Abstract

The combination of pyrimethamine and sulfadiazine is the standard care in cases of congenital toxoplasmosis. However, therapy with these drugs is associated with severe and sometimes life-threatening side effects. The investigation of phytotherapeutic alternatives to treat parasitic diseases without acute toxicity is essential for the advancement of current therapeutic practices. The present study investigates the antiparasitic effects of oleoresins from different species of Copaifera genus against T. gondii. Oleoresins from C. reticulata, C. duckei, C. paupera, and C. pubiflora were used to treat human trophoblastic cells (BeWo cells) and human villous explants infected with T. gondii. Our results demonstrated that oleoresins were able to reduce T. gondii intracellular proliferation, adhesion, and invasion. We observed an irreversible concentration-dependent antiparasitic action in infected BeWo cells, as well as parasite cell cycle arrest in the S/M phase. The oleoresins altered the host cell environment by modulation of ROS, IL-6, and MIF production in BeWo cells. Also, Copaifera oleoresins reduced parasite replication and TNF-α release in villous explants. Anti-T. gondii effects triggered by the oleoresins are associated with immunomodulation of the host cells, as well as, direct action on parasites.

Highlights

  • The combination of pyrimethamine and sulfadiazine is the standard care in cases of congenital toxoplasmosis

  • We observed that the treatment with all four oleoresins in the concentration of 128 μg/mL significantly reduced the percentage of intracellular parasites, as follow: C. reticulata (~ 30%; *P = 0.0339), C. duckei (~ 60%; ****P < 0.0001), C. paupera (~ 30%; *P = 0.0404) and C. pubiflora (~ 65%; ****P < 0.0001) compared to untreated villous explants

  • In the context of congenital transmission, when a woman gets the infection during pregnancy, recommended drugs for treatment are limited to a combination of sulfadiazine plus pyrimethamine (SDZ + PYR) and ­spiramycin[8,19,20,24]

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Summary

Introduction

The combination of pyrimethamine and sulfadiazine is the standard care in cases of congenital toxoplasmosis. Addressing the impact of oleoresins in the intracellular proliferation of T. gondii (24 h), the concentrations 64 and 32 μg/mL of oleoresins reduced the replication of pre-treated parasites compared to untreated parasites, as follows: C. reticulata, C. duckei, C. pubiflora (****P < 0.0001) and C. paupera (64 and 32 μg/mL; ****P < 0.0001 and ***P = 0.0002, respectively) (Fig. 4B).

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