Aim: 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 (CCl4)‐induced liver fibrosis was examined.
Methods: Liver fibrosis was induced by the s.c. injection of 1 mL/kg of CCl4 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.
Results: 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 placebo‐treated group. A significant decrease in the number of α‐smooth muscle actin (SMA)‐positive cells was seen in the TY‐51469‐treated group compared to the placebo‐treated group.
Conclusion: Significant correlations between the number of chymase‐positive cells and the degree of fibrosis and between the numbers of chymase‐positive cells and α‐SMA‐positive cells were observed. Thus, chymase inhibition may be a useful strategy for preventing liver fibrosis.