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Pravastatin and Simvastatin Pretreatment in Combination with Pyrimethamine and Sulfadiazine Reduces Infection Process of Toxoplasma gondii Tachyzoites (RH Strain) in HeLa Cells

  • Raquel Arruda da Silva SanfeliceEmail author
  • Suelen Santos da Silva
  • Larissa Rodrigues Bosqui
  • Lais Fernanda Machado
  • Milena Menegazzo Miranda-Sapla
  • Luciano Aparecido Panagio
  • Italmar Teodorico Navarro
  • Ivete Conchon-Costa
  • Wander Rogério Pavanelli
  • Ricardo Sergio Almeida
  • Idessania Nazareth CostaEmail author
Original Paper
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Abstract

Purpose

Toxoplasma gondii is a protozoan from phylum Apicomplexa, which causes the toxoplasmosis infection; this one exhibits an apicoplast organelle which assists in the metabolism of isoprenoids and other pivotal mediators for the parasite survival. Statins are drugs that inhibit cholesterol synthesis, blocking the conversion of the substrate HMG-CoA to mevalonate, thus preventing the initial processes of the biosynthesis of these precursors, both in humans and parasite. Our goal was to verify whether the Toxoplasma gondii (RH strain) tachyzoites form pretreated with pravastatin and simvastatin in association with pyrimethamine and sulfadiazine at low concentrations could affect the infection processes, suggesting direct action on protozoa intracellular proliferation through the inhibition of isoprenoids in the parasite’s apicoplast.

Methods

To have the adhesion, infection, and parasite proliferation during experimental infection investigated, HeLa cells (105) were subjected to a 24-hour infection by T. gondii tachyzoites forms of RH strain (5 × 105) pretreated for 30 min with pravastatin and/or simvastatin combined or not with pyrimethamine and sulfadiazine.

Results

Combined with conventional drugs at low concentrations pravastatin and simvastatin inhibit the adhesion, invasion, and intracellular proliferation of T. gondii in HeLa cells which are similar to the positive control.

Conclusion

Pravastatin and simvastatin in association with pyrimethamine and sulfadiazine at low concentrations can be regarded as a promising, effective alternative to toxoplasmosis treatment with reduced side effects.

Keywords

Statin Toxoplasmosis treatment Toxoplasmosis alternative treatment 

Notes

Funding

This work was supported by grants from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).

Compliance with ethical standards

Conflict of interest

The Author(s) declare(s) that the absence of conflicts of interest to disclose.

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Copyright information

© Witold Stefański Institute of Parasitology, Polish Academy of Sciences 2019

Authors and Affiliations

  • Raquel Arruda da Silva Sanfelice
    • 1
    Email author
  • Suelen Santos da Silva
    • 1
  • Larissa Rodrigues Bosqui
    • 1
  • Lais Fernanda Machado
    • 1
  • Milena Menegazzo Miranda-Sapla
    • 1
  • Luciano Aparecido Panagio
    • 2
  • Italmar Teodorico Navarro
    • 3
  • Ivete Conchon-Costa
    • 1
  • Wander Rogério Pavanelli
    • 1
  • Ricardo Sergio Almeida
    • 2
  • Idessania Nazareth Costa
    • 1
    Email author
  1. 1.Laboratório de Parasitologia Experimental, Departamento de Ciências PatológicasUniversidade Estadual de LondrinaLondrinaBrazil
  2. 2.Laboratório de Micologia Médica e Microbiologia Bucal, Departamento de MicrobiologiaUniversidade Estadual de LondrinaLondrinaBrazil
  3. 3.Laboratório de Zoonoses e Saúde Pública, Departamento de Medicina Veterinária PreventivaUniversidade Estadual de LondrinaLondrinaBrazil

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