title: Pravastatin and simvastatin inhibit the adhesion, replication and proliferation of Toxoplasma gondii (RH strain) in HeLa cells.
abstract: The conventional treatment for toxoplasmosis with pyrimethamine and sulfadiazine shows toxic effects to the host, and it is therefore necessary to search for new drugs. Some studies suggest the use of statins, which inhibit cholesterol synthesis in humans and also the initial processes of isoprenoid biosynthesis in the parasite. Thus, the objective of this study was to evaluate the activity of the statins pravastatin and simvastatin in HeLa cells infected in vitro with the RH strain of T. gondii. HeLa cells (1×105) were infected with T. gondii tachyzoites (5×105) following two different treatment protocols. In the first protocol, T. gondii tachyzoites were pretreated with pravastatin (50 and 100μg/mL) and simvastatin (1.56 and 3.125μg/mL) for 30min prior to infection. In the second, HeLa cells were first infected (5×105) with tachyzoites and subsequently treated with pravastatin and simvastatin for 24h at the concentrations noted above. Initially, we evaluated the cytotoxicity of drugs by the MTT assay, number of tachyzoites adhered to cells, number of infected cells, and viability of tachyzoites by trypan blue exclusion. The supernatant of the cell cultures was collected post-treatment for determination of the pattern of Th1/Th2/Th17 cytokines by cytometric bead array. There was no cytotoxicity to HeLa cells with 50 and 100μg/mL pravastatin and 1.56 and 3.125μg/mL simvastatin. There was no change in the viability of tachyzoites that received pretreatment. Regarding the pre- and post-treatment of the cells with pravastatin and simvastatin alone, there was a reduction in adhesion, invasion and proliferation of cells to T. gondii. As for the production of cytokines, we found that IL-6 and IL-17 were significantly reduced in cells infected with T. gondii and treated with pravastatin and simvastatin, when compared to control. Based on these results, we can infer that pravastatin and simvastatin alone possess antiproliferative effects on tachyzoites forms of T. gondii, giving these drugs new therapeutic uses.
authors.affiliation: Departamento de Patologia Experimental - Laboratório de Protozoologia Experimental, Universidade Estadual de Londrina, Londrina, PR, Brazil.
authors.forename: Raquel Arruda
authors.initials: RA
authors.lastname: Sanfelice
authors.affiliation: Departamento de Patologia Experimental - Laboratório de Protozoologia Experimental, Universidade Estadual de Londrina, Londrina, PR, Brazil.
authors.forename: Suelen Santos
authors.initials: SS
authors.lastname: da Silva
authors.affiliation: Departamento de Patologia Experimental - Laboratório de Protozoologia Experimental, Universidade Estadual de Londrina, Londrina, PR, Brazil.
authors.forename: Larissa Rodrigues
authors.initials: LR
authors.lastname: Bosqui
authors.affiliation: Departamento de Patologia Experimental - Laboratório de Protozoologia Experimental, Universidade Estadual de Londrina, Londrina, PR, Brazil.
authors.forename: Milena Menegazzo
authors.initials: MM
authors.lastname: Miranda-Sapla
authors.affiliation: Laboratório de Histologia e Embriologia, Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil.
authors.forename: Bellisa Freitas
authors.initials: BF
authors.lastname: Barbosa
authors.affiliation: Laboratório de Histologia e Embriologia, Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil.
authors.forename: Rafaela José
authors.initials: RJ
authors.lastname: Silva
authors.affiliation: Laboratório de Histologia e Embriologia, Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil.
authors.forename: Eloísa A Vieira
authors.initials: EAV
authors.lastname: Ferro
authors.affiliation: Departamento de Microbiologia - Laboratório de Micologia Médica e Microbiologia Bucal, Universidade Estadual de Londrina, PR, Londrina, Brazil.
authors.forename: Luciano Aparecido
authors.initials: LA
authors.lastname: Panagio
authors.affiliation: Departamento de Medicina Veterinária Preventiva - Laboratório de Zoonoses e Saúde Pública, Universidade Estadual de Londrina, Londrina, PR, Brazil.
authors.forename: Italmar Teodorico
authors.initials: IT
authors.lastname: Navarro
authors.affiliation: Laboratório de Virologia Molecular, Instituto Carlos Chagas, ICC/Fiocruz, Curitiba, PR, Brazil.
authors.forename: Juliano
authors.initials: J
authors.lastname: Bordignon
authors.affiliation: Departamento de Patologia Experimental - Laboratório de Protozoologia Experimental, Universidade Estadual de Londrina, Londrina, PR, Brazil.
authors.forename: Ivete
authors.initials: I
authors.lastname: Conchon-Costa
authors.affiliation: Departamento de Patologia Experimental - Laboratório de Protozoologia Experimental, Universidade Estadual de Londrina, Londrina, PR, Brazil.
authors.forename: Wander Rogerio
authors.initials: WR
authors.lastname: Pavanelli
authors.affiliation: Departamento de Microbiologia - Laboratório de Micologia Médica e Microbiologia Bucal, Universidade Estadual de Londrina, PR, Londrina, Brazil.
authors.forename: Ricardo Sergio
authors.initials: RS
authors.lastname: Almeida
authors.affiliation: Departamento de Patologia Experimental - Laboratório de Protozoologia Experimental, Universidade Estadual de Londrina, Londrina, PR, Brazil. Electronic address: idessania@hotmail.com.
authors.forename: Idessania Nazareth
authors.initials: IN
authors.lastname: Costa
mesh_terms: D002448:Cell Adhesion; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D017035:Pravastatin / Q000494:pharmacology*; D019821:Simvastatin / Q000494:pharmacology*; D014122:Toxoplasma / Q000187:drug effects*
chemical_list: D019821:Simvastatin; D017035:Pravastatin
keywords: HeLa cell; Statins; Toxoplasma gondii