Sabra Abdel-Nasser A, Salem Maha B, William Samia, Hammam Olfat A, El-Lakkany Naglaa M
Pharmacology Department, Theodor Bilharz Research Institute, 1 El-Nile St., Warrak El-Hadar, Imbaba, P.O. box 30, Giza, 12411, Egypt.
Parasitology Department, Theodor Bilharz Research Institute, 1 El-Nile St., Warrak El-Hadar, Imbaba, P.O. box 30, Giza, 12411, Egypt.
Sci Rep. 2025 Aug 7;15(1):28867. doi: 10.1038/s41598-025-14037-5.
Schistosomiasis, a prevalent tropical disease, possess public health challenges, with the standard treatment, praziquantel (PZQ), facing some limitations. Synriam (SYN), an antimalarial medication, has showed promises against schistosomiasis, although in vivo research on its efficacy in preventing infection-related consequences has not been thoroughly explored. This study looked at the effectiveness of SNY-PZQ combination treatment against Schistosoma mansoni in mice at various developmental phases, including juvenile (schistosomula) and mature stages. Worm load, egg deposition, parasite maturity, and liver histology were among the key outcomes evaluated. Their modulatory effects on liver injury indicators, proinflammatory cytokines, CYP450 enzymes, and apoptosis in mice infected with mature S. mansoni were also investigated. The study was divided into two experimental batches: schistosomula and mature stages, with infected mice from each batch divided into five groups to evaluate SNY, PZQ, and their combination. The SNY-PZQ combination was administered 3 weeks post-infection (PI) for schistosomula-stage infection, and 7 weeks PI for mature-stage infection. When SYN is combined with PZQ in their sub-curative doses (SC), it strengthens the worm killing effects, making it more potent than giving PZQ alone (SC), especially when the dual treatment was given against 7-weeks mature worms (95% vs. 76% for PZQ SC). This was accompanied with almost total eggs elimination and the repair of hepatic granulomatous lesions. Nevertheless, this combination therapy has moderate effectiveness (47% vs. 13% for PZQ SC) when given against 3-weeks juvenile worms. Furthermore, administering this combined therapy to 7-weeks mature worms reduces liver damage as evidenced by decreased oxidative stress, inflammation, and apoptosis, as well as normalization of liver serum enzymes, when compared to PZQ alone, implying that they may contribute to liver fibrosis prevention. Overall, SYN, when combined with PZQ, could improve treatment efficacy, potentially overcoming drug failures, offering a cost-effective strategy for managing schistosomiasis in resource-limited countries.
血吸虫病是一种流行的热带疾病，带来了公共卫生挑战，标准治疗药物吡喹酮（PZQ）存在一些局限性。抗疟药物Synriam（SYN）已显示出对血吸虫病的治疗前景，尽管其预防感染相关后果的体内研究尚未得到充分探索。本研究观察了SNY - PZQ联合治疗对不同发育阶段曼氏血吸虫的有效性，包括幼虫期（童虫）和成虫期。主要评估指标包括虫负荷、虫卵沉积、寄生虫成熟度和肝脏组织学。还研究了它们对感染成熟曼氏血吸虫小鼠的肝损伤指标、促炎细胞因子、CYP450酶和细胞凋亡的调节作用。该研究分为两个实验批次：童虫期和成虫期，每个批次的感染小鼠分为五组以评估SNY、PZQ及其组合。对于童虫期感染，在感染后3周（PI）给予SNY - PZQ联合治疗；对于成虫期感染，在感染后7周PI给予。当SYN与PZQ以亚治疗剂量（SC）联合使用时，可增强杀蠕虫效果，比单独给予PZQ（SC）更有效，特别是在针对7周龄成熟虫体进行双重治疗时（PZQ SC为76%，联合治疗为95%）。这伴随着几乎完全清除虫卵和修复肝脏肉芽肿病变。然而，针对3周龄幼虫给予这种联合治疗时效果中等（PZQ SC为13%，联合治疗为47%）。此外，与单独使用PZQ相比，对7周龄成熟虫体给予这种联合治疗可减少肝脏损伤，表现为氧化应激、炎症和细胞凋亡减少，以及肝脏血清酶正常化，这意味着它们可能有助于预防肝纤维化。总体而言，SYN与PZQ联合使用可提高治疗效果，可能克服药物失效问题，为资源有限国家管理血吸虫病提供一种具有成本效益的策略。
