J Appl Biomed 16:29-33, 2018 | DOI: 10.1016/j.jab.2017.10.009

Proliferation of Toxoplasma gondii (RH strain) is inhibited by the combination of pravastatin and simvastatin with low concentrations of conventional drugs used in toxoplasmosis

Raquel Arruda Sanfelice^a, Larissa Rodrigues Bosqui^a, Suelen Santos da Silva^a, Milena Menegazzo Miranda-Sapla^a, Luciano Aparecido Panagio^b, Italmar Teodorico Navarro^c, Ivete Conchon-Costa^a, Wander Rogério Pavanelli^a, Ricardo Sergio Almeida^b, Idessania Nazareth Costa^a,*

^a Universidade Estadual de Londrina, Departamento de Ciências Patológicas, Laboratório de Parasitologia, Londrina, PR, Brazil

^b Universidade Estadual de Londrina, Departamento de Microbiologia, Laboratório de Micologia Médica e Microbiologia Bucal, Londrina, PR, Brazil

^c Universidade Estadual de Londrina, Departamento de Medicina Veterinária Preventiva, Laboratório de Zoonose e Saúde Pública, Londrina, PR, Brazil

Toxoplasma gondii, an etiologic agent of toxoplasmosis, is an obligate intracellular parasite, which 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. In the light of this information, we determined the effect of pravastatin and simvastatin associated with the current drugs (pyrimethamine and sulfadiazine) as a possible alternative treatment for this infection. Cytotoxicity was evaluated in HeLa cells by MTT assay, which was observed the drug combinations did not affect cell viability. HeLa cells (10⁵) were infected with T. gondii tachyzoites of RH strain (5 × 10⁵) and treated with pravastatin and/or simvastatin combined with pyrimethamine and/or sulfadiazine for 24 h. Our data showed a significant reduction in cell adhesion, infection and mainly parasite proliferation in all treatments. Based on these results, the combination of statins with drugs used in current therapy showed to be a promising therapeutic alternative for toxoplasmosis treatment.

Keywords: Toxoplasma gondii; Hydroxymethylglutaryl-CoA-HMG-CoA reductase; Isoprenoid; Statin; HeLa cell

Received: January 26, 2017; Revised: August 10, 2017; Accepted: October 25, 2017; Published: February 1, 2018  Show citation