Volume 52, Number 12, 3455-3464, DOI: 10.1007/s10620-007-9741-4

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Gastroenterology Research Group

Telmisartan, An Angiotensin II Type 1 Receptor Blocker, Controls Progress of Nonalcoholic Steatohepatitis in Rats

Koji Fujita, Masato Yoneda, Koichiro Wada, Hironori Mawatari, Hirokazu Takahashi, Hiroyuki Kirikoshi, Masahiko Inamori, Yuichi Nozaki, Shiro Maeyama and Satoru Saito, et al.

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Abstract

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-γ 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.

Keywords  Steatosis - Fibrosis - Inflammation - AT-II blockade - PPAR-γ activation

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