Abstract
BackgroundHepatic schistosomiasis is considered to be one of the most prevalent forms of chronic liver disease in the world due to its complication of liver fibrosis. The demonstration of the pro-fibrogenic role of angiotensin (Ang) II in chronic liver disease brought up the idea that anti-Ang II agents may be effective in improving hepatic fibrosis by either blocking Ang II type 1 (AT1) receptors or inhibiting the angiotensin converting enzyme. Peroxisome proliferator-activated receptors gamma (PPARγ) activation has been also shown to inhibit hepatic stellate cell activation and progression of fibrosis. The present study has aimed at testing the anti-fibrogenic effects of telmisartan; an AT1 receptor blocker and a PPARγ partial agonist, alone or combined with praziquantel (PZQ) on Schistosoma mansoni-induced liver fibrosis in mice.MethodsTo achieve the aim of the study, two sets of experiments were performed in which telmisartan was initiated at the 5th (set 1) and the 10th (set 2) weeks post infection to assess drug efficacy in both acute and chronic stages of liver fibrosis, respectively. Schistosoma mansoni-infected mice were randomly divided into the following four groups: infected-control (I), telmisartan-treated (II), PZQ-treated (III), and telmisartan+PZQ-treated (IV). In addition, a normal non-infected group was used for comparison. Parasitological (hepatomesenteric worm load and oogram pattern), histopathological, morphometric, immunohistochemical (hepatic expressions of matrix metalloproteinase-2; MMP-2 and tissue inhibitor of metalloproteinase-2; TIMP-2), and biochemical (serum transforming growth factor beta 1; TGF-β1 and liver function tests) studies were performed.ResultsTelmisartan failed to improve the parasitological parameters, while it significantly (P<0.05) decreased the mean granuloma diameter, area of fibrosis, and serum TGF-β1. Additionally, telmisartan increased MMP-2 and decreased TIMP-2 hepatic expression. Combined treatment failed to show any additive properties, yet it did not affect the anti-schistosomal activity of PZQ.ConclusionsThese results suggest potential anti-fibrotic effects of telmisartan, an AT1 receptor blocker and a PPARγ partial agonist, in acute and chronic stages of Schistosoma mansoni–induced liver fibrosis in mice.
Highlights
Hepatic schistosomiasis is considered to be one of the most prevalent forms of chronic liver disease in the world due to its complication of liver fibrosis
These results suggest potential anti-fibrotic effects of telmisartan, an Ang II type 1 (AT1) receptor blocker and a PPARγ partial agonist, in acute and chronic stages of Schistosoma mansoni–induced liver fibrosis in mice
Infection An Egyptian strain of Schistosoma mansoni cercariae was provided by the Schistosome Biology Supply Center (SBSC) of Theodor Bilharz Research Institute (TBRI)
Summary
Hepatic schistosomiasis is considered to be one of the most prevalent forms of chronic liver disease in the world due to its complication of liver fibrosis. The present study has aimed at testing the anti-fibrogenic effects of telmisartan; an AT1 receptor blocker and a PPARγ partial agonist, alone or combined with praziquantel (PZQ) on Schistosoma mansoni-induced liver fibrosis in mice. The World Health Organization (WHO) has defined seventeen of these conditions as core NTDs [1] One of these NTDs is schistosomiasis which is a major parasitic disease, caused by blood flukes (trematode worms) of the genus Schistosoma (S.), affecting millions of people worldwide. It is endemic in about 76 countries and territories, though it is estimated that 85% of the infected people are on the African continent [2]. There are recent concerns about tolerance or resistance to PZQ, and monitoring its efficacy in different settings is required [3]
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