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Cited by 79Trypanosoma species research and implicationsResearch on Leishmaniasis StudiesVector-borne infectious diseases

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The efficacy of ascofuranone in a consecutive treatment on Trypanosoma brucei brucei in mice

Yabu, Yoshisada, Yoshida, Ayako, Suzuki, Takashi, Nihei, Coh-ichi, Kawai, Keisuke, Minagawa, Nobuko, Hosokawa, Tomoyoshi, Nagai, Kazuo, Kita, Kiyoshi, Ohta, Nobuo·2003·Parasitology International
DOI 10.1016/s1383-5769(03)00012-6
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Abstract

Consecutive administration of ascofuranone without glycerol was found to have therapeutic efficacy against Trypanosoma brucei brucei infection in mice. A suspension of ascofuranone (25-100 mg/kg) was administrated intraperitoneally every 24 h for 1-4 consecutive days to trypanosome-infected mice and efficacy was compared with oral treatment. With intraperitoneal administration, all mice treated with 100 mg/kg ascofuranone for 4 consecutive days were cured. On contrary, with oral treatment a higher dose of ascofuranone (400 mg/kg) was needed for 8 consecutive days to cure the mice. With intraperitoneal treatment, parasitemia was strongly suppressed, with almost all long slender bloodstream forms of the parasite changed to short stumpy forms by day 3 and the parasites have been eliminated 4 days after the start of treatment. These ascofuranone-induced short stumpy forms were morphologically analogous to the stumpy forms 2 days after peak parasitemia of pleomorphic clone of T. b. brucei GUTat 3.1. However, the properties of ubiquinol oxidase activity, which is the target of ascofuranone, in mitochondria isolated from before and after treatment, were almost same. The enzymatic activities of ubiquinol oxidase were only decreased to approximately 30% within a day after treatment, and then kept at nearly the same level. In the present study, we have improved regimen for administration of ascofuranone without glycerol, and demonstrated that consecutively administrated ascofuranone showed trypanocidal effects in T. b. brucei infected mice. Our present results strongly suggest that consecutive administration of ascofuranone may be an effective chemotherapy for African trypanosomiasis.

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Metadata

Authors
Yabu, Y., Yoshida, A., Suzuki, T., Nihei, C.-I., Kawai, K., Minagawa, N., Hosokawa, T., Nagai, K., Kita, K., & Ohta, N.
Affiliations
  • Nagoya City University (JP)
  • The University of Tokyo (JP)
  • Niigata University of Pharmacy and Medical and Life Sciences (JP)
  • Chubu University (JP)
Corresponding author
Yabu, Yoshisada
ORCID
Venue
Parasitology International
Publisher
Elsevier BV
Published
2003-06
Volume
52
Issue
2
Pages
155-164
ISSN
1383-5769 (ISSN-L)
DOI
10.1016/s1383-5769(03)00012-6
OpenAlex
W2077284199
Cited by
79
References
43
Citations by year
2024: 4 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 4 · 2019: 5 · 2018: 6 · 2017: 3 · 2016: 5 · 2015: 4 · 2014: 4 · 2013: 5 · 2012: 3
FWCI
1.93
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Parasitology International (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Trypanosoma species research and implications
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Research on Leishmaniasis Studies
  • Life Sciences › Immunology and Microbiology › Parasitology › Vector-borne infectious diseases
Keywords
ascofuranone, Trypanosoma brucei brucei, sleeping sickness, trypanocidal activity, intraperitoneal administration, oral administration, parasitemia reduction, ubiquinol oxidase, chemotherapy
MeSH terms
Administration, Oral, Animals, Antiprotozoal Agents, Drug Administration Schedule, Female, Injections, Intraperitoneal, Mice, Inbred C57BL, Models, Molecular, Oxidoreductases, Sesquiterpenes, Trypanosoma brucei brucei, Trypanosomiasis, African, Mice

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