title: Evaluation of the inhibitory effects of miltefosine on the growth of Babesia and Theileria parasites.
abstract: Miltefosine, a membrane-active synthetic ether-lipid analogue, has antiproliferative and antiparasitic effects. In this study, the inhibitory effects of miltefosine were evaluated against three Babesia species and Theileria equi in vitro and against Babesia microti in mice. The drug showed significant growth inhibition from an initial parasitemia of 1% for Babesia bovis, Babesia bigemina, Babesia caballi, and T. equi with IC50 values of 25, 10.2, 10.4, and 99 μM, respectively. Complete inhibition was observed at 200 μM of miltefosine on the third day of culture for the three Babesia species and 400 μM on the fourth day for T. equi. Reverse-transcription PCR (RT-PCR) showed that miltefosine inhibited the transcription of choline-phosphate cytidylyltransferase in B. bovis. Miltefosine at a dose rate of 30 mg/kg resulted in a 71.7% inhibition of B. microti growth in BALB/c mice. Miltefosine might be used for drug therapy in babesiosis.
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan; Department of Parasitology, Faculty of Veterinary Medicine, University of Sadat City, Sadat City 32897, Minoufiya, Egypt.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: AbouLaila
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan.
authors.forename: Davasorin
authors.initials: D
authors.lastname: Batadoj
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan; Department of Infectious Diseases and Internal Medicine, Faculty of Veterinary Medicine, University of Sadat City, Sadat City 32897, Minoufiya, Egypt.
authors.forename: Akram
authors.initials: A
authors.lastname: Salama
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan.
authors.forename: Tserendorj
authors.initials: T
authors.lastname: Munkhjargal
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan.
authors.forename: Madoka
authors.initials: M
authors.lastname: Ichikawa-Seki
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan.
authors.forename: Mohammad
authors.initials: M
authors.lastname: A Terkawi
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan.
authors.forename: Naoaki
authors.initials: N
authors.lastname: Yokoyama
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan. Electronic address: igarcpmi@obihiro.ac.jp.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Igarashi
mesh_terms: D000818:Animals; D000977:Antiparasitic Agents / Q000627:therapeutic use*; D001403:Babesia / Q000187:drug effects* / Q000254:growth & development; D001404:Babesiosis / Q000188:drug therapy* / Q000469:parasitology; D019916:Choline-Phosphate Cytidylyltransferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D018512:Parasitemia / Q000662:veterinary; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction / Q000662:veterinary; D016794:Theileria / Q000187:drug effects* / Q000254:growth & development; D013801:Theileriasis / Q000188:drug therapy* / Q000469:parasitology
chemical_list: D000977:Antiparasitic Agents; D015800:Protozoan Proteins; D010767:Phosphorylcholine; C039128:miltefosine; D019916:Choline-Phosphate Cytidylyltransferase
keywords: Babesia; Choline-phosphate cytidylyltransferase; In vitro; In vivo; Miltefosine; Transcription