Department of Parasitology, Basic Medical College, Dalian Medical University, Dalian 116044, Liaoning, China.
Wuhan Fourth Hospital: Puai Hospital, Tongi Medical College, Huazhong University of Science and Technology, Wuhan 430000, Hubei, China.
Int Immunopharmacol. 2020 Aug;85:106512. doi: 10.1016/j.intimp.2020.106512. Epub 2020 May 23.
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.
华支睾吸虫作为食源性寄生虫，可在肝内胆管引起炎症、上皮增生和纤维化，与胆管癌（CCA）的发生有关。吡喹酮是治疗这种寄生虫最有效的药物。然而，由于吡喹酮的副作用及其与 CCA 的风险，急需开发对宿主毒性最小的新药。在这项研究中，蠕虫线粒体呼吸链抑制剂 Wortmannilatone F（WF）和 IL-8 类似物 CXCL8（3-72）K11R/G31P 被用于治疗感染华支睾吸虫的 BALB/C 小鼠。我们研究了肝的大体和组织病理学形态、炎症相关细胞因子 IL-6、脂质过氧化相关蛋白环氧化酶-2（COX-2）和 5-脂氧合酶（5-LOX）、胶原纤维积累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），以及体外对这些寄生虫的消毒效果。WF 显著抑制和杀死了蠕虫，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 的组合是治疗华支睾吸虫感染的一种潜在治疗方法。
