Optimizing the therapeutic benefits of synriam combined with praziquantel in mice harbouring juvenile and mature Schistosoma mansoni

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Sabra A.-N.A.; Salem M.B.; William S.; Hammam O.A.; El-Lakkany N.M.

Journal: Scientific Reports

Publisher: Nature Research

Publication Date: 7 August 2025

Volume / Issue: Volume 15 / Issue 1

Article No.: 28867

ISSN: 20452322

DOI: 10.1038/s41598-025-14037-5

Scopus: View on Scopus

PubMed: 40775423

Document Type: Article

Access: All Open Access; Gold Open Access; Green Open Access


Authors and Affiliations

Sabra A.-N.A., Pharmacology Department, Theodor Bilharz Research Institute, P.O. box 30, 1 El-Nile St., Warrak El-Hadar, Imbaba, Giza, 12411, Egypt; Salem M.B., Pharmacology Department, Theodor Bilharz Research Institute, P.O. box 30, 1 El-Nile St., Warrak El-Hadar, Imbaba, Giza, 12411, Egypt; William S., Parasitology Department, Theodor Bilharz Research Institute, P.O. box 30, 1 El-Nile St., Warrak El-Hadar, Imbaba, Giza, 12411, Egypt; Hammam O.A., Pathology Department, Theodor Bilharz Research Institute, P.O. box 30, 1 El-Nile St., Warrak El-Hadar, Imbaba, Giza, 12411, Egypt; El-Lakkany N.M., Pharmacology Department, Theodor Bilharz Research Institute, P.O. box 30, 1 El-Nile St., Warrak El-Hadar, Imbaba, Giza, 12411, Egypt


Abstract

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. © The Author(s) 2025.


Keywords

Apoptosis; CYP450; Granuloma; Inflammation; Praziquantal; Schistosoma mansoni; Synriam; Animals; Anthelmintics; Cytokines; Disease Models, Animal; Drug Therapy, Combination; Female; Liver; Male; Mice; Praziquantel; Schistosomiasis mansoni; anthelmintic agent; cytokine; animal; combination drug therapy; disease model; drug effect; drug therapy; metabolism; mouse; parasitology; pathology


Citation Information

Scopus Citations: 3


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