Potential Anti-Fibrotic Effect of Direct Acting Antiviral Drugs on CCl4 Induced Hepatic Fibrosis in Rats

A. El-sisi, Sherin Zakaria
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引用次数: 4

Abstract

Background: Hepatic fibrosis is a hall mark of chronic liver diseases such as chronic HCV. Direct acting antiviral (DAA) regimens such as Sofosbuvir (SOF) and daclatasvir (DAC) have been found to be associated with decreased fibrotic markers in HCV patients. It is not clear however the reported antifibrotic effect is antiviral dependent or not. Aim: This study investigated the effect of SOF and DAC in hepatic fibrosis induced by CCl4 in rats. Method: Hepatic fibrosis was induced by (0.5 ml/kg) CCl4 IP twice a week for six weeks. SOF (20 mg/kg/d) and DAC (30 mg/kg/d) were added in the last four weeks of treatments. Liver functions, fibrotic markers such as Hyaluronic acid and metalloproteinase-9 were detected using immunoassay. Liver tissues were examined by different stains. Results: SOF and DAC induced marked inhibitions in fibrotic markers expression significantly (P≤0.001). Moreover, the drugs protected liver tissues from progressed fibrosis. Conclusion: SOF/DAC antifibrotic effect is independent on its antiviral activity.
直接作用抗病毒药物对CCl4诱导大鼠肝纤维化的潜在抗纤维化作用
背景:肝纤维化是慢性肝病(如慢性丙型肝炎)的标志。直接作用抗病毒(DAA)方案,如索非布韦(SOF)和daclatasvir (DAC)已被发现与HCV患者纤维化标志物降低相关。然而,目前尚不清楚报道的抗纤维化作用是否依赖于抗病毒药物。目的:探讨sofd和DAC在CCl4致大鼠肝纤维化中的作用。方法:用(0.5 ml/kg) ccl4ip诱导肝纤维化,每周2次,连续6周。在最后4周添加sof20 mg/kg/d和DAC 30 mg/kg/d。采用免疫分析法检测肝功能、透明质酸、金属蛋白酶-9等纤维化标志物。用不同的染色方法检查肝组织。结果:SOF和DAC均能显著抑制纤维化标志物的表达(P≤0.001)。此外,这些药物还能防止肝组织发生进展性纤维化。结论:SOF/DAC抗纤维化作用与抗病毒活性无关。
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