Institute of Pathogenic Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
Vet Res. 2019 Nov 19;50(1):96. doi: 10.1186/s13567-019-0710-7.
While searching for novel anti-echinococcosis drugs, we have been focusing on glycolysis which is relied on by Echinococcus for energy production and intermediates for other metabolic processes. The aim of this study was to investigate the potential therapeutic implication of glycolytic inhibitors on Echinococcus. Our results demonstrate that at an initial concentration of 40 μM, all inhibitors of glycolysis used in the current experiment [3-bromopyruvate (3-BrPA), ornidazole, clorsulon (CLS), sodium oxamate and 2,6-dihydroxynaphthalene (NA-P)] show considerable in vitro effects against Echinococcus granulosus protoscoleces and Echinococcus multilocularis metacestodes. Among them, 3-BrPA exhibited the highest activity which was similar to that of nitazoxanide (NTZ) and more efficacious than albendazole (ABZ). The activity of 3-BrPA was dose dependent and resulted in severe ultrastructural destructions, as visualized by electron microscopy. An additional in vivo study in mice infected with E. multilocularis metacestodes indicates a reduction in parasite weight after the twice-weekly treatment of 25 mg/kg 3-BrPA for 6 weeks, compared to that of the untreated control. In particular, in contrast to ABZ, the administration of 25 mg/kg 3-BrPA did not cause toxicity to the liver and kidney in mice. Similarly, at the effective dose against Echinococcus larvae, 3-BrPA showed no significant toxicity to human hepatocytes. Taken together, the results suggest that interfering with the glycolysis of the parasite may be a novel chemotherapeutical option and 3-BrPA, which exhibited a remarkable activity against Echinococcus, may be a promising potential drug against cystic echinococcosis (CE) and alveolar echinococcosis (AE).
在寻找新型抗包虫病药物时，我们一直专注于糖酵解，这是包虫用于产生能量和其他代谢过程中间产物的途径。本研究旨在探讨糖酵解抑制剂对包虫的潜在治疗意义。我们的研究结果表明，在所使用的糖酵解抑制剂中[3-溴丙酮酸（3-BrPA）、奥硝唑、氯硝柳胺（CLS）、草酸钠和 2,6-二羟基萘（NA-P）]，在初始浓度为 40 μM 时，所有抑制剂对细粒棘球蚴原头蚴和泡球蚴原头节均具有明显的体外作用。其中，3-BrPA 的活性最高，与硝唑尼特（NTZ）相似，且比阿苯达唑（ABZ）更有效。3-BrPA 的活性呈剂量依赖性，导致超微结构严重破坏，电镜下可见。在感染泡球蚴原头节的小鼠体内的进一步研究表明，与未治疗的对照组相比，每周两次以 25 mg/kg 3-BrPA 治疗 6 周后，寄生虫的重量明显减轻。特别是与 ABZ 不同，25 mg/kg 3-BrPA 的给药不会导致小鼠的肝和肾毒性。同样，在对细粒棘球蚴幼虫有效的剂量下，3-BrPA 对人肝细胞没有明显毒性。综上所述，这些结果表明，干扰寄生虫的糖酵解途径可能是一种新的化学治疗选择，具有显著抗包虫活性的 3-BrPA 可能是一种有前途的治疗囊性包虫病（CE）和泡型包虫病（AE）的潜在药物。
