Study of combinations of Menadione with vitamin C with Menadione with Praziquantel in adult worms of Schistosoma mansoni in vitro

• Grant number: 17/04885-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2017
• End date: December 31, 2017
• Field of knowledge: Biological Sciences - Parasitology - Helminthology of Parasites
• Principal Investigator: Lizandra Guidi Magalhães
• Grantee: Ana Carolina Gonçalves
• Host Institution: Pró-Reitoria Adjunta de Pesquisa e Pós-Graduação. Universidade de Franca (UNIFRAN). Franca , SP, Brazil

Abstract

Schistosomiasis is a parasitic disease caused by the helminth Schistosoma mansoni and it is estimated about one and a half million people live in areas of possible contagion in Brazil. The most commonly used treatment against this disease is Praziquantel (PZQ), which is an effective drug against the parasite, but does not prevent reinfection, and reports have shown the growing appearance of less drug-sensitive strains. In view of the need to develop new treatment strategies for the treatment of schistosomiasis, the combination study is a relevant strategy, as it may lead to better biological activity with less toxicity, thus providing better selectivity and greater efficacy of the combined substances when compared to the administration of the substances separately. Menadione (MEN), also known as Vitamin K3, is a quinone-derived naphthoquinone, which has reported several biological activities, including schistosomicidal activity in vitro and in vivo. Studies also demonstrate that the combination of MEN and Vitamin C (VC) has a synergistic effect against several tumor cells and the parasite Trypanosoma cruzi. In view of these facts, the present project aims to study the effect of the combination of MEN and VC and MEN and PZQ in adult worms of Schistosoma mansoni in vitro. Initially, the viability of the adult worms incubated with MEN, VC and PZQ will be reevaluated and the Lethal Concentration of 50% (LC50) in vitro. Then the synergistic, additive or antagonistic effects of the MEN-VC and MEN-PZQ combinations will be determined, as well as the effective concentrations of each combination. The morphology of adult worms will be evaluated by transmission electron microscopy (TEM) after incubation with the combinations or with the separated substances. Finally, the cytotoxicity of the combinations and the separated substances will be evaluated in vitro. (AU)