ALESSANDRA CHOQUETA DE TOLEDO ARRUDA
Projetos de Pesquisa
Unidades Organizacionais
LIM/20 - Laboratório de Terapêutica Experimental, Hospital das Clínicas, Faculdade de Medicina
8 resultados
Resultados de Busca
Agora exibindo 1 - 8 de 8
- Structure-Activity Association of Flavonoids in Lung Diseases(2014) LAGO, Joao Henrique G.; TOLEDO-ARRUDA, Alessandra C.; MERNAK, Marcia; BARROSA, Kaidu H.; MARTINS, Milton A.; TIBERIO, Iolanda F. L. C.; PRADO, Carla M.Flavonoids are polyphenolic compounds classified into flavonols, flavones, flavanones, isoflavones, catechins, anthocyanidins, and chalcones according to their chemical structures. They are abundantly found in Nature and over 8,000 flavonoids have from different sources, mainly plant materials, have been described. Recently reports have shown the valuable effects of flavonoids as antiviral, anti-allergic, antiplatelet, antitumor, antioxidant, and anti-inflammatory agents and interest in these compounds has been increasing since they can be helpful to human health. Several mechanisms of action are involved in the biological properties of flavonoids such as free radical scavenging, transition metal ion chelation, activation of survival genes and signaling pathways, regulation of mitochondrial function and modulation of inflammatory responses. The anti-inflammatory effects of flavonoids have been described in a number of studies in the literature, but not frequently associated to respiratory disease. Thus, this review aims to discuss the effects of different flavonoids in the control of lung inflammation in some disorders such as asthma, lung emphysema and acute respiratory distress syndrome and the possible mechanisms of action, as well as establish some structure-activity relationships between this biological potential and chemical profile of these compounds.
conferenceObject Sakuranetin Derived From Baccharis Retusa (asteraceae) Reduces Lung Vascular Inflammation And Remodeling Induced By Chronic Allergic Airway Inflammation(2013) SAKODA, C. P. P.; TOLEDO, A. C.; PINHEIRO, N. M.; PERINI, A.; GRECCO, S.; TIBERIO, I. F. L. C.; HIYANE, M. I.; CAMARA, N. O. S.; MARTINS, M. A.; LAGO, J. H. G.; PRADO, C. M.- Plant Proteinase Inhibitor BbCI Modulates Lung Inflammatory Responses and Mechanic and Remodeling Alterations Induced by Elastase in Mice(2017) ALMEIDA-REIS, Rafael; THEODORO-JUNIOR, Osmar A.; OLIVEIRA, Bruno T. M.; OLIVA, Leandro V.; TOLEDO-ARRUDA, Alessandra C.; BONTURI, Camila R.; BRITO, Marlon V.; LOPES, Fernanda D. T. Q. S.; PRADO, Carla M.; FLORENCIO, Ariana C.; MARTINS, Milton A.; OWEN, Caroline A.; LEICK, Edna A.; OLIVA, Maria L. V.; TIBERIO, Iolanda F. L. C.Background. Proteinases play a key role in emphysema. Bauhinia bauhinioides cruzipain inhibitor (BbCI) is a serine-cysteine proteinase inhibitor. We evaluated BbCI treatment in elastase-induced pulmonary alterations. Methods. C57BL/6 mice received intratracheal elastase (ELA group) or saline (SAL group). One group of mice was treated with BbCI (days 1, 15, and 21 after elastase instillation, ELABC group). Controls received saline and BbCI (SALBC group). After 28 days, we evaluated respiratory mechanics, exhaled nitric oxide, and bronchoalveolar lavage fluid. In lung tissue we measured airspace enlargement, quantified neutrophils, TNF alpha-, MMP-9-, MMP-12-, TIMP-1-, iNOS-, and eNOS-positive cells, 8-iso-PGF2 alpha, collagen,and elastic fibers in alveolar septa and airways. MUC-5-positive cells were quantified only in airways. Results. BbCI reduced elastase-induced changes in pulmonary mechanics, airspace enlargement and elastase-induced increases in total cells, and neutrophils in BALF. BbCI reduced macrophages and neutrophils positive cells in alveolar septa and neutrophils and TNF alpha-positive cells in airways. BbCI attenuated elastic and collagen fibers, MMP-9- and MMP-12-positive cells, and isoprostane and iNOS-positive cells in alveolar septa and airways. BbCI reduced MUC5ac-positive cells in airways. Conclusions. BbCI improved lung mechanics and reduced lung inflammation and airspace enlargement and increased oxidative stress levels induced by elastase. BbCI may have therapeutic potential in chronic obstructive pulmonary disease.
- Sakuranetin reverses vascular peribronchial and lung parenchyma remodeling in a murine model of chronic allergic pulmonary inflammation(2016) SAKODA, Camila Pivari Pedroso; TOLEDO, Alessandra Choqueta de; PERINI, Adenir; PINHEIRO, Nathalia Montouro; HIYANE, Meire Ioshie; GRECCO, Simone dos Santos; TIBERIO, Iolanda de Fatima Lopes Calvo; CAMARA, Niels Olsen Saraiva; MARTINS, Milton de Arruda; LAGO, Joao Henrique Ghilardi; RIGHETTI, Renato Fraga; PRADO, Carla MaximoBackground and purpose: Asthma is a disease of high prevalence and morbidity that generates high costs in hospitalization and treatment. Although the airway is involved in the physiopathology of asthma, there is also evidence of the importance of vascular and lung parenchyma inflammation and remodeling, which can contribute to the functional pulmonary alterations observed in asthmatic patients. Our aim was to evaluate treatment using sakuranetin, a flavone isolated from the twigs of Baccharis retusa (Asteraceae), on vascular and lung parenchyma alterations in an experimental murine model of asthma. Methods: Male BALB/c mice were subjected to a sensitization protocol with ovalbumin for 30 days and were treated with or without sakuranetin (20 mg/kg/mice) or dexamethasone (5 mg/kg/mice); then, the lungs were collected for histopathological analysis. We evaluated extracellular matrix remodeling (collagen and elastic fibers), inflammation (eosinophils and NF-kB) and oxidative stress (8-isoprostane) in the pulmonary vessels and lung parenchyma. The thickness of the vascular wall was quantified, as well as the vascular endothelial growth factor (VEGF) levels. Results: We demonstrated that sakuranetin reduced the number of eosinophils and elastic fibers in both the pulmonary vessels and the lung parenchyma, probably due to a reduction of oxidative stress and of the transcription factor NF-kB and VEGF levels in the lung. In addition, it reduced the thickness of the pulmonary vascular wall. The treatment had no effect on the collagen fibers. In most of the parameters, the effect of sakuranetin was similar to the dexamethasone effect. Conclusions and implications: Sakuranetin had anti-inflammatory and antioxidant effects, preventing vascular and distal parenchyma changes in this experimental model of asthma.
- Sakuranetin treatment from baccharis retusa reduces acid mucus in a murine model of asthma(2016) SANTANA, Fernanda Paula Roncon; RAMOS, Thais Lourenco; TAVARES, Anna Carolina Morais; PINHEIROS, Nathalia Montouro; SADOKA, Camila Pivari Pedroso; GRECCO, Simone Dos Santos; MACCHIONE, Mariangela; YOSHIZAKI, Kelly; TIBERIO, Iolanda De Fatima Lopes Calvo; MARTINS, Milton de Arruda; LAGO, Joao Henrique Ghilardi; TOLEDO, Alessandra Choqueta; PRADO, Carla Maximo
- A flavanone from Baccharis retusa (Asteraceae) prevents elastase-induced emphysema in mice by regulating NF-kappa B, oxidative stress and metalloproteinases (vol 16, 79, 2015)(2015) TAGUCHI, Laura; PINHEIRO, Nathalia M.; OLIVO, Clarice R.; CHOQUETA-TOLEDO, Alessandra; GRECCO, Simone S.; LOPES, Fernanda D. T. Q. S.; CAPERUTO, Luciana C.; MARTINS, Milton A.; TIBERIO, Iolanda F. L. C.; CAMARA, Niels O.; LAGO, Joao Henrique G.; PRADO, Carla M.
- A flavanone from Baccharis retusa (Asteraceae) prevents elastase-induced emphysema in mice by regulating NF-kappa B, oxidative stress and metalloproteinases(2015) TAGUCHI, Laura; PINHEIRO, Nathalia M.; OLIVO, Clarice R.; CHOQUETA-TOLEDO, Alessandra; GRECCO, Simone S.; LOPES, Fernanda D. T. Q. S.; CAPERUTO, Luciana C.; MARTINS, Milton A.; TIBERIO, Iolanda F. L. C.; CAMARA, Niels O.; LAGO, Joao Henrique G.; PRADO, Carla M.Background: Pulmonary emphysema is characterized by irreversible airflow obstruction, inflammation, oxidative stress imbalance and lung remodeling, resulting in reduced lung function and a lower quality of life. Flavonoids are plant compounds with potential anti-inflammatory and antioxidant effects that have been used in folk medicine. Our aim was to determine whether treatment with sakuranetin, a flavonoid extracted from the aerial parts of Baccharis retusa, interferes with the development of lung emphysema. Methods: Intranasal saline or elastase was administered to mice; the animals were then treated with sakuranetin or vehicle 2 h later and again on days 7, 14 and 28. We evaluated lung function and the inflammatory profile in bronchoalveolar lavage fluid (BALF). The lungs were removed to evaluate alveolar enlargement, extracellular matrix fibers and the expression of MMP-9, MMP-12, TIMP-1, 8-iso-PGF-2 and p65-NF-kappa B in the fixed tissues as well as to evaluate cytokine levels and p65-NF-kappa B protein expression. Results: In the elastase-treated animals, sakuranetin treatment reduced the alveolar enlargement, collagen and elastic fiber deposition and the number of MMP-9- and MMP-12-positive cells but increased TIMP-1 expression. In addition, sakuranetin treatment decreased the inflammation and the levels of TNF-alpha, IL-1 beta and M-CSF in the BALF as well as the levels of NF-kappa B and 8-iso-PGF-2 alpha in the lungs of the elastase-treated animals. However, this treatment did not affect the changes in lung function. Conclusion: These data emphasize the importance of oxidative stress and metalloproteinase imbalance in the development of emphysema and suggest that sakuranetin is a potent candidate that should be further investigated as an emphysema treatment. This compound may be useful for counteracting lung remodeling and oxidative stress and thus attenuating the development of emphysema.
- Flavonone treatment reverses airway inflammation and remodelling in an asthma murine model(2013) TOLEDO, A. C.; SAKODA, C. P. P.; PERINI, A.; PINHEIRO, N. M.; MAGALHAES, R. M.; GRECCO, S.; TIBERIO, I. F. L. C.; CAMARA, N. O.; MARTINS, M. A.; LAGO, J. H. G.; PRADO, C. M.Background and Purpose Asthma is an inflammatory disease that involves airway hyperresponsiveness and remodelling. Flavonoids have been associated to anti-inflammatory and antioxidant activities and may represent a potential therapeutic treatment of asthma. Our aim was to evaluate the effects of the sakuranetin treatment in several aspects of experimental asthma model in mice. Experimental Approach Male BALB/c mice received ovalbumin (i.p.) on days 0 and 14, and were challenged with aerolized ovalbumin 1% on days 24, 26 and 28. Ovalbumin-sensitized animals received vehicle (saline and dimethyl sulfoxide, DMSO), sakuranetin (20mg kg1 per mice) or dexamethasone (5mg kg1 per mice) daily beginning from 24th to 29th day. Control group received saline inhalation and nasal drop vehicle. On day 29, we determined the airway hyperresponsiveness, inflammation and remodelling as well as specific IgE antibody. RANTES, IL-5, IL-4, Eotaxin, IL-10, TNF-, IFN- and GMC-SF content in lung homogenate was performed by Bioplex assay, and 8-isoprostane and NF-kB activations were visualized in inflammatory cells by immunohistochemistry. Key Results We have demonstrated that sakuranetin treatment attenuated airway hyperresponsiveness, inflammation and remodelling; and these effects could be attributed to Th2 pro-inflammatory cytokines and oxidative stress reduction as well as control of NF-kB activation. Conclusions and Implications These results highlighted the importance of counteracting oxidative stress by flavonoids in this asthma model and suggest sakuranetin as a potential candidate for studies of treatment of asthma.