Toxoplasma gondii, toxoplasmosis agent, is a obligate intracellular protozoan that is able of infecting a broad spectrum of vertebrate's cells. Toxoplasmosis is a pathology related to severe damages to immunocompromised hosts and its current chemotherapy is quite restricted, being more used the combination of sulfadiazine and pyrimethamine, which is a therapy associated with adverse reactions. This fact highlights the importance of the study of new drugs against Toxoplasma gondii. Has been studied the biological effect of new metallocomplexe compounds, which are inorganic compounds that present promising biological activity as fungicide, bactericide and antiviral. The metallocomplexes, dinuclear ferric compounds N0414 (Fe alfanaftol BMPA) and N5814 (Fe beta-naphthol BMPA) showed activity against Toxoplasma gondii in vitro and it was nontoxic to LLC-MK2 cells, being able to reduce the activity of crucial antioxidant enzymes for the defense of the parasite. In this project, it will be investigated the activities of compounds of the metallocomplexes family as the compounds coordinated to sulfadiazine as the nucleus compound of ferric N0414 and N5814, which showed anti-Toxoplasma gondii activities and were able to eliminate the infection in almost all host cells. In further steps, we will investigate what kind of death the parasite undergoes after the treatment with the compounds through the ultrastructure analysis and the usage of specific markers by fluorescence microscopy. The compounds will also be used in vivo tests with mouse models in the acute phase of toxoplasmosis to prove the efficacy of these compounds.
Toxoplasmosis is a disease caused by intracellular obligate protozoan, Toxoplasma gondii. And it can be obtained mainly through the oral route, through the ingestion of oocysts or tissue cysts. For this reason, the intestinal epithelium is a cellular model that makes it possible to study the first line of defense against this type of infection. After infection, the protozoan invades intestinal cells, changing the physiology and functions of the intestinal epithelial barrier. In view of this, we analyzed the morphological changes and the microenvironment, in vitro, which are modified in the intestinal epithelial cell during the process of infection and evasion of Toxoplasma gondii.
Toxoplasma gondii is a protozoan parasite responsible for toxoplasmosis, and may be causing any problems in different systems. Some of these complications are associated with the change of intercellular communication mediated by Junctions Communicators that allows direct communication between tissues. However, there are still systems that are not fully consistent with the junctional communication, including the innate immune system, represented by Macrophages. Thus, we used J774-G8 macrophage cell line culture infected by the RH strain of Toxoplasma in its tachyzoite form. The results revealed that in J774-G8 cells The Cx43 and Phalloidin proteins interact in the plasma membrane of the J774-G8 lineage, and they undergo a sensitive reduction in the membrane after 72 hours of infection with the parasite Toxoplasma gondii. The evaluation of the Cx43 protein expression by immunoelectrophoretic transfer has been shown to be altered (elevated) in J774-G8 macrophage cells infected with the parasite Toxoplasma gondii 24 and 48 hours compared to uninfected cells.
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