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Impact of Wortmannilactone F and G31P on Clonorchis Sinensis-infected mice.
International Immunopharmacology ( IF 5.6 ) Pub Date : 2020-05-23 , DOI: 10.1016/j.intimp.2020.106512
Yuanhua Qin 1 , Zhongpei Zhang 2 , Lili Zheng 1 , Haiyan Wu 3 , Xiaodong Dai 1 , Yuesheng Dong 4 , Yu Cui 1 , Yixin Ren 1
Affiliation  

Clonorchis sinensis could induce inflammation, epithelial hyperplasia and fibrosis in the intrahepatic bile duct as a food-borne parasite, which was associated with the development of cholangiocarcinoma (CCA). Praziquantel was the most effective drug on treatment of this kind of parasite. However, new drugs with minimal toxicity to the host were urgently needed due to the side effects of Praziquantel and its CCA risk. In this study, helminth mitochondria respiratory chain blocker Wortmannilatone F (WF) and IL-8 analogue CXCL8 (3–72) K11R/G31P were used to treat BALB/C mice infected by Clonorchis sinensis. We investigated the gross and histopathological morphology of the liver, inflammation-associated cytokine IL-6, lipid peroxidation-related proteins cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), collagen fiber accumulation and fibroblast-specific protein 1 (FSP1), malignant markers proliferating cell nuclear antigen (PCNA) and cytokeratin 19 (CK19), as well as the disinfection effect on these parasites in vitro. WF inhibited and killed the worms dramatically, and the combination of WF with G31P improved the condition of the hepatobiliary duct tissue greatly. These outcomes indicated that the combination of WF and G31P was a potential therapeutic method to treat the Clonorchis sinensis infection.



中文翻译:

Wortmannilactone F和G31P对中华支睾吸虫感染小鼠的影响。

华支睾吸虫可通过食源性寄生虫在肝内胆管中引起炎症,上皮增生和纤维化,这与胆管癌的发展有关。吡喹酮是治疗这种寄生虫的最有效药物。然而,由于吡喹酮的副作用及其CCA风险,迫切需要对宿主毒性最小的新药。在这项研究中,蠕虫线粒体呼吸链阻滞剂Wortmannilatone F(WF)和IL-8类似物CXCL8(3-72)K11R / G31P被用于治疗被华支睾吸虫感染的BALB / C小鼠。我们研究了肝脏的总体和组织病理学形态,炎症相关的细胞因子IL-6,脂质过氧化相关的蛋白cyclooxygenase-2(COX-2)和5-lipoxygenase(5-LOX),胶原纤维积聚和成纤维细胞特异性蛋白1(FSP1),恶性标志物增殖细胞核抗原(PCNA)和细胞角蛋白19(CK19),以及在体外对这些寄生虫的消毒作用。WF显着抑制并杀死了该蠕虫,并且WF与G31P的组合极大地改善了肝胆管组织的状况。这些结果表明,WF和G31P的结合是治疗中华支睾吸虫感染的一种潜在的治疗方法

更新日期:2020-05-23
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