Losartan, an angiotensin-II type 1 receptor blocker, attenuates CCl4-induced liver fibrosis with a positive impact on survival in mice

Abstract

Background: Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin-II receptor blockers (ARBs) may provide synergistic effects to existing chemotherapies by reducing angiotensin II-mediated angiogenesis, fibrogenesis, mitogenesis and oxidative stress.

Objective: We aimed to examine the effect of the ARB, losartan and the ACEIs, perindopril and fosinopril on carbon tetrachloride (CCl4)-induced liver fibrosis on the histopathologic level and assess their impact on survival of mice.

Methods: liver fibrosis was induced by CCl4 and examined histologically. Mice were treated with silymarin (SI) (30 mg/kg), perindopril (PE) (1 mg/kg), fosinopril (FO) (2 mg/ kg) or losartan (LO) (10 mg/kg). Cumulative survival was done using the Kaplan-Meier method and the log-rank test.

Results: The administration of PE and FO resulted in improved liver histology without survival benefits to mice. However, losartan demonstrated marked improvement of liver histology and a positive impact on survival which was comparable to silymarin.

Conclusion: Interfering the renin-angiotensin system (RAS) through the blockade of angiotensin-II type 1 (AT1) receptors improved liver histology of CCl4-induced hepatic fibrosis that was associated with longer survival in mice.