Comparison of Different Blockages on the Renin Angiotensin System in Murine Schistosomal Fibrosis

Abstract

 The inhibition of the renin-angiotensin system (RAS) display anti-fibrogenic effects in liver cirrhosis, however RAS influence on schistosomal fibrosis has not been totally clarified. Thus, our objective was to compare the activities of different antihypertensive drugs on the inhibition of the RAS in murine schistosomal fibrosis. BALB/c mice (n=40) weighing 20g were subjected to inoculation of 50 cercariae and subdivided in three groups: the first group (n=15), animals were treated with losartan (10 mgkg-1 body weight); the second group (n=15) was treated with lisinopril (10 mgkg-1 body weight); while the third group (n=10) was treated with proportional volume of 0.9% NaCl, daily for 12 weeks. For this purpose, histological analysis, RT-PCR of genes related to hepatic fibrosis, as well as TGFβ1 and p42/44 MAPK protein quantification were evaluated. There was observed a decrease in the collagen deposits in animals treated with losartan (p<0.01) and lisinopril (p<0.01) once compared to the controls. This improvement was accompanied by a reduction of α-SMA labeled cells (p<0.001 and p<0.001) and procollagen α1(I) gene expression in both treated groups (p<0.05 and p<0.05). However, only losartan induced diminution of TGFβ1 and TIMP1 gene expression (p<0.01 and p<0.01), and TGFβ1 protein amount. Diversely, p42/44 MAPK protein was augmented in lisinopril group. Our findings demonstrated the effect of lisinopril and losartan on the decrease of hepatic fibrosis in murine schistosomiasis. The main mechanism of this process involves anti-fibrogenic activity via inhibition of TGFβ1 and TIMP1 by losartan treatment. Nevertheless, other possible mechanisms associated to lisinopril treatment may be implicated