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Inhibitory action of phenothiazinium dyes against Neospora caninum.

Pereira, LM, Mota, CM, Baroni, L, Bronzon da Costa, CM, Brochi, JCV, Wainwright, M, Mineo, TWP, Braga, GÚL and Yatsuda, AP (2020) Inhibitory action of phenothiazinium dyes against Neospora caninum. Scientific Reports, 10 (1). ISSN 2045-2322

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Abstract

Neospora caninum is an Apicomplexan parasite related to important losses in livestock, causing abortions and decreased fertility in affected cows. Several chemotherapeutic strategies have been developed for disease control; however, no commercial treatment is available. Among the candidate drugs against neosporosis, phenothiazinium dyes, offer a low cost-efficient approach to parasite control. We report the anti-parasitic effects of the phenothiaziums Methylene Blue (MB), New Methylene Blue (NMB), 1,9-Dimethyl Methylene Blue (DMMB) and Toluidine Blue O (TBO) on N. caninum, using in vitro and in vivo models. The dyes inhibited parasite proliferation at nanomolar concentrations (0.019-1.83 μM) and a synergistic effect was achieved when Methylene Blue was combined with New Methylene Blue (Combination Index = 0.84). Moreover, the phenothiazinium dyes improved parasite clearance when combined with Pyrimethamine (Pyr). Combination of Methylene Blue + 1,9-Dimethyl Methylene Blue demonstrated superior efficacy compared to Pyrimethamine based counterparts in an in vivo model of infection. We also observed that Methylene Blue, New Methylene Blue and 1,9-Dimethyl Methylene Blue increased by 5000% the reactive oxygen species (ROS) levels in N. caninum tachyzoites. Phenothiazinium dyes represent an accessible group of candidates with the potential to compound future formulations for neosporosis control.

Item Type: Article
Uncontrolled Keywords: 0601 Biochemistry and Cell Biology, 0299 Other Physical Sciences
Subjects: R Medicine > RM Therapeutics. Pharmacology
R Medicine > RV Botanic, Thomsonian, and eclectic medicine
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Nature Publishing Group
Related URLs:
Date Deposited: 11 May 2020 11:27
Last Modified: 11 May 2020 11:30
DOI or Identification number: 10.1038/s41598-020-64454-x
URI: http://researchonline.ljmu.ac.uk/id/eprint/12918

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