Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Science, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil.
Department of Parasitology, Institute of Biomedical Sciences, Universidade Federal de Uberlândia, Uberlândia, MG, Brazil.
Biomed Pharmacother. 2024 Oct;179:117425. doi: 10.1016/j.biopha.2024.117425. Epub 2024 Sep 11.
Congenital Chagas disease (CCD) is a worldwide neglected problem with significant treatment limitations. This study aimed to evaluate the potential of Copaifera spp. oleoresins (ORs) against Trypanosoma cruzi infection in trophoblast cells (BeWo lineage) and human chorionic villous explants (HCVE). The cytotoxicity of ORs was investigated using LDH and MTT assays. T. cruzi (Y strain) proliferation, invasion and reversibility were assessed in OR-treated BeWo cells, and proliferation was evaluated in OR-treated HCVE. The ultrastructure of T. cruzi trypomastigotes and amastigotes treated with ORs were analyzed by scanning and transmission electronic microscopy. ROS production in infected and treated BeWo cells and cytokines in BeWo and HCVE were measured. The ORs irreversibly decreased T. cruzi invasion, proliferation and release in BeWo cells by up to 70 %, 82 % and 80 %, respectively, and reduced parasite load in HCVE by up to 80 %. Significant structural changes in treated parasites were observed. ORs showed antioxidant capacity in BeWo cells, reducing ROS production induced by T. cruzi infection. Also, T. cruzi infection modulated the cytokine profile in both BeWo cells and HCVE; however, treatment with ORs upregulated cytokines decreased by T. cruzi infection in BeWo cells, while downregulated cytokines increased by the T. cruzi infection in HCVE. In conclusion, non-cytotoxic concentrations of Copaifera ORs demonstrated promising potential for controlling T. cruzi infection in models of the human maternal-fetal interface.
先天性恰加斯病（CCD）是一个全球性的被忽视的问题，治疗方法存在很大的局限性。本研究旨在评估 Copaifera spp. 油树脂（ORs）在滋养层细胞（BeWo 系）和人绒毛膜绒毛外植体（HCVE）中对抗 Trypanosoma cruzi 感染的潜力。通过 LDH 和 MTT 测定法研究了 ORs 的细胞毒性。在 OR 处理的 BeWo 细胞中评估了 T. cruzi（Y 株）的增殖、侵袭和逆转，在 OR 处理的 HCVE 中评估了增殖。用扫描和透射电子显微镜分析了 OR 处理的 T. cruzi 锥虫体和无鞭毛体的超微结构。测量了感染和处理的 BeWo 细胞中的 ROS 产生以及 BeWo 和 HCVE 中的细胞因子。ORs 不可逆地降低了 BeWo 细胞中的 T. cruzi 侵袭、增殖和释放，分别降低了 70%、82%和 80%，并降低了 HCVE 中的寄生虫负荷 80%。观察到处理后的寄生虫有明显的结构变化。ORs 在 BeWo 细胞中表现出抗氧化能力，降低了 T. cruzi 感染引起的 ROS 产生。此外，T. cruzi 感染调节了 BeWo 细胞和 HCVE 中的细胞因子谱；然而，OR 处理上调了由 T. cruzi 感染下调的细胞因子，而下调了由 T. cruzi 感染上调的细胞因子。总之，非细胞毒性浓度的 Copaifera ORs 显示出在人母胎界面模型中控制 T. cruzi 感染的有希望的潜力。
