Cystic echinococcosis (CE), caused by the cestode Echinococcus granulosus, is a worldwide chronic zoonosis. Albendazole (ABZ) and mebendazole are effective against CE, but a high dosage in a long-term period is usually required. In this study, we evaluate the effects of DNA damage repair inhibitor (i.e., Veliparib) in combination with artesunate (AS) on hydatid cysts. For the in vitro assay, protoscoleces of E. granulosus (E.g PSCs) were incubated with low AS (AS-L, 65 μM), moderate AS (AS-M, 130 μM), and high AS (AS-H, 325 μM), AS-L/M/H+Veliparib (10 μM), and ABZ (25 μM), respectively. The AS-H+Veliparib group showed the maximal protoscolicidal effects. Ultrastructural change revealed that germinal layer (GL) cells were reduced, and lipid droplets appeared. AS could induce DNA injuries in PSCs. The 8-OHdG was expressed in the PSCs and GL of the cysts in mice, especially in the presence of Veliparib. The most severe DNA damages were observed in the AS-H+Veliparib group. Meanwhile, the expression of ribosomal protein S9 (RPS9) gene in the AS-H+Veliparib group was significantly lower than that in the AS-H group. The in vivo chemotherapeutic effects of AS-L (50 mg/kg), AS-H (200 mg/kg), and AS-H+Veliparib (25 mg/kg) were assessed in experimentally infected mice. Upon 6 weeks of oral administration, ultrasonography was used to monitor the volume change of vesicles. Maximum potentiation was seen on day 15 with values (versus AS) of 34 () for AS-H + Veliparib. It led to the reduction of cyst weight (55.40%) compared with the model group (), which was better than AS alone (52.84%) and ABZ-treated mice (55.35%). Analysis of cysts collected from AS-H+Veliparib-treated mice by transmission electron microscopy revealed a drug-induced structural destruction. The structural integrity of the germinal layer was lost, and the majority of the microtriches disappeared. In conclusion, our study demonstrates that AS or AS in combination with Veliparib is effective for treating CE, especially the combination group. On this basis, AS represented promising drug candidates in anti-CE chemotherapy.

中文翻译：

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DNA损伤修复抑制剂Veliparib联合青蒿琥酯对细粒棘球E虫的体外和体内功效。

囊尾棘球E虫（Echinococcus granulosus）引起的囊性棘球co病（CE）是一种世界范围的慢性人畜共患病。阿苯达唑（ABZ）和甲苯达唑对CE有效，但通常需要长期服用高剂量。在这项研究中，我们评估了DNA损伤修复抑制剂（即Veliparib）与青蒿琥酯（AS）联合治疗对包虫囊肿的影响。对于体外试验，的原头节细粒棘球绦虫（例如省电类别）与低AS（AS-L，65温育 μ M），中度AS（AS-M，130  μ M），和高的AS（AS-H， 325  μ M），AS-L / M / H + Veliparib（10  μ M），和ABZ（25  μM）。AS-H + Veliparib组表现出最大的促胃溃疡作用。超微结构变化表明生发层（GL）细胞减少，并出现脂质滴。AS可能在PSC中引起DNA损伤。8-OHdG在小鼠囊肿的PSC和GL中表达，尤其是在存在Veliparib的情况下。在AS-H + Veliparib组中观察到最严重的DNA损伤。同时，AS-H + Veliparib组的核糖体蛋白S9（RPS9）基因的表达明显低于AS-H组。在体内在实验感染的小鼠中评估了AS-L（50 mg / kg），AS-H（200 mg / kg）和AS-H + Veliparib（25 mg / kg）的化学治疗作用。口服6周后，使用超声检查来监测囊泡的体积变化。在第15天观察到最大增强，其值（相对于AS）为34（），用于AS-H + Veliparib。与模型组相比，囊肿重量减少了（55.40％）（），优于单独使用AS（52.84％）和ABZ治疗的小鼠（55.35％）。通过透射电子显微镜对从AS-H + Veliparib治疗的小鼠收集的囊肿进行分析，发现药物诱导的结构破坏。生发层的结构完整性消失了，大部分微干消失了。总之，我们的研究表明，AS或AS联合Veliparib可以有效治疗CE，尤其是联合治疗组。在此基础上，AS代表了抗CE化疗中有希望的候选药物。