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.