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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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Inhibitory action of phenothiazinium dyes against Neospora caninum.pdf - Published Version Available under License Creative Commons Attribution. Download (2MB) | Preview |
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 |
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| 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: | 04 Sep 2021 07:19 |
| DOI or ID number: | 10.1038/s41598-020-64454-x |
| URI: | https://researchonline.ljmu.ac.uk/id/eprint/12918 |
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