Schistosomiasis is a chronic disease caused by blood flukes of the Schistosoma spp. New approaches against this morbid infection are needed. In this study, we investigated fluconazole (FLZ) as an inhibitor of Schistosoma mansoni cytochrome P450 (S. mansoni CYP450) enzyme at different life cycle stages. We compared FLZ (10 mg/kg for two days) effects when administrated early 5 days post-infection (dpi) (Early I) and 21 dpi (Early II) versus late administration 60 dpi on S. mansoni CYP450 gene expression. These different FLZ treatment regimens were evaluated in experimentally infected mice with S. mansoni. This study showed that administration of FLZ, whether early or late during schistosomal infection, resulted in significant inhibition of S. mansoni CYP450 expression in the adult stage (P < 0.001). Early exposure to FLZ during the first week of infection significantly decreased the number of schistosomula that reached the adult stage compared to the infected control group and resulted in significant inhibition of S. mansoni CYP450 expression (P < 0.001) in the adult stage. In the Early I group, the fewest number of eggs per liver tissue gram was recorded. Our data suggested that FLZ is a S. mansoni CYP450 gene expression inhibitor with greater effect on schistosomula stages.
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http://dx.doi.org/10.1016/j.exppara.2022.108291 | DOI Listing |
Sci Rep
May 2024
Department of Global Public Health, Karolinska Institutet, Karolinska University Hospital, Tomtebodavägen 18A, 171 77, Stockholm, Sweden.
Metabolism of praziquantel (PZQ), a racemic mixture and the only drug approved to treat S. mansoni infection, is mediated by genetically polymorphic enzymes. Periodic school-based mass drug administration (MDA) with PZQ is the core intervention to control schistosomiasis.
View Article and Find Full Text PDFJ Helminthol
February 2023
Department of Medical Parasitology, Faculty of Medicine, Mansoura University, 2 El Gomhouria Street, Mansoura 35516, Egypt.
Biochanin A (BCA) is a multifunctional natural compound that possesses anti-infective, anti-inflammatory, anti-oxidative and hepatoprotective effects. The aim of the study was to assess the therapeutic efficacy of BCA on -infected mice. Fifty mice were divided into six different groups as non-infected, non-infected BCA-treated, infected untreated, early infected BCA-treated (seven days post-infection (dpi)), late infected BCA-treated 60 dpi and infected praziquantel (PZQ)-treated groups.
View Article and Find Full Text PDFExp Parasitol
August 2022
Professor of Pharmacology, Theodor Bilharz Research Institute, Giza, Egypt. Electronic address:
Treatment of schistosomiasis is heavily reliant on the single antischistosomal drug praziquantel (PZQ). The use of synergistic drug-drug interactions is one possible solution, which could be used to mitigate PZQ's poor and variable bioavailability. Itraconazole (ITZ), a triazole antifungal agent, is a potent CYP3A inhibitor that can cause significant drug-drug interactions when used with CYP3A substrates.
View Article and Find Full Text PDFExp Parasitol
August 2022
Department of Medical Parasitology, Faculty of Medicine, Mansoura University, Egypt.
Schistosomiasis is a chronic disease caused by blood flukes of the Schistosoma spp. New approaches against this morbid infection are needed. In this study, we investigated fluconazole (FLZ) as an inhibitor of Schistosoma mansoni cytochrome P450 (S.
View Article and Find Full Text PDFSci Rep
February 2021
Clinica Universidad de Navarra, Pamplona, Spain.
Schistosoma mansoni is less susceptible to the antiparasitic drug ivermectin than other helminths. By inhibiting the P-glycoprotein or cytochrome P450 3A in mice host or parasites in a murine model, we aimed at increasing the sensitivity of S. mansoni to the drug and thus preventing infection.
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