Theodor Bilharz Research Institute, Giza, Egypt.
APMIS. 2010 Sep 1;118(9):692-702. doi: 10.1111/j.1600-0463.2010.02645.x.
Based on the fact that artemether (ART) affects immature schistosomes and that the effect of praziquantel (PZQ) mainly targets mature schistosomes, this work investigates the possible enhanced efficacy of PZQ in combination with ART in mice harboring a PZQ non-susceptible Schistosoma mansoni isolate. Associated schistosomal, inflammatory, hepatic histopathological changes have been investigated by examining the tissue markers expressing apoptosis using FAS (CD95), anti-apoptosis (Bcl2) and angiogenesis [vascular endothelial growth factor (VEGF)]. A batch of Swiss albino mice infected with a PZQ non-susceptible (EE10) S. mansoni isolate was divided into 12 groups. Animals of the first group were left without treatment as infected controls, while groups 2-6 received PZQ in increasing doses. The animals of group 7 received ART in double doses. Those comprising groups 8-12 received combined therapy of PZQ and ART in the same doses and at the same timings postinfection (PI) as those belonging to groups 2-6. Parasitological parameters, liver function, and histopathological and immunohistochemical studies of FAS, Bcl2 and VEGF antibodies were assessed. Combined administration of ART and PZQ reduced the ED(50) (the dose at which the worm burden was decreased by 50%) of PZQ. Typical granulomas were not seen in animals treated with ART alone and combined with PZQ, with least expression of FAS and VEGF and increased expression of Bcl2. The minimal histopathological changes recorded in mice treated with both ART and PZQ could be related to a synergistic/additive effect of ART, markedly reducing the intensity of infection. Improved liver function tests support the less severe histopathological changes under the influence of this treatment protocol. This study encourages human trials especially in areas where malaria is not endemic, and differing combination doses should be investigated in view of the antagonistic effect noticed with some dose regimens.
基于青蒿素（ART）对未成熟血吸虫有影响，而吡喹酮（PZQ）的作用主要针对成熟血吸虫，本研究调查了在携带 PZQ 不易感曼氏血吸虫分离株的小鼠中，ART 联合 PZQ 是否可能增强疗效。通过检测凋亡相关组织标志物 Fas（CD95）、抗凋亡（Bcl2）和血管生成[血管内皮生长因子（VEGF）]，研究了相关的血吸虫、炎症、肝组织病理学变化。将一批感染了 PZQ 不易感（EE10）曼氏血吸虫分离株的瑞士白化小鼠分为 12 组。第一组动物未经处理作为感染对照，而第二组至第六组动物接受递增剂量的 PZQ。第七组动物接受双倍剂量的 ART。第八组至第十二组动物接受 PZQ 和 ART 联合治疗，剂量和时间与第二组至第六组相同。评估了寄生虫学参数、肝功能以及 Fas、Bcl2 和 VEGF 抗体的组织病理学和免疫组织化学研究。ART 和 PZQ 联合给药降低了 PZQ 的 ED（50）（虫荷减少 50%的剂量）。单独使用 ART 和联合使用 PZQ 治疗的动物中未观察到典型的肉芽肿，FAS 和 VEGF 的表达最少，Bcl2 的表达增加。在同时接受 ART 和 PZQ 治疗的小鼠中记录到的最小组织病理学变化可能与 ART 的协同/附加作用有关，显著降低了感染强度。肝功能检查的改善支持在这种治疗方案下观察到的较轻的组织病理学变化。这项研究鼓励进行人体试验，特别是在疟疾非流行地区，并且应考虑到一些剂量方案中观察到的拮抗作用，研究不同的联合剂量。
