Prevention and regression of non-alcoholic steatohepatitis (NASH) in a rat model by metabosartan, telmisartan.
The favorable metabolic effects of telmisartan have been attributed to its angiotensin II receptor blockade and action as a partial agonist of peroxisome proliferator-activated receptor (PPAR)-gamma. We previously reported that administration of telmisartan markedly inhibited lipid accumulation in the liver in mice fed a high-fat diet. In the present study, we further examined the protective effect of telmisartan in a non-alcoholic steatohepatitis (NASH) model induced by feeding Wistar rats an L-methionine- and choline-deficient (MCA) diet. In the first experiment, rats were fed an MCA diet for 8 weeks with or without telmisartan (3 mg/kg/day). Liver fibrosis was observed by Masson trichrome staining, and co-treatment was shown to attenuate liver fibrosis. In the second experiment, Wistar rats were fed an MCA diet for 20 weeks, and telmisartan (3 mg/kg/day) was administered during weeks 0-20 as a preventive model or weeks 8-20 as a therapeutic model. As a result, telmisartan administration in both models significantly attenuated liver fibrosis and an increase in serum AST. Of importance, the HGF concentration in the liver was significantly increased in the telmisartan-treated group. Overall, telmisartan showed a potential action to improve NASH induced by an MCA diet, possibly due to increased HGF production through partial agonist of PPAR-gamma. These favorable characteristics of telmisartan as a partial agonist of PPAR-gamma may provide a benefit in the treatment of metabolic syndrome beyond its blood pressure-lowering effect.
Nakagami
Hironori
H
Department of Gene Therapy Science, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Kiomy Osako
Mariana
M
Nakagami
Futoshi
F
Shimosato
Takashi
T
Minobe
Noriko
N
Moritani
Toshinori
T
Shimamura
Munehisa
M
Miyake
Takashi
T
Shimizu
Hideo
H
Takeya
Yasushi
Y
Morishita
Ryuichi
R
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D001562:Benzimidazoles / Q000627:therapeutic use*; D001565:Benzoates / Q000627:therapeutic use*; D005234:Fatty Liver / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control*; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000473:pathology; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000077333:Telmisartan
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D047495:PPAR gamma; D017228:Hepatocyte Growth Factor; D000077333:Telmisartan