Investigação de produtos naturais potenciais na modulação da infecção por Trypanosoma cruzi em modelos de interface materno-fetal humana

Abstract

Congenital Chagas disease is a neglected public health issue with limited treatment options. This study evaluated the potential of oleoresins (ORs) from Copaifera spp. and the extract and isolated compounds from Brazilian red propolis (BRP) against Trypanosoma cruzi infection in trophoblastic cells (BeWo lineage) and human villous placental explants (HVPE). Toxicity was assessed through histological and MTT assays, while the anti-T. cruzi potential was evaluated by proliferation, invasion, egress, and reversibility assays. The ultrastructure of treated trypomastigotes and amastigotes was examined by scanning and transmission electron microscopy. Production of reactive oxygen species (ROS) and lipid bodies were quantified in BeWo cells, and cytokines were measured in both BeWo cells and HVPE. ORs and BRP significantly reduced T. cruzi proliferation in BeWo cells and the parasitic load in HVPE. ORs induced ultrastructural changes in the parasite, including body torsion, flagellar rupture, and cytoplasmic disorganization, whereas BRP did not cause such changes. Both exhibited antioxidant activity, reducing ROS in infected BeWo cells, and BRP modulated lipid metabolism by decreasing lipid bodies. T. cruzi infection altered the cytokine profile in BeWo cells and HVPE; ORs upregulated suppressed cytokines in BeWo cells and downregulated elevated cytokines in HVPE. In conclusion, ORs from Copaifera spp. and BRP, at noncytotoxic concentrations, demonstrated promising potential as candidates for new therapies against congenital Chagas disease, with antiparasitic, antioxidant, and immunomodulatory effects.