Telmisartan, an angiotensin II type 1 receptor blocker, controls progress of nonalcoholic steatohepatitis in rats.
The term nonalcoholic steatohepatitis (NASH) has recently been proposed to identify a fatty liver disease accompanied by diffuse fatty infiltration and inflammation. However, no drug therapy has been established for NASH as yet. In the present study, we demonstrate the effect of the angiotensin II type 1 receptor antagonist telmisartan on the development of NASH in a rat model. Telmisartan, but not the angiotensin receptor antagonist valsartan, markedly attenuated hepatic steatosis, inflammation, and fibrosis in these rats. The quantitative parameters of steatosis, inflammation, and fibrosis were also ameliorated by treatment with telmisartan. Compared with telmisartan, the peroxisome proliferator-activated receptor-gamma agonist pioglitazone attenuated hepatic steatosis and fibrosis of the liver to a similar degree. However, telmisartan, but not pioglitazone, dramatically decreased both subcutaneous and visceral fat. In conclusion, these results indicated that telmisartan should be the drug of first choice for the treatment of patients with NASH.
Fujita
Koji
K
Division of Gastroenterology, Yokohama City University Graduate School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, Japan.
Yoneda
Masato
M
Wada
Koichiro
K
Mawatari
Hironori
H
Takahashi
Hirokazu
H
Kirikoshi
Hiroyuki
H
Inamori
Masahiko
M
Nozaki
Yuichi
Y
Maeyama
Shiro
S
Saito
Satoru
S
Iwasaki
Tomoyuki
T
Terauchi
Yasuo
Y
Nakajima
Atsushi
A
D000199:Actins / Q000096:biosynthesis; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001562:Benzimidazoles / Q000627:therapeutic use*; D001565:Benzoates / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D024042:Collagen Type I / Q000096:biosynthesis; D004195:Disease Models, Animal; D018450:Disease Progression; D005234:Fatty Liver / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007150:Immunohistochemistry; D008297:Male; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism; D000077205:Pioglitazone; D051381:Rats; D011916:Rats, Inbred F344; D013053:Spectrophotometry; D000077333:Telmisartan; D013777:Tetrazoles / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000627:therapeutic use; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000068756:Valsartan
D000199:Actins; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D015415:Biomarkers; D024042:Collagen Type I; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D013777:Tetrazoles; D045162:Thiazolidinediones; D000068756:Valsartan; D014633:Valine; D000077333:Telmisartan; D000077205:Pioglitazone