Telmisartan prevents hepatic fibrosis and enzyme-altered lesions in liver cirrhosis rat induced by a choline-deficient L-amino acid-defined diet.
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.
Jin
Haiyan
H
Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Minami-Kogushi 1-1-1 Ube, Yamaguchi 755-8505, Japan.
Yamamoto
Naoki
N
Uchida
Koichi
K
Terai
Shuji
S
Sakaida
Isao
I
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage; D000818:Animals; D001562:Benzimidazoles / Q000008:administration & dosage*; D001565:Benzoates / Q000008:administration & dosage*; D002796:Choline Deficiency / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D050830:L-Amino Acid Oxidase / Q000172:deficiency*; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D000077333:Telmisartan; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001565:Benzoates; D050830:L-Amino Acid Oxidase; D000077333:Telmisartan