A Quercetina reduz a infecção por Toxoplasma gondii nos modelos placentários in vitro e ex vivo

Abstract

Toxoplasmosis is a disease caused by the obligate intracellular protozoan Toxoplasma gondii, which is capable of infecting all nucleated cells of birds and mammals and is therefore considered one of the most successful parasites in terms of infection. One of the routes of toxoplasmosis transmission is congenital transmission, which most often occurs when the mother acquires the infection for the first time during pregnancy. The ability of the parasite to cross the placental barrier and infect the embryo can lead to fetal malformations, spontaneous abortion, and prematurity, among other manifestations. Currently, the traditional treatment recommended by the Brazilian Ministry of Health consists of spiramycin until the 16th week of pregnancy, followed by the combination of pyrimethamine, sulfadiazine, and folinic acid after the 16th week. However, these treatments have limitations, including teratogenic potential and the possibility of parasite resistance development. Quercetin, for instance, is a natural compound belonging to the flavonol class and is found in fruits and vegetables. It has attracted considerable interest due to its diverse pharmacological properties, particularly its antioxidant activity. In this context, we investigated the use of quercetin as a potential treatment for congenital toxoplasmosis using in vitro, ex vivo, and in silico approaches. We demonstrated that quercetin was able to inhibit intracellular parasite proliferation while preserving cell viability in both in vitro and ex vivo models. In the in vitro model, quercetin impaired parasite adhesion and invasion of host cells, reduced lipid droplet production in T. gondii-infected cells, and preserved antioxidant capacity. In addition, quercetin modulated cytokine production, contributing to the regulation of the immune response and preventing its exacerbation through the modulation of IL-4 and IL-8 expression. Finally, in silico analysis demonstrated affinity for the parasite target TgHGPRT and revealed drug-like characteristics based on the pharmacological properties evaluated. Therefore, quercetin exhibited a potential role in controlling T. gondii parasitism while maintaining a cytoprotective profile, which is essential at the maternal–fetal interface.