Telmisartan, an AT1 receptor blocker and a PPAR gamma activator, alleviates liver fibrosis induced experimentally by Schistosoma mansoni infection.
Telmisartan, an AT1 receptor blocker and a PPAR gamma activator, alleviates liver fibrosis induced experimentally by Schistosoma mansoni infection.
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DOI：
10.1186/1756-3305-6-199
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发表时间：
2013-07-05
影响因子：
3.2
通讯作者：
El-Khatib AS
中科院分区：
文献类型：
--
作者：
Attia YM;Elalkamy EF;Hammam OA;Mahmoud SS;El-Khatib AS
肝血吸虫病因其并发肝纤维化而被认为是世界上最常见的慢性肝病之一。血管紧张素（Ang）II在慢性肝病中的促纤维化作用的证明提出了抗Ang II药物可能通过阻断Ang II 1型（AT 1）受体或抑制血管紧张素转化酶而有效改善肝纤维化的想法。过氧化物酶体增殖物激活受体γ（过氧化物酶体增殖物激活受体γ）的激活也被证明可以抑制肝星状细胞的激活和纤维化的进展。本研究旨在检测替米沙坦（一种AT 1受体阻断剂和一种PPARγ部分激动剂）单独或与吡喹酮（PZQ）联合使用对曼氏血吸虫诱导的小鼠肝纤维化的抗纤维化作用。为了实现研究目的，进行了两组实验，分别在感染后第5周（第1组）和第10周（第2组）开始替米沙坦给药，以评估药物在肝纤维化急性和慢性阶段的疗效。将曼氏血吸虫感染小鼠随机分为以下四组：感染对照组（I）、替米沙坦治疗组（II）、PZQ治疗组（III）和替米沙坦+PZQ治疗组（IV）。此外，正常非感染组用于比较。进行了寄生虫学（肝肠系膜蠕虫负荷和卵图模式）、组织病理学、形态计量学、免疫组织化学（基质金属蛋白酶-2; MMP-2和金属蛋白酶组织抑制剂-2; TIMP-2的肝脏表达）和生化（血清转化生长因子β 1; TGF-β1和肝功能检查）研究。替米沙坦未能改善寄生虫学参数，但显著（P<0.05）降低了平均肉芽肿直径、纤维化面积和血清TGF-β1。此外，替米沙坦增加MMP-2和降低TIMP-2肝脏表达。联合处理未能显示出任何累加特性，但它不影响PZQ的抗染色体活性。这些结果表明，替米沙坦（一种AT 1受体阻滞剂和一种PPARγ部分激动剂）在曼氏血吸虫诱导的小鼠肝纤维化急性和慢性阶段具有潜在的抗纤维化作用。
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 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. To 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. Telmisartan 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. These 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.
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影响因子：
2.7
作者：
Engels D;Chitsulo L;Montresor A;Savioli L
通讯作者：
Savioli L
DOI：
10.1007/bf00389899
发表时间：
1977-01-01
期刊：
ZEITSCHRIFT FUR PARASITENKUNDE-PARASITOLOGY RESEARCH
影响因子：
--
作者：
GONNERT, R;ANDREWS, P
通讯作者：
ANDREWS, P
影响因子：
6.1
作者：
Cheng Yang;Ping Jian;Xu Lie-ming
通讯作者：
Xu Lie-ming
影响因子：
29.4
作者：
Bataller, R;Ginès, P;Rodés, J
通讯作者：
Rodés, J
DOI：
10.1590/s0074-02762003000700011
发表时间：
2003-10-01
期刊：
Memórias do Instituto Oswaldo Cruz
影响因子：
--
作者：
Coutinho, Eridan M;Barros, Andréia F;Andrade, Zilton A
通讯作者：
Andrade, Zilton A