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Acta tropica v.167, 2017년, pp.208 - 215   SCI SCIE
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

Pravastatin and simvastatin inhibit the adhesion, replication and proliferation of Toxoplasma gondii (RH strain) in HeLa cells

Sanfelice, Raquel Arruda (Departamento de Patologia Experimental – ) ; da Silva, Suelen Santos (Laboratório de Protozoologia Experimental, Universidade Estadual de Londrina, Londrina, PR, Brazil ) ; Bosqui, Larissa Rodrigues (Departamento de Patologia Experimental – ) ; Miranda-Sapla, Milena Menegazzo (Laboratório de Protozoologia Experimental, Universidade Estadual de Londrina, Londrina, PR, Brazil ) ; Barbosa, Bellisa Freitas (Departamento de Patologia Experimental – ) ; Silva, Rafaela José (Laboratório de Protozoologia Experimental, Universidade Estadual de Londrina, Londrina, PR, Brazil ) ; Ferro, Eloísa A. Vieira (Departamento de Patologia Experimental – ) ; Panagio, Luciano Aparecido (Laboratório de Protozoologia Experimental, Universidade Estadual de Londrina, Londrina, PR, Brazil ) ; Navarro, Italmar Teodorico (Laboratório de Histologia e Embriologia, Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil ) ; Bordignon, Juliano (Laboratório de Histologia e Embriologia, Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil ) ; Conchon-Costa, Ivete (Laboratório de Histologia e Embri ) ; Pavanelli, Wander Rogerio ; Almeida, Ricardo Sergio ; Costa, Idessania Nazareth ;
  • 초록  

    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 (1×10 5 ) were infected with T. gondii tachyzoites (5×10 5 ) 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 (5×10 5 ) 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. Highlights Simvastatin and pravastatin evaluated in cells infected with Toxoplasma gondii . Analyzed adhesion, cell infection and proliferation of T. gondii in HeLa cells. Reduction in adhesion, and proliferation of the infection in the treated cells. Simvastatin and pravastatin are alternative targets for the treatment of toxoplasmosis. Graphical abstract [DISPLAY OMISSION]


  • 주제어

    Toxoplasma gondii .   HeLa cell .   Statins.  

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