Synergic in vitro combinations of artemisinin, pyrimethamine and methylene blue against Neospora caninum

Vet Parasitol. 2018 Jan 15:249:92-97. doi: 10.1016/j.vetpar.2017.11.014. Epub 2017 Dec 2.

Abstract

Neospora caninum is a member of Apicomplexa phylum, the causative agent of neosporosis. The neosporosis combat is not well established and several strategies related to vaccine, chemotherapy and immune modulation are under development. In this work, we evaluated the effects of artemisinin (Art), methylene blue (MB) and pyrimethamine (Pyr) alone or associated, on N. caninum proliferation and elimination using LacZ tagged tachyzoites. The reactive oxygen species (ROS) production after incubation with Art were also performed. Our results indicate that combinations of classical antimalarial drugs improve the parasite control, allowing the use of three drugs in a single dose. Additionally, artemisinin demonstrated distinct ROS production patterns in intra and extracellular N. caninum forms. The drug repurposing appears as a suitable approach, allowing a fast and safe method to evaluate old drugs but novel candidates against neosporosis.

Keywords: Artemisinin; Methylene blue; Neospora caninum; Pyrimethamine.

MeSH terms

  • Animals
  • Antimalarials / pharmacology*
  • Antimalarials / therapeutic use
  • Artemisinins / pharmacology
  • Artemisinins / therapeutic use
  • Chlorocebus aethiops
  • Coccidiosis / drug therapy
  • Drug Synergism
  • Drug Therapy, Combination / veterinary
  • In Vitro Techniques
  • Methylene Blue / pharmacology
  • Methylene Blue / therapeutic use
  • Neospora / drug effects*
  • Pyrimethamine / pharmacology
  • Pyrimethamine / therapeutic use
  • Vero Cells

Substances

  • Antimalarials
  • Artemisinins
  • Methylene Blue
  • Pyrimethamine