The comparative efficacy of renin-angiotensin system blockers in schistosomal hepatic fibrosis

Author(s)

Parreira, Natallia Alle ^[1] ; Ramalho, Fernando Silva ^[1] ; Augusto, Marlei Josiele ^[1] ; Silva, Deisy Mara ^[1] ; Prado, Cibele Maria ^[1] ; Elias Junior, Jorge ^[2] ; Rodrigues, Vanderlei ^[3] ; Zambelli Ramalho, Leandra Naira ^[1]

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pathol, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Med, Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Cell & Mol Biol & Pathogen Bioagents, Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Experimental Parasitology; v. 191, p. 9-18, AUG 2018.
• Web of Science Citations: 0

Abstract

Schistosomiasis mansoni is involved in hepatic fibrogenesis and portal hypertension. Previous studies proved that blockade of some components of the renin-angiotensin system (RAS) reduce liver fibrogenesis. However, the effects of inhibition of early stages of RAS pathway in schistosomal fibrosis have not been studied yet. Thus, the aim of this study was to compare the role of different antihypertensive drugs on hepatic fibrosis in murine schistosomiasis. BALB/c mice (n = 50) weighing 20g were subjected to inoculation of 50 cercariae and submitted to different treatments: aliskiren, 50 mg/kg (n = 10); bradykinin, 2 mu g/kg (n = 5); losartan, 10 mg/kg (n = 10); lisinopril 10 mg/kg (n = 5) and control, proportional volume vehicle (n = 5); daily for 14 weeks. Six animals were not subjected to cercariae inoculation or any type of treatment. Ultrasound, histological, immunohistochemical and proteomic analyzes were performed to evaluate markers associated with hepatic fibrogenesis. The hepatic areas stained with Sirius red and thenumber of cells marked by alpha-SMA in animals treated with aliskiren, bradykinin, lisinopril and losartan were diminished when compared to control group, demonstrating reduced hepatic fibrosis after RAS blockade. These results were reinforced by ultrasonography analysis and protein expression of TGF beta. These findings demonstrated the effect of RAS inhibition on hepatic fibrosis in murine schistosomiasis, with the most evident results being observed in the losartan and aliskiren treated groups. The main mechanisms underlying this process appear to involve anti-fibrogenic activity through the inhibition of collagen and TGF beta synthesis. (AU)

• FAPESP's process: 08/01296-2 - Effect of caffeic acid phenethyl ester on hepatic ischemia and reperfusion injury after experimental liver transplantation
• Grantee: Sérgio Zucoloto
• Support Opportunities: Regular Research Grants