دورية أكاديمية
أعرض في EDS

Itraconazole, a cytochrome P450 inhibitor, enhanced the efficacy of praziquantel against Schistosoma mansoni infection and alleviated liver injury in mice.

التفاصيل البيبلوغرافية
العنوان: Itraconazole, a cytochrome P450 inhibitor, enhanced the efficacy of praziquantel against Schistosoma mansoni infection and alleviated liver injury in mice.
المؤلفون: Sabra AA; Professor of Pharmacology, Theodor Bilharz Research Institute, Giza, Egypt. Electronic address: abdelnassersabraa@yahoo.com., Salem MB; Lecturer of Pharmacology, Theodor Bilharz Research Institute, Giza, Egypt. Electronic address: m.salem@tbri.gov.eg., William S; Professor of Parasitology, Theodor Bilharz Research Institute, Giza, Egypt. Electronic address: samiaw2006@yahoo.com., Hammam OA; Professor of Pathology, Theodor Bilharz Research Institute, Giza, Egypt. Electronic address: totoali1@hotmail.com., El-Lakkany NM; Professor of Pharmacology, Theodor Bilharz Research Institute, Giza, Egypt. Electronic address: n.ellakkany@tbri.gov.eg.
المصدر: Experimental parasitology [Exp Parasitol] 2022 Aug; Vol. 239, pp. 108293. Date of Electronic Publication: 2022 Jun 03.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Academic Press Country of Publication: United States NLM ID: 0370713 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2449 (Electronic) Linking ISSN: 00144894 NLM ISO Abbreviation: Exp Parasitol Subsets: MEDLINE
أسماء مطبوعة: Publication: Orlando, FL : Academic Press
Original Publication: New York.
مواضيع طبية MeSH: Anthelmintics*/pharmacology , Anthelmintics*/therapeutic use , Schistosomiasis mansoni*/drug therapy , Schistosomiasis mansoni*/pathology, Animals ; Itraconazole/pharmacology ; Itraconazole/therapeutic use ; Liver/pathology ; Mice ; Praziquantel/pharmacology ; Praziquantel/therapeutic use ; Schistosoma mansoni
مستخلص: 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. This study investigates the effect of ITZ as adjuvant therapy with PZQ on worm load, egg deposition and maturation, and the consequent histopathology and biochemical abnormalities in the liver during the immature and mature stages of Schistosoma mansoni (S. mansoni) infection. S. mansoni-infected mice were divided into five groups of eight-ten mice each: (I) infected untreated, (II) infected and treated with PZQ 3 weeks PI, (III) infected and treated with both ITZ and PZQ 3 weeks PI, (IV) infected and treated with PZQ 7 weeks PI, and (V) infected and treated with both ITZ and PZQ 7 weeks PI. All mice were killed by rapid decapitation 9 weeks PI. Data revealed that ITZ in combination with PZQ at both immature and mature stages improved the parasitological criteria of cure, and greatly reduced inflammation, granuloma and fibrotic tissue formation, and apoptosis versus PZQ alone. Furthermore, it showed the greatest impact on improving liver injury and oxidative stress markers. Notably, the effect was considerably stronger at the mature stage of S. mansoni infection. These findings support the notion that ITZ increased PZQ's antischistosomal activity by inhibiting CYP450 expression, potentially reducing PZQ metabolism and increasing systemic exposure.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
فهرسة مساهمة: Keywords: CYP450; Caspase 3; Granuloma; Itraconazole; Praziquantal; Schistosoma mansoni
المشرفين على المادة: 0 (Anthelmintics)
304NUG5GF4 (Itraconazole)
6490C9U457 (Praziquantel)
تواريخ الأحداث: Date Created: 20220606 Date Completed: 20220719 Latest Revision: 20220719
رمز التحديث: 20240628
DOI: 10.1016/j.exppara.2022.108293
PMID: 35667394
قاعدة البيانات: MEDLINE
الوصف
تدمد:1090-2449
DOI:10.1016/j.exppara.2022.108293