Angiotensin II Type 1 Receptor Antagonist Improves
the Prognosis in Rats Displaying Liver Cirrhosis Induced by a Choline-Deficient
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Kaoru Iwata, Tetsuro Sohda, Makoto Irie, Yasuaki Takeyama,
Akira Anan, Satoshi Shakado, Shotaro Sakisaka
Department of Gastroenterology and Medicine, Fukuoka University
School of Medicine, Fukuoka, Japan
Background. Angiotensin II type 1 receptor (AT1)
antagonists are known to suppress TGFß and lipid peroxidation.
An experimental rat model made by feeding rats a choline-deficient
diet (CDD) showed severe steatosis, fibrosis and infiltration
of inflammatory cells in the liver resembling nonalcoholic steatohepatitis
(NASH). NASH causes fibrosis by lipid peroxidation. In this study,
we assess whether AT1 antagonists and angiotensin II type 2 receptor
(AT2) antagonists can suppress the hepatic fibrosis and lipid
peroxidation in CDD rats that lead to the development of NASH.
Methods: Both study groups received subcutaneously
aqueous solutions of AT2 antagonist (PD123319 - 1 mg/kg/day) and
AT1 antagonist (L158809 - 1 mg/kg/day), respectively, 6 times
per week. On day 90, some rats (5 /group) were sacrificed by excision
of the liver under anesthesia, in order to assess the hepatic
hydroxyproline (HP), malondialdehyde (MDA), total glutathione,
superoxide dismutase (SOD) activity and TGFß-1. The remaining
rats were maintained to observe the survival rate.
Results: All CDD rats developed liver cirrhosis.
However, the tissue TGF and HP decreased in AT1 antagonist group
in comparison with the other two groups. All groups of CDD rats
showed strong adipose hyperoxidation. The AT1 antagonist group
demonstrated a markedly improved survival rate in comparison to
the other two groups.
Conclusion: Hepatic fibrosis progression in
the AT1 antagonist group was slower than that in the other groups.
This observation suggests that AT1 antagonists delayed the progression
of liver failure, which thus led to an improved survival rate.
Angiotensin II receptor - choline-deficient diet - nonalcoholic
steatohepatitis - lipid peroxidation - hepatic