Therapeutic efficacy of candidate antischistosomal drugs in a murine model of schistosomiasis mansoni

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Mohammad O.S.; Hussein H.M.; Abdel-Sayed S.W.; Mohamed G.A.; Shehata M.A.S.

Journal: Parasitology Research

Publisher: Springer Science and Business Media Deutschland GmbH

Publication Date: 21 May 2024

Volume / Issue: Volume 123 / Issue 5

Article No.: 215

ISSN: 9320113

DOI: 10.1007/s00436-024-08236-8

Scopus: View on Scopus

PubMed: 38771511

Document Type: Article

Authors and Affiliations

Mohammad O.S., Medical Parasitology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt; Hussein H.M., Medical Parasitology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt; Abdel-Sayed S.W., Parasitology Department, Theodor Bilharz Research Institute, Giza, Egypt; Mohamed G.A., Medical Parasitology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt; Shehata M.A.S., Medical Parasitology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt

Abstract

Schistosomiasis is a neglected tropical disease associated with considerable morbidity. Praziquantel (PZQ) is effective against adult schistosomes, yet, it has little effect on juvenile stages, and PZQ resistance is emerging. Adopting the drug repurposing strategy as well as assuming enhancing the efficacy and lessening the doses and side effects, the present study aimed to investigate the in vivo therapeutic efficacy of the widely used antiarrhythmic, amiodarone, and diuretic, spironolactone, and combinations of them compared to PZQ. Mice were infected by Schistosoma mansoni “S. mansoni” cercariae (Egyptian strain), then they were divided into two major groups: Early- [3 weeks post-infection (wpi)] and late- [6 wpi] treated. Each group was subdivided into seven subgroups: positive control, PZQ, amiodarone, spironolactone, PZQ combined with amiodarone, PZQ combined with spironolactone, and amiodarone combined with spironolactone-treated groups. Among the early-treated groups, spironolactone had the best therapeutic impact indicated by a 69.4% reduction of total worm burden (TWB), 38.6% and 48.4% reduction of liver and intestine egg load, and a significant reduction of liver granuloma number by 49%. Whereas, among the late-treated groups, amiodarone combined with PZQ was superior to PZQ alone evidenced by 96.1% reduction of TWB with the total disappearance of female and copula in the liver and intestine, 53.1% and 84.9% reduction of liver and intestine egg load, and a significant reduction of liver granuloma number by 67.6%. Comparatively, spironolactone was superior to PZQ and amiodarone in the early treatment phase targeting immature stages, while amiodarone had a more potent effect when combined with PZQ in the late treatment phase targeting mature schistosomes. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2024.

Keywords

Amiodarone; Drug repurposing; Praziquantel; Schistosoma mansoni; Spironolactone; Animals; Anthelmintics; Disease Models, Animal; Drug Therapy, Combination; Female; Liver; Male; Mice; Schistosomiasis mansoni; Schistosomicides; Treatment Outcome; spectone; anthelmintic agent; antischistosomal agent; adult; animal cell; animal experiment; animal model; animal tissue; Article; cercaria; controlled study; developmental stage; drug efficacy; drug repositioning; giant cell; granuloma; histopathology; intestine tissue; liver granuloma; liver necrosis; liver tissue; mesentery blood vessel; mitochondrial membrane potential; mouse; nonhuman; ovum; parasite egg count; worm burden; animal; combination drug therapy; disease model; drug effect; drug therapy; parasitology

Citation Information

Scopus Citations: 2

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