
authors.lastname: Nakade
authors.forename: Taeko
authors.initials: T
authors.lastname: Yamauchi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Makino
authors.forename: Shiro
authors.initials: S
authors.lastname: Yokohama
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Okada
authors.forename: Kazunobu
authors.initials: K
authors.lastname: Aso
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kanamori
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Ohashi
authors.forename: Ken
authors.initials: K
authors.lastname: Sato
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Nakao
authors.forename: Masakazu
authors.initials: M
authors.lastname: Haneda
authors.forename: Masashi
authors.initials: M
authors.lastname: Yoneda
mesh_terms: D000596:Amino Acids / Q000008:administration & dosage; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001565:Benzoates / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000517:prevention & control*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D002796:Choline Deficiency / Q000150:complications; D004032:Diet / Q000009:adverse effects; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005234:Fatty Liver / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis / Q000235:genetics; D008099:Liver / Q000098:blood supply; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000517:prevention & control; D065626:Non-alcoholic Fatty Liver Disease; D051381:Rats; D017208:Rats, Wistar; D000077333:Telmisartan; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000596:Amino Acids; D047228:Angiotensin II Type 1 Receptor Blockers; D016588:Anticarcinogenic Agents; D001562:Benzimidazoles; D001565:Benzoates; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D000077333:Telmisartan