Pravastatin and Simvastatin Pretreatment in Combination with Pyrimethamine and Sulfadiazine Reduces Infection Process of Toxoplasma gondii Tachyzoites (RH Strain) in HeLa Cells
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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.
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.
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.
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.
KeywordsStatin Toxoplasmosis treatment Toxoplasmosis alternative treatment
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.
- 3.Christians U, Jacobsen W, Floren LC (1998) Metabolism and drug interactions of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in transplant patients: are the statins mechanistically similar? Pharmacol Ther 80:1–34. https://doi.org/10.1016/S0163-7258(98)00016-3 CrossRefPubMedGoogle Scholar
- 13.Nyilasi I, Kocsubé S, Krizsán K, Galgóczy L, Pesti M, Papp T et al (2010) In vitro synergistic interactions of the effects of various statins and azoles against some clinically important fungi. FEMS Microbiol Lett 307:175–184. https://doi.org/10.1111/j.1574-6968.2010.01972.x CrossRefPubMedGoogle Scholar
- 15.Sanfelice AR, Machado LF, Bosqui LR, Miranda-Sapla MM, Tomiotto-Pellissier F, de Alcântara Dalevedo G et al (2017) Activity of rosuvastatin in tachyzoites of Toxoplasma gondii (RH strain) in HeLa cells. Exp Parasitol 181:75–81. https://doi.org/10.1016/j.exppara.2017.07.009 CrossRefPubMedGoogle Scholar
- 16.Sanfelice RA, da Silva SS, Bosqui LR, Miranda-Sapla MM, Barbosa BF, Silva RJ et al (2017) Pravastatin and simvastatin inhibit the adhesion, replication and proliferation of Toxoplasma gondii (RH strain) in HeLa cells. Acta Trop 167:208–215. https://doi.org/10.1016/j.actatropica.2016.12.006 CrossRefPubMedGoogle Scholar
- 17.Sanfelice RA, Bosqui LR, da Silva SS, Miranda-Sapla MM, Panagio LA, Navarro IT et al (2018) Proliferation of Toxoplasma gondii (RH strain) is inhibited by the combination of pravastatin and simvastatin with low concentrations of conventional drugs used in toxoplasmosis. J Appl Biomed 16:29–33. https://doi.org/10.1016/J.JAB.2017.10.009 CrossRefGoogle Scholar
- 18.Schaefer EJ, McNamara JR, Tayler T, Daly JA, Gleason JL, Seman LJ et al (2004) Comparisons of effects of statins (atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin) on fasting and postprandial lipoproteins in patients with coronary heart disease versus control subjects. Am J Cardiol 93:31–39. https://doi.org/10.1016/j.amjcard.2003.09.008 CrossRefPubMedGoogle Scholar