Browsing by Author "Pereira, Wagner Luiz"

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    Association of electroanalytical and spectrophotometric methods to evaluate the antioxidant activity of isobenzofuranone in primary cultures of hippocampal neurons.
    (2020) Teixeira, Aniely dos Reis; Teixeira, Róbson Ricardo; Ribeiro, Iara Mariana Léllis; Pereira, Wagner Luiz; Manhabosco, Taíse Matte; Brito, Ana Carolina Ferreira de; Oliveira, Laser Antônio Machado de; Nogueira, Katiane de Oliveira Pinto Coelho
    The isobenzofuran-1(3H)-ones (phthalides) exhibit various biological activities, including antioxidant activity on reactive oxygen species (ROS). An excess of ROS that cannot be naturally contained by cellular enzymatic systems is called redox imbalance, which damage cell membranes, proteins, and DNA, thereby possibly triggering neuronal death in several neurodegenerative diseases. Considering our ongoing efforts to find useful compounds to control redox imbalance, herein we evaluated the antioxidant activity of two phtalides (compounds 3 and 4), using primary cultures of hippocampal neurons. Spectrophotometric assays showed that compound 3 significantly reduced (p ≤ 0.05) ROS levels and lipid peroxidation compared to the control treatment, while compound 4 was unable at any of the tested concentrations. Despite their structural similarity, these compounds behave differently in the intracellular environment, which was reliably corroborated by the determination of oxidation potentials via cyclic voltammetry. It was demonstrated that compound 3 presents a lower oxidation potential. The combination of the mentioned methods allowed us to find a strong correlation between the chemical structure of compounds and their biological effects. Taking together, the results indicate that compound 3 presents desirable characteristics to act as a candidate pharmacological agent for use in the prevention and treatment of neurodegenerative diseases.
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    In vitro tripanocidal effect of 1,8-dioxooctahydroxanthenes (xanthenodiones) and tetraketones and improvement of cardiac parameters in vivo.
    (2020) Menezes, Ana Paula de Jesus; Silva, Milene Lopes da; Pereira, Wagner Luiz; Costa, Guilherme de Paula; Horta, Aline Luciano; Mendonça, Andréa Aparecida dos Santos; Carneiro, Ana Cláudia Alvarenga; Souza, Débora Maria Soares de; Novaes, Rômulo Dias; Teixeira, Róbson Ricardo; Silva, André Talvani Pedrosa da
    Objective: Trypanosoma cruzi infection affects millions of people worldwide, and the drugs available for its treatment have limited efficacy. 1,8-Dioxooctahydroxanthenes and tetraketones are compounds with important biological applications. The aim of this study was to assess the trypanocidal and inflammatory activities of nine 1,8-dioxooctahydroxanthenes (1–9) and three tetraketones (10–12). Methods and results: By in vitro killing assay, three compounds were able to eliminate CL TdTomato expressing strain of T. cruzi, 9 (IC50 = 30.65mM), 10 (IC50 = 14.11mM), and 11 (IC50 = 26.43mM). However, only 9 was not toxic to Vero cells. Next, to evaluate the in vivo antitrypanosomal and immunological efficacy of 9, Swiss mice were infected with the Y and CL strains of T. cruzi and treated for 10 days with 50 mg/kg of 9. This compound reduced the cardiac inflammatory infiltration in animals infected with both strains. Rank's ligand (RankL), CCL2, and interferon (IFN)-g were measured in the cardiac tissue homogenate of the Y-strain-infected animals, and no interference of 9 was observed. However, compound 9 increased the RankL and interleukin (IL)-10 levels in CL-infected mice. No hepatic and renal toxicity was observed. Conclusion: Our findings showed that 1,8-dioxooctahydroxanthene has antiparasitic effect and ameliorates the cardiac inflammatory parameters related to T. cruzi infection.
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    Neuroprotective effect of isobenzofuranones on hydrogen peroxide-mediated redox imbalance in primary cultures of hippocampal neurons.
    (2020) Ribeiro, Iara Mariana Léllis; Pereira, Wagner Luiz; Nogueira, Leonardo Brandão; Oliveira, Laser Antônio Machado de; Teixeira, Róbson Ricardo; Nogueira, Katiane de Oliveira Pinto Coelho
    In live organisms, there is a balance between the production of reactive oxygen species (ROS) and their neutralization. The increased level of these species leads to a condition called redox imbalance. The aim of this study was to evaluate the protective action of isobenzofuranones in primary cultures of hippocampal neurons subjected to redox imbalance. To accomplish this, MTT and LIVE/DEAD assays were initially performed. In the cultures pretreated with isobenzofuranones 1 and 2, there was a higher number of live cells when compared to that in the untreated ones. Regarding redox imbalance, there was a significant increase in the intracellular levels of ROS. The cultures pretreated with isobenzofuranones showed a reduction in ROS levels. Lipid peroxidation caused by oxidative damage was significantly reduced in the cultures pretreated with isobenzofuranones 1 and 2. Taken together, these data show the ability of isobenzofuranones 1 and 2 to significantly minimize cytotoxicity, cell death, intracellular levels of ROS and lipid peroxidation induced by redox imbalance. These results suggest that isobenzofuranones 1 and 2 represent a possible alternative therapy for the neurodegenerative disturbances that are triggered by ROS production increases.