Evaluation of methylene blue, pyrimethamine and its combination on an in vitro Neospora caninum model

Neospora caninum is an apicomplexan parasite strongly related to reproductive problems in cattle. The neosporosis control is not well established and several fronts are under development, predominantly based on immune protection, immunomodulation and chemotherapy. The use of anti-malarial drugs as t...

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Bibliographic Details
Published in:Parasitology 2017-05, Vol.144 (6), p.827-833
Main Authors: PEREIRA, LUIZ MIGUEL, VIGATO-FERREIRA, ISABEL CRISTINA, DE LUCA, GABRIELA, BRONZON DA COSTA, CÁSSIA MARIANA, YATSUDA, ANA PATRÍCIA
Format: Article
Language:English
Subjects:
Animals
Antimalarials - pharmacology
Antimalarials - therapeutic use
Antimalarials - toxicity
Cercopithecus aethiops
Chemotherapy
Chromatography
Coccidiosis - drug therapy
Cytotoxicity
Drugs
Enzyme Inhibitors - pharmacology
Enzyme Inhibitors - therapeutic use
Enzyme Inhibitors - toxicity
Ethanol
Immune clearance
Immunomodulation
Immunosuppressive agents
In vitro methods and tests
Infections
Inhibitory Concentration 50
Malaria
Methylene blue
Methylene Blue - pharmacology
Methylene Blue - therapeutic use
Methylene Blue - toxicity
Neospora - drug effects
Neosporosis
Neurosciences
Parasites
Parasitology
Pyrimethamine
Pyrimethamine - pharmacology
Pyrimethamine - therapeutic use
Pyrimethamine - toxicity
Tachyzoites
Vaccines
Vector-borne diseases
Vero Cells - drug effects
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Summary:Neospora caninum is an apicomplexan parasite strongly related to reproductive problems in cattle. The neosporosis control is not well established and several fronts are under development, predominantly based on immune protection, immunomodulation and chemotherapy. The use of anti-malarial drugs as therapeutic sources has, in theory, considerable potential for any apicomplexan. Drugs such as methylene blue (MB) and pyrimethamine (Pyr) represent therapeutic options for malaria; thus, their use for neosporosis should be assessed. In this work, we tested the effects of MB and Pyr on N. caninum proliferation and clearance, using LacZ-tagged tachyzoites. The drugs inhibited at nanomolar dosages and its combination demonstrated an antagonistic interaction in proliferation assays, according to the Chou and Talalay method for drug combination index. However, the drug combination significantly improved the parasite in vitro clearance. The repositioning of well-established drugs opens a short-term strategy to obtain low-cost therapeutics approaches against neosporosis.
ISSN:0031-1820
1469-8161
DOI:10.1017/S0031182016002584