Chymase inhibition attenuates tetrachloride-induced liver fibrosis in hamsters

Hepatology Research : the Official Journal of the Japan Society of Hepatology
Koji KomedaMizuo Miyazaki

Abstract

Chymase converts angiotensin I to angiotensin II, which may promote the development of liver fibrosis. In this study, whether a chymase inhibitor TY-51469 attenuated tetrachloride (CCl(4))-induced liver fibrosis was examined. Liver fibrosis was induced by the s.c. injection of 1 mL/kg of CCl(4) twice weekly for 8 weeks, and each hamster was given TY-51469 (1 mg/kg per day) or placebo. Untreated hamsters were used as a control group. Significant increases of serum alanine aminotransferase, total bilirubin and hyaluronic acid levels were observed in the placebo-treated group compared with the control group, but these levels were significantly attenuated in the TY-51469-treated group. Liver chymase activity was significantly higher in the placebo-treated group than in the control group, whereas the activity in the TY51469-treated group was not. Total angiotensin II-forming activity in the liver was also significantly higher in the placebo-treatedgroup than in the control group or the TY-51469-treated group. The ratio of the fibrotic area to the total area in the liver was significantly higher in the placebo-treated group than in the control group, but the ratio was significantly lower in the TY-51469-treated group than in the plac...Continue Reading

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Citations

Jan 11, 2013·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Shinsuke MasubuchiKazuhisa Uchiyama
Feb 5, 2011·Expert Opinion on Therapeutic Targets·Shinji TakaiMizuo Miyazaki
Feb 16, 2012·Journal of Pharmacological Sciences·Shinji TakaiMizuo Miyazaki
Jan 20, 2018·Circulation Research·Louis J Dell'ItaliaCarlos M Ferrario
Oct 4, 2019·Liver International : Official Journal of the International Association for the Study of the Liver·Giovanni SansoèFlorence Wong
Mar 9, 2018·Frontiers in Pharmacology·Shinji Takai, Denan Jin
Feb 13, 2018·Immunological Reviews·Peter Bradding, Gunnar Pejler
Nov 27, 2019·Cells·Ralf WeiskirchenMichael Huber

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