Losartan, an angiotensin-II type 1 receptor blocker, attenuates the liver fibrosis development of non-alcoholic steatohepatitis in the rat.
BACKGROUND
Apart from simple steatosis, the non-alcoholic steatohepatitis (NASH) can progress into liver fibrosis and cirrhosis. To date, however, no widely accepted therapeutic modalities have been established against NASH in the clinical practice. To find out promising new therapeutic agents, it is important to employ an appropriate experimental model of NASH, such as association with insulin resistance.


RESULTS
In the current study, we found that losartan, a clinically used angiotensin-II type 1 receptor blocker, significantly attenuated a choline-deficient L-amino acid-defined (CDAA) diet-induced steatohepatitis in obese diabetic- and insulin resistance-associated Otsuka Long-Evans Tokushima Fatty (OLETF) rats. The transforming growth factor-beta, a well-known major fibrogenic cytokine, was also suppressed in a similar magnitude to that of the fibrosis area. Noteworthy was the finding that these inhibitory effects were achieved even at a clinically comparable low dose.


CONCLUSIONS
Since losartan is widely used without serious side effects in the clinical practice, this agent may be an effective new therapeutic strategy against NASH.
Third Department of Internal Medicine, Nara Medical University, Shijo-cho 840, Kashihara, Nara 634-8522, Japan. yoshijih@naramed-u.ac.jp
Hitoshi
H
Yoshiji
Ryuichi
R
Noguchi
Yasuhide
Y
Ikenaka
Tadashi
T
Namisaki
Mitsuteru
M
Kitade
Kosuke
K
Kaji
Yusaku
Y
Shirai
Junichi
J
Yoshii
Koji
K
Yanase
Masaharu
M
Yamazaki
Tatsuhiro
T
Tsujimoto
Hideto
H
Kawaratani
Takemi
T
Akahane
Yosuke
Y
Aihara
Hiroshi
H
Fukui