Pereira Luiz Miguel, Vigato-Ferreira Isabel Cristina, DE Luca Gabriela, Bronzon DA Costa Cássia Mariana, Yatsuda Ana Patrícia
Faculdade de Ciências Farmacêuticas de Ribeirão Preto,Universidade de São Paulo,Av do Café,s/n,14040-903,Ribeirão Preto,SP,Brazil.
Parasitology. 2017 May;144(6):827-833. doi: 10.1017/S0031182016002584. Epub 2017 Jan 11.
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.
犬新孢子虫是一种与牛的生殖问题密切相关的顶复门寄生虫。新孢子虫病的防控措施尚未完善，目前有几个方面正在研究中，主要基于免疫保护、免疫调节和化疗。理论上，使用抗疟药物作为治疗手段对任何顶复门寄生虫都具有相当大的潜力。亚甲蓝（MB）和乙胺嘧啶（Pyr）等药物是治疗疟疾的选择；因此，应评估它们在新孢子虫病治疗中的应用。在这项研究中，我们使用LacZ标记的速殖子测试了MB和Pyr对犬新孢子虫增殖和清除的影响。根据Chou和Talalay的药物联合指数方法，这些药物在纳摩尔剂量下具有抑制作用，并且它们的组合在增殖试验中表现出拮抗作用。然而，药物组合显著提高了体外寄生虫清除率。重新利用已有的药物为获得低成本的新孢子虫病治疗方法开辟了一条短期策略。
