In vitro and in vivo effects of the phytohormone inhibitor fluridone against Neospora caninum infection |
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| Affiliation: | 1. National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan;2. Biology and Environmental Studies Program, University of the Philippines Cebu, Gorordo Avenue, Lahug, Cebu City 6000, Philippines;3. Department of Parasitology, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo 162-8640, Japan;4. Graduate School of Life and Environmental Studies, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan;5. RIKEN Center for Sustainable Resource Science, 1-7-22, Suehiro, Tsurumi, Yokohama 230-0045, Japan;6. Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan;1. National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan;2. Faculty of Veterinary Science (The Establishment Project), Prince of Songkla University, Hatyai, Songkhla 90110, Thailand;3. Biology and Environmental Studies Program, Sciences Cluster, University of the Philippines Cebu, Lahug, Cebu City, Philippines;1. School of Veterinary and Life Sciences, Murdoch University, Murdoch, Perth, WA 6150, Australia;2. CAPES Foundation, Ministry of Education of Brazil, Brasília, DF 70040-020, Brazil;3. The Australia Zoo Hospital, Beerwah, Qld 4519, Australia;4. School of Veterinary Science, University of Queensland, St. Lucia, Qld 4072, Australia |
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| 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 ± 43.96 μM and 330.6 ± 52.38 μM, respectively). However, FLU did not affect parasite replication at 24 h 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 15 days. 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. |
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