title: In vitro and in vivo effects of the phytohormone inhibitor fluridone against Neospora caninum infection.
abstract: Neospora caninum causes abortion and stillbirth in cattle. Identification of effective drugs against this parasite remains a challenge. Previous studies have suggested that disruption of abscisic acid (ABA)-mediated signaling in apicomplexan parasites such as Toxoplasma gondii offers a new drug target. In this study, the ABA inhibitor, fluridone (FLU), was evaluated for its action against N. caninum. Production of endogenous ABA within N. caninum was confirmed by ultra-performance liquid chromatography-tandem quadruple mass spectrometry. Subsequently, FLU treatment efficacy was assessed using in vitro. Results revealed that FLU inhibited the growth of N. caninum and T. gondii in vitro (IC50 143.1±43.96μM and 330.6±52.38μM, respectively). However, FLU did not affect parasite replication at 24h post-infection, but inhibited egress of N. caninum thereafter. To evaluate the effect of FLU in vivo, N. caninum-infected mice were treated with FLU for 15days. FLU treatment appeared to ameliorate acute neosporosis induced by lethal parasite challenge. Together, our data shows that ABA might control egress in N. caninum. Therefore, FLU has potential as a candidate drug for the treatment of acute neosporosis.
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan; Biology and Environmental Studies Program, University of the Philippines Cebu, Gorordo Avenue, Lahug, Cebu City 6000, Philippines.
authors.forename: Rochelle Haidee D
authors.initials: RH
authors.lastname: Ybañez
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan.
authors.forename: Arpron
authors.initials: A
authors.lastname: Leesombun
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Nishimura
authors.affiliation: Department of Parasitology, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Graduate School of Life and Environmental Studies, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan.
authors.forename: Ryuma
authors.initials: R
authors.lastname: Matsubara
authors.affiliation: RIKEN Center for Sustainable Resource Science, 1-7-22, Suehiro, Tsurumi, Yokohama 230-0045, Japan.
authors.forename: Mikiko
authors.initials: M
authors.lastname: Kojima
authors.affiliation: RIKEN Center for Sustainable Resource Science, 1-7-22, Suehiro, Tsurumi, Yokohama 230-0045, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sakakibara
authors.affiliation: Department of Parasitology, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan.
authors.forename: Kisaburo
authors.initials: K
authors.lastname: Nagamune
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan. Electronic address: nisikawa@obihiro.ac.jp.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Nishikawa
mesh_terms: D000040:Abscisic Acid / Q000037:antagonists & inhibitors*; D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000188:drug therapy* / Q000469:parasitology; D003048:Coccidiosis / Q000188:drug therapy* / Q000469:parasitology; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D018688:Neospora / Q000187:drug effects*; D010937:Plant Growth Regulators / Q000037:antagonists & inhibitors*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000662:veterinary*; D011728:Pyridones / Q000494:pharmacology*; D013047:Specific Pathogen-Free Organisms; D050497:Stillbirth / Q000662:veterinary
chemical_list: D010937:Plant Growth Regulators; D011728:Pyridones; C013351:fluridone; D000040:Abscisic Acid
keywords: Abscisic acid; Fluridone; Neospora caninum