In vivo preliminary investigations of the effects of the benzimidazole anthelmintic drug flubendazole on rat embryos and fetuses |
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| Affiliation: | 1. Accelera S.r.l., Viale Pasteur 10, 20014 Nerviano (MI), Italy;3. Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, USA;4. Institute of Parasitology, McGill University, Montreal, Canada;5. AbbVie Inc., 1 North Waukegan Road, North Chicago, IL 60064, USA;6. Independent Consultant, Aux Fermes de Bosne, F 39230 Mantry, France;1. Laboratory of Reproduction and Metabolism, CEFYBO-CONICET, School of Medicine, University of Buenos Aires, Paraguay 2155, 17th floor, 1121ABG Buenos Aires, Argentina;2. Department of Biological Chemistry, School of Natural Sciences, University of Buenos Aires, Intendente Guiraldes 2160, C1428EGA Buenos Aires, Argentina;1. Laboratório de Doenças Parasitárias, Escola de Medicina & Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Campus Universitário Morro do Cruzeiro, Ouro Preto, MG 35400-000, Brazil;2. Laboratório de Parasitologia Básica, Departamento de Patologia e Parasitologia Básica, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Alfenas, MG 37130-001, Brazil;3. Laboratório de Desenvolvimento Galênico e Nanotecnologia (LDGNano) – CiPharma, Escola de Farmácia, Universidade Federal de Ouro Preto, Minas Gerais 35400-000, Brazil;4. Drugs for Neglected Disease initiative, 1202 Geneva, Switzerland;1. University of Milan School of Medicine, Milan, Italy;2. University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania;3. Pathology, Yonsei University College of Medicine, Seoul, South Korea;4. Humanitas Clinical and Research Center, Hepatobiliary and General Surgery, Rozzano, Milano, Italy;5. Humanitas Clinical and Research Center, Biostatistics Unit, Rozzano, Milano, Italy;6. Pathology, Fondazione IRCCS Ca'' Granda Ospedale Policlinico, Milan, Italy;7. Hepato-Gastroenterology and Digestive Oncology, Saint André Hospital CHU Bordeaux and Inserm UMR 1053, Bordeaux University, Bordeaux, France;8. Pathology, University of Washington School of Medicine, Seattle, WA, USA;9. Pathology, CHU de Bordeaux, Pellegrin Hospital, Bordeaux, France and Inserm UMR 1053, Bordeaux University, Bordeaux, France;10. Humanitas Clinical and Research Center, Pathology Unit, Rozzano, Milano, Italy;11. Humanitas University, Department of Biomedical Sciences, Rozzano, Milano, Italy;1. Department of Physiology & Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA;2. Interdisciplinary Toxicology Program, University of Georgia, Athens, GA 30602, USA |
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| Abstract: | Flubendazole, in a new formulation with high systemic bioavailability, has been proposed as a macrofilaricide against filarial diseases.To investigate embryotoxic activity, the new flubendazole formulation was administered orally to Sprague Dawley rats at 2, 3.46, 6.32 mg/kg/day on gestation day (GD) 9.5 and 10.5. Embryos/fetuses were evaluated on GD 11.5, 12.5 or 20.At 6.32 mg/kg/day (Cmax = 0.801 μg/mL after single administration), flubendazole initially induced an arrest of embryonic development followed by a generalized cell death that led to 100% embryolethality by GD 12.5.At 3.46 mg/kg/day (Cmax = 0.539 μg/mL after single administration), flubendazole markedly reduced embryonic development by GD 12.5 without causing cell death. On GD 20, 80% of fetuses showed malformations.At 2 mg/kg/day (Cmax = 0.389 μg/mL after single administration), it did not interfere with rat embryofetal development. |
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| Keywords: | Flubendazole Filarial diseases Benzimidazole anthelmintic Embryolethality Teratogenicity Eye development |
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