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Navegando IF - Trabalhos de Conclusão de Curso por Autor "Alonso, Antonio"
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Item Estudo do mecanismo de ação da atividade leishmanicida da miltefosina(Universidade Federal de Goiás, 2023-08-17) Fontenele, Thaís Moreira; Alonso, Antonio; Alonso, Antonio; Mendanha Neto, Sebastião Antônio; Marquezin, Cássia AlessandraMiltefosine (MT) is an internationally approved oral drug for the treatment of leishmaniasis, however, its mechanisms of action are not clear yet. In this study, we used electron paramagnetic resonance (EPR) spectroscopy associated with the spin label method to demonstrate that MT causes membrane rigidity in promastigotes of L. amazonensis after treatments of 24, 48 and 72 h. The EPR spectra were consistent with the occurrence of intense lipoperoxidation and oxidation of membrane proteins. These results agree with reported works showing that MT also causes changes in the mitochondrial membrane potential, as well as several compounds that also cause membrane rigidity in the Leishmania parasite. As previous studies have shown that MT causes great fluidity in the parasite's membrane after two hours of treatment, the results of this work suggest that the primary action of MT is on the plasmatic membrane, with probable alteration in the ionic balance, like ivermectin that alters the electrical potential on the parasite membrane and causes membrane rigidity as has been reported.Item Mecanismos de ação das atividades leishmanicidas da anfotericina B e miltefosina(Universidade Federal de Goiás, 2024-02-07) Silva, David de Ribamar Antunes da; Alonso, Antonio; Alonso, Antonio; Vieira, Sílvio Leão; Itikawa, Emerson NobuyukiLeishmaniasis is a disease caused by parasites of the genus Leishmania, and its treatment involves the use of medications, with meglumine antimoniate, amphotericin B (AmB), and miltefosine (MTF) being the preferred choices according to health department guidelines. Electron paramagnetic resonance (RPE) spectroscopy with spin labels was employed to demonstrate that the drugs MTF and AmB induce rigidity in the membrane of the L. amazonensis parasite. Membrane rigidity was associated with lipid peroxidation and/or oxidation of membrane proteins, resulting from an increase in the formation of reactive oxygen species (ROS) promoted by the medications. Similar tests were conducted on J774A.1 macrophages, but membrane rigidity was not observed, suggesting that their production of nitric oxide (NO) may reduce oxidative stress. For MTF, membrane rigidity in Leishmania is not the result of its direct interactions with the membrane because immediately after treatment, MTF induces fluidity. For measurements immediately after treatment, where the incubation period is insufficient for oxidative stress to occur, AmB also induces membrane rigidity, but this effect was observed at a drug concentration 100 times higher. This result indicates that for higher concentrations of AmB, EPR spectroscopy can detect direct interactions of AmB with the parasite membrane, probably forming putative AmB/ergosterol aggregates that cause membrane rigidity. In J774A.1 macrophages, the effects of MTF-induced fluidity and AmB-induced rigidity were also observed. These effects occurred for short incubation periods and at the respective drug concentrations that showed cytotoxicity. Our studies have shown that these drugs act on the membrane and suggest that the mechanisms of action of their antileishmanial activities are associated with their primary effects on the cell membrane. Membrane alteration can cause ionic imbalance, which may affect mitochondrial membrane potential and, thus, increase ROS formation.