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

• Published in: Acta parasitologica 2019-09, Vol.64 (3), p.612-616
• Main Authors: Sanfelice, Raquel Arruda da Silva, da Silva, Suelen Santos, Bosqui, Larissa Rodrigues, Machado, Lais Fernanda, Miranda-Sapla, Milena Menegazzo, Panagio, Luciano Aparecido, Navarro, Italmar Teodorico, Conchon-Costa, Ivete, Pavanelli, Wander Rogério, Almeida, Ricardo Sergio, Costa, Idessania Nazareth
• Format: Article
• Language: English
• Subjects: Adhesion; Animal Systematics/Taxonomy/Biogeography; Antibiotics; Antiprotozoal Agents - pharmacology; Biomedical and Life Sciences; Biomedicine; Biosynthesis; Cell proliferation; Cell Survival - drug effects; Cholesterol; Drug Synergism; Drugs; Ecology; Experimental infection; HeLa Cells; Humans; Infections; Intracellular; Life Cycle Stages - drug effects; Low concentrations; Medical Microbiology; Mevalonic acid; Microbiology; Original Paper; Parasites; Parasitology; Pravastatin; Pravastatin - pharmacology; Pretreatment; Protozoa; Pyrimethamine; Pyrimethamine - pharmacology; Side effects; Simvastatin; Simvastatin - pharmacology; Statins; Substrates; Sulfadiazine; Sulfadiazine - pharmacology; Tachyzoites; Terpenes; Toxoplasma - drug effects; Toxoplasma - growth & development; Toxoplasma - physiology; Toxoplasma gondii; Toxoplasmosis; Toxoplasmosis - drug therapy; Toxoplasmosis - parasitology
• ISSN: 1230-2821; 1896-1851
• DOI: 10.2478/s11686-019-00076-2

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 (10 5 ) were subjected to a 24-hour infection by T. gondii tachyzoites forms of RH strain (5 × 10 5 ) 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.