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Sayed Hassan Seif el-Din	1 Article
Effect of Ketoconazole, a Cytochrome P450 Inhibitor, on the Efficacy of Quinine and Halofantrine against Schistosoma mansoni in Mice Sayed Hassan Seif el-Din, Abdel-Nasser Abdel-Aal Sabra, Olfat Ali Hammam, Naglaa Mohamed El-Lakkany Korean J Parasitol 2013;51(2):165-175. Published online April 25, 2013 DOI: https://doi.org/10.3347/kjp.2013.51.2.165 Abstract PDF The fear that schistosomes will become resistant to praziquantel (PZQ) motivates the search for alternatives to treat schistosomiasis. The antimalarials quinine (QN) and halofantrine (HF) possess moderate antischistosomal properties. The major metabolic pathway of QN and HF is through cytochrome P450 (CYP) 3A4. Accordingly, this study investigates the effects of CYP3A4 inhibitor, ketoconazole (KTZ), on the antischistosomal potential of these quinolines against Schistosoma mansoni infection by evaluating parasitological, histopathological, and biochemical parameters. Mice were classified into 7 groups: uninfected untreated (I), infected untreated (II), infected treated orally with PZQ (1,000 mg/kg) (III), QN (400 mg/kg) (IV), KTZ (10 mg/kg)+QN as group IV (V), HF (400 mg/kg) (VI), and KTZ (as group V)+HF (as group VI) (VII). KTZ plus QN or HF produced more inhibition (P<0.05) in hepatic CYP450 (85.7% and 83.8%) and CYT b5 (75.5% and 73.5%) activities, respectively, than in groups treated with QN or HF alone. This was accompanied with more reduction in female (89.0% and 79.3%), total worms (81.4% and 70.3%), and eggs burden (hepatic; 83.8%, 66.0% and intestinal; 68%, 64.5%), respectively, and encountering the granulomatous reaction to parasite eggs trapped in the liver. QN and HF significantly (P<0.05) elevated malondialdehyde levels when used alone or with KTZ. Meanwhile, KTZ plus QN or HF restored serum levels of ALT, albumin, and reduced hepatic glutathione (KTZ+HF) to their control values. KTZ enhanced the therapeutic antischistosomal potential of QN and HF over each drug alone. Moreover, the effect of KTZ+QN was more evident than KTZ+HF. Citations Citations to this article as recorded by Surface-grafted MoS₂ for ketoconazole sensing in biological and aqua samples Krishnapandi Alagumalai, Balamurugan Muthukutty, Mani Sivakumar, Daeho Lee, Seong-Cheol Kim Colloids and Surfaces A: Physicochemical and Engineering Aspects.2025; 706: 135808. CrossRef Indirect Modeling of Post-Prandial Intestinal Lymphatic Uptake of Halofantrine Using PBPK Approaches: Limitations and Implications Malaz Yousef, Farag E. S. Mosa, Khaled H. Barakat, Neal M. Davies, Raimar Löbenberg Pharmaceutics.2025; 17(9): 1228. CrossRef Anti-fibrotic Effect of Oral Versus Intraperitoneal Administration of Gold Nanoparticles in Hepatic Schistosoma mansoni-Infected Mice Shahira Abdelaziz Ali Ahmed, Samer Eid Mohamed Gad, Omima Mohamed Eida, Laila Mohamed Makhlouf Acta Parasitologica.2024; 69(1): 190. CrossRef Evaluation of the prophylactic and therapeutic efficacies of mucus and tissue nucleoproteins extracted from Biomphalaria alexandrina snails on schistosomiasis mansoni Esraa H. Nafie, Maha M. Abou-Gamra, Hanan S. Mossalem, Rania M. Sarhan, Olfat A. Hammam, Sami M. Nasr, Mona M. Anwar Journal of Parasitic Diseases.2024; 48(3): 551. CrossRef Screening and verification of CYP3A4 inhibitors from Bushen-Yizhi formula to enhance the bioavailability of osthole in rat plasma Jin-man Liu, Jun-mei Chen, Ming-jun Lin, Fan-chang Wu, Cui-ru Ma, Xue Zuo, Wen-qian Yu, Ming-jun Huang, Jian-song Fang, Wei-rong Li, Qi Wang, Yong Liang Journal of Ethnopharmacology.2022; 282: 114643. CrossRef The effect of ivermectin alone and in combination with cobicistat or elacridar in experimental Schistosoma mansoni infection in mice Belén Vicente, Julio López-Abán, Juliane Chaccour, Juan Hernández-Goenaga, Patricia Nicolas, Pedro Fernández-Soto, Antonio Muro, Carlos Chaccour Scientific Reports.2021;[Epub] CrossRef Lung cancer cells survive epidermal growth factor receptor tyrosine kinase inhibitor exposure through upregulation of cholesterol synthesis Mark C. Howell, Ryan Green, Roukiah Khalil, Elspeth Foran, Waise Quarni, Rajesh Nair, Stanley Stevens, Aleksandr Grinchuk, Andrew Hanna, Shyam Mohapatra, Subhra Mohapatra FASEB BioAdvances.2020; 2(2): 90. CrossRef Anti‐neurotoxic evaluation of synthetic and characterized metal complexes of thiosemicarbazone derivatives Fathy A. El‐Saied, Tarek A. Salem, Mohamad M.E. Shakdofa, Ahmed N. Al‐Hakimi Applied Organometallic Chemistry.2018;[Epub] CrossRef Anthelmintic activity of cytochrome P450 inhibitors miconazole and clotrimazole: in-vitro effect on the liver fluke Opisthorchis felineus Viatcheslav A. Mordvinov, Alexander G. Shilov, Maria Y. Pakharukova International Journal of Antimicrobial Agents.2017; 50(1): 97. CrossRef Cytochrome P450/ABC transporter inhibition simultaneously enhances ivermectin pharmacokinetics in the mammal host and pharmacodynamics in Anopheles gambiae Carlos J. Chaccour, Felix Hammann, Marta Alustiza, Sandra Castejon, Brian B. Tarimo, Gloria Abizanda, Ángel Irigoyen Barrio, Helena Martí Soler, Rafael Moncada, José Ignacio Bilbao, Azucena Aldaz, Marta Maia, José Luis Del Pozo Scientific Reports.2017;[Epub] CrossRef Dietary accumulation of tetrabromobisphenol A and its effects on the scallop Chlamys farreri Fengxiao Hu, Luqing Pan, Meng Xiu, Dong Liu Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology.2015; 167: 7. 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