RT Journal Article
T1 Buparvaquone is active against Neospora caninum in vitro and in experimentally infected mice
A1 Müller, Joachim
A1 Aguado-Martinez, Adriana
A1 Manser, Vera
A1 Balmer, Vreni
A1 Winzer, Pablo
A1 Ritler, Dominic
A1 Hostettler, Isabel
A1 Arranz Solís, David
A1 Ortega Mora, Luis Miguel
A1 Hemphill, Andrew
AB The naphthoquinone buparvaquone is currently the only drug used against theileriosis. Here, the effects of buparvaquone were investigated in vitro and in an experimental mouse model for Neospora caninum infection. In 4-day proliferation assays, buparvaquone efficiently inhibited N. caninum tachyzoite replication (IC50 = 4.9 nM; IC100 = 100 nM). However, in the long term tachyzoites adapted and resumed proliferation in the presence of 100 nM buparvaquone after 20 days of cultivation. Parasiticidal activity was noted after 9 days of culture in 0.5 µM or 6 days in 1 µM buparvaquone. TEM of N. caninum infected fibroblasts treated with 1 µM buparvaquone showed that the drug acted rather slowly, and ultrastructural changes were evident only after 3–5 days of treatment, including severe alterations in the parasite cytoplasm, changes in the composition of the parasitophorous vacuole matrix and a diminished integrity of the vacuole membrane. Treatment of N. caninum infected mice with buparvaquone (100 mg/kg) either by intraperitoneal injection or gavage prevented neosporosis symptoms in 4 out of 6 mice in the intraperitoneally treated group, and in 6 out of 7 mice in the group receiving oral treatment. In the corresponding controls, all 6 mice injected intraperitoneally with corn oil alone died of acute neosporosis, and 4 out of 6 mice died in the orally treated control group. Assessment of infection intensities in the treatment groups showed that, compared to the drug treated groups, the controls showed a significantly higher parasite load in the lungs while cerebral parasite load was higher in the buparvaquone-treated groups. Thus, although buparvaquone did not eliminate the parasites infecting the CNS, the drug represents an interesting lead with the potential to eliminate, or at least diminish, fetal infection during pregnancy.
PB Elsevier
SN 2211-3207
YR 2015
FD 2015-02-13
LK https://hdl.handle.net/20.500.14352/91748
UL https://hdl.handle.net/20.500.14352/91748
LA eng
NO Müller, J., Aguado-Martinez, A., Manser, V., Balmer, V., Winzer, P., Ritler, D., Hostettler, I., Arranz-Solís, D., Ortega-Mora, L., & Hemphill, A. (2015). Buparvaquone is active against Neospora caninum in vitro and in experimentally infected mice. International journal for parasitology. Drugs and drug resistance, 5(1), 16–25. https://doi.org/10.1016/j.ijpddr.2015.02.001
NO National Science Foundation
NO Vetsuisse Faculty of the University of Bern
DS Docta Complutense
RD 11 abr 2025