Telmisartan prevents hepatic fibrosis and enzyme-altered lesions in liver cirrhosis rat induced by a choline-deficient L-amino acid-defined diet

Biochem Biophys Res Commun. 2007 Dec 28;364(4):801-7. doi: 10.1016/j.bbrc.2007.10.083. Epub 2007 Oct 24.

Abstract

Rennin-angiotensin system is involved in liver fibrogenesis through activating hepatic stellate cells (HSCs). Telmisartan (Tel) is an angiotensin II type 1 receptor antagonist, could function as a selective peroxisome proliferator-activated receptor gamma activator. Here we studied the effect of Tel on liver fibrosis, pre-neoplastic lesions in vivo and primary HSCs in vitro. In vivo study, we used the choline-deficient L-amino acid-defined (CDAA)-diet induced rat NASH model. The rats were fed the CDAA diet for 8 weeks to induce liver fibrosis and pre-neoplastic lesions, and then co-administrated with Tel for another 10 weeks. Tel prevented liver fibrogenesis and pre-neoplastic lesions by down-regulating TGFbeta1 and TIMP-1, 2 and increasing MMP-13 expression. Tel inhibited HSCs activation and proliferation. These results suggested that Tel could be a promising drug for NASH related liver fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Animals
  • Benzimidazoles / administration & dosage*
  • Benzoates / administration & dosage*
  • Choline Deficiency / complications
  • Choline Deficiency / diagnosis
  • Choline Deficiency / drug therapy*
  • Dose-Response Relationship, Drug
  • L-Amino Acid Oxidase / deficiency*
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / etiology
  • Liver Cirrhosis / prevention & control*
  • Male
  • Rats
  • Rats, Wistar
  • Telmisartan
  • Treatment Outcome

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Benzimidazoles
  • Benzoates
  • L-Amino Acid Oxidase
  • Telmisartan