ALESSANDRA CHOQUETA DE TOLEDO ARRUDA
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LIM/20 - Laboratório de Terapêutica Experimental, Hospital das Clínicas, Faculdade de Medicina
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article 31 Citação(ões) na Scopus Short-term exposure of mice to cigarette smoke and/or residual oil fly ash produces proximal airspace enlargements and airway epithelium remodeling(2011) BISELLI, P. J. C.; LOPES, F. D. T. Q. S.; MORIYA, H. T.; RIVERO, D. H. R. F.; TOLEDO, A. C.; SALDIVA, P. H. N.; MAUAD, T.; MARTINS, A.Chronic obstructive pulmonary disease (COPD) is associated with inflammatory cell reactions, tissue destruction and lung remodeling. Many signaling pathways for these phenomena are still to be identified. We developed a mouse model of COPD to evaluate some pathophysiological mechanisms acting during the initial stage of the disease. Forty-seven 6- to 8-week-old female C57/BL6 mice (approximately 22 g) were exposed for 2 months to cigarette smoke and/or residual oil fly ash (ROFA), a concentrate of air pollution. We measured lung mechanics, airspace enlargement, airway wall thickness, epithelial cell profile, elastic and collagen fiber deposition, and by immunohistochemistry transforming growth factor-beta 1 (TGF-beta 1), macrophage elastase (MMP12), neutrophils and macrophages. We observed regional airspace enlargements near terminal bronchioles associated with the exposure to smoke or ROFA. There were also increases in airway resistance and thickening of airway walls in animals exposed to smoke. In the epithelium, we noted a decrease in the ciliated cell area of animals exposed to smoke and an increase in the total cell area associated with exposure to both smoke and ROFA. There was also an increase in the expression of TGF-beta 1 both in the airways and parenchyma of animals exposed to smoke. However, we could not detect inflammatory cell recruitment, increases in MMP12 or elastic and collagen fiber deposition. After 2 months of exposure to cigarette smoke and/or ROFA, mice developed regional airspace enlargements and airway epithelium remodeling, although no inflammation or increases in fiber deposition were detected. Some of these phenomena may have been mediated by TGF-beta 1.- 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.
- Avaliação da qualidade de vida relacionada à saúde de cortadores de cana-de-açúcar nos períodos de entressafra e safra(2012) CARVALHO JUNIOR, Luiz Carlos Soares de; RAMOS, Ercy Mara Cipulo; TOLEDO, Alessandra Choqueta de; CECCATO, Aline Duarte Ferreira; MACCHIONE, Mariangela; BRAGA, Alfesio Luis Ferreira; RAMOS, DioneiOBJECTIVE: To assess health-related quality of life in sugarcane cutters. METHODS: Longitudinal study conducted in a sugar and ethanol plant located in the western region of the State of Sao Paulo (Southeastern Brazil) from April (pre-harvest) to October (harvest) 2010. A total of 44 sugarcane cutters, smokers and non-smokers, was evaluated in three periods: pre-harvest, at the end of the third month during harvest and at the end of harvest. Health-related quality of life was assessed by the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). Analysis of variance for repeated measures and the Friedman test were performed to compare quality of life among the periods. To identify the frequency of workers whose score increased in the harvest periods compared to pre-harvest (positive responders), the Goodman test was used, considering the qualitative variables of the SF-36 domains. RESULTS: At the end of pre-harvest, 23% workers drop out of work; 27% were smokers. There was a significant decrease in the vitality domain at the end of harvest compared to pre-harvest. The dropouts presented higher score in the social aspect domain compared to the group that remained working. There was no difference in health-related quality of life between smokers and non-smokers. However, there was a higher percentage of positive responders among non-smokers in the physical, social and emotional domains in the third month of harvest and in the general health status and social domains at the end of harvest, compared to smokers. CONCLUSIONS: Health-related quality of life in sugarcane cutters was reduced after the harvest period in the vitality domain. The individuals who remained working during harvest are those with lower scores for social aspects, which demonstrates the need to promote health assistance policies for this specific population, particularly during sugar harvest.
- 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.
- Analysis of autonomic modulation after an acute session of resistance exercise at different intensities in chronic obstructive pulmonary disease patients(2015) NICOLINO, Juliana; RAMOS, Dionei; LEITE, Marceli Rocha; RODRIGUES, Fernanda Maria Machado; SILVA, Bruna Spolador de Alencar; TACAO, Guilherme Yassuyuki; TOLEDO, Alessandra Choqueta de; VANDERLEI, Luiz Carlos Marques; RAMOS, Ercy Mara CipuloPurpose: Physical exercises are employed as part of the treatment of patients with chronic obstructive pulmonary disease (COPD); however information regarding cardiac autonomic modulation after an acute session of resistance exercise (RE) is unknown. The aim of this study was to evaluate the cardiac autonomic modulation, via heart rate variability after an acute session of RE applied at different intensities in COPD patients. Patients and methods: Twelve COPD patients underwent an acute session of RE with an intensity of 600% and another of 9000 of the one repetition maximum test. For analysis of autonomic modulation, heart rate was recorded beat-by-beat for 20 minutes at rest and after the training session. Heart rate variability indexes were obtained in the time and frequency domains for the assessment of autonomic modulation. Results: Regardless of exercise intensity, RE acute sessions influenced the autonomic modulation the recovery period was compared with the baseline. An increase in standard deviation of normal to normal RR intervals was observed throughout recovery time after the RE, as compared to baseline in both protocols: 60% and 90% of the one repetition maximum test. The spectral component of low frequency index (ms) was higher throughout recovery when compared to baseline in both protocols. The same was also observed in the spectral component of high frequency index (ms) for the protocols of 60% and 90%. Conclusion: RE sessions impact on the autonomic modulation of COPD patients by promoting differences in the recovery period compared to baseline, regardless of the intensity of the exercise performed.
- Chronic exposure of diesel exhaust particles induces alveolar enlargement in mice(2015) YOSHIZAKI, Kelly; BRITO, Jose Mara; MORIYA, Henrique T.; TOLEDO, Alessandra C.; FERZILAN, Sandra; OLIVEIRA, Ana Paula Ligeiro de; MACHADO, Isabel D.; FARSKY, Sandra H. P.; SILVA, Luiz F. F.; MARTINS, Milton A.; SALDIVA, Paulo H. N.; MAUAD, Thais; MACCHIONE, MariangelaBackground: Diesel exhaust particles (DEPs) are deposited into the respiratory tract and are thought to be a risk factor for the development of diseases of the respiratory system. In healthy individuals, the timing and mechanisms of respiratory tract injuries caused by chronic exposure to air pollution remain to be clarified. Methods: We evaluated the effects of chronic exposure to DEP at doses below those found in a typical bus corridor in Sao Paulo (150 mu g/m(3)). Male BALB/c mice were divided into mice receiving a nasal instillation: saline (saline; n = 30) and 30 mu g/10 mu L of DEP (DEP; n = 30). Nasal instillations were performed five days a week, over a period of 90 days. Bronchoalveolar lavage (BAL) was performed, and the concentrations of interleukin (IL)-4, IL-10, IL-13 and interferon-gamma (INF-gamma) were determined by ELISA-immunoassay. Assessment of respiratory mechanics was performed. The gene expression of Muc5ac in lung was evaluated by RT-PCR. The presence of IL-13, MAC2+ macrophages, CD3+, CD4+, CD8+ T cells and CD20+ B cells in tissues was analysed by immunohistochemistry. Bronchial thickness and the collagen/elastic fibers density were evaluated by morphometry. We measured the mean linear intercept (Lm), a measure of alveolar distension, and the mean airspace diameter (D0) and statistical distribution (D2). Results: DEP decreased IFN-gamma levels in BAL (p = 0.03), but did not significantly alter IL-4, IL-10 and IL-13 levels. MAC2+ macrophage, CD4+ T cell and CD20+ B cell numbers were not altered; however, numbers of CD3+ T cells (p <= 0.001) and CD8+ T cells (p <= 0.001) increased in the parenchyma. Although IL-13 (p = 0.008) expression decreased in the bronchiolar epithelium, Muc5ac gene expression was not altered in the lung of DEP-exposed animals. Although respiratory mechanics, elastic and collagen density were not modified, the mean linear intercept (Lm) was increased in the DEP-exposed animals (p <= 0.001), and the index D2 was statistically different (p = 0.038) from the control animals. Conclusion: Our data suggest that nasal instillation of low doses of DEP over a period of 90 days results in alveolar enlargement in the pulmonary parenchyma of healthy mice.
- 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.
- Exercise Inhibits the Effects of Smoke-Induced COPD Involving Modulation of STAT3(2017) BRANDAO-RANGEL, Maysa Alves Rodrigues; BACHI, Andre Luis Lacerda; OLIVEIRA-JUNIOR, Manoel Carneiro; ABBASI, Asghar; SILVA-RENNO, Adriano; BRITO, Aurileia Aparecida de; OLIVEIRA, Ana Paula Ligeiro de; TOLEDO-ARRUDA, Alessandra Choqueta; BELVISI, Maria Gabriela; VIEIRA, Rodolfo PaulaPurpose. Evaluate the participation of STAT3 in the effects of aerobic exercise (AE) in a model of smoke-induced COPD. Methods. C57Bl/6 male mice were divided into control, Exe, COPD, and COPD+ Exe groups. Smoke were administered during 90 days. Treadmill aerobic training begun on day 61 until day 90. Pulmonary inflammation, systemic inflammation, the level of lung emphysema, and the airway remodeling were evaluated. Analysis of integral and phosphorylated expression of STAT3 by airway epithelial cells, peribronchial leukocytes, and parenchymal leukocytes was performed. Results. AE inhibited smoke-induced accumulation of total cells (p < 0 001), lymphocytes (p < 0 001), and neutrophils (p < 0 001) in BAL, as well as BAL levels of IL-1 beta (p < 0 001), CXCL1 (p < 0 001), IL-17 (p < 0 001), and TNF-alpha (p < 0 05), while increased the levels of IL-10 (p < 0 001). AE also inhibited smoke-induced increases in total leukocytes (p < 0 001), neutrophils (p < 0 05), lymphocytes (p < 0 001), and monocytes (p < 0 01) in blood, as well as serum levels of IL-1 beta (p < 0 01), CXCL1 (p < 0 01), IL-17 (p < 0 05), and TNF-a (p < 0 01), while increased the levels of IL-10 (p < 0 001). AE reduced smoke-induced emphysema (p < 0 001) and collagen fiber accumulation in the airways (p < 0 001). AE reduced smoke-induced STAT3 and phospho-STAT3 expression in airway epithelial cells (p < 0 001), peribronchial leukocytes (p < 0 001), and parenchymal leukocytes (p < 0 001). Conclusions. AE reduces smoke-induced COPD phenotype involving STAT3.
- Effects of 12 weeks of aerobic training on autonomic modulation, mucociliary clearance, and aerobic parameters in patients with COPD(2015) LEITE, Marceli Rocha; RAMOS, Ercy Mara Cipulo; KALVA-FILHO, Carlos Augusto; FREIRE, Ana Paula Coelho Figueira; SILVA, Bruna Spolador de Alencar; NICOLINO, Juliana; TOLEDO-ARRUDA, Alessandra Choqueta de; PAPOTI, Marcelo; VANDERLEI, Luiz Carlos Marques; RAMOS, DioneiIntroduction: Patients with chronic obstructive pulmonary disease (COPD) exhibit aerobic function, autonomic nervous system, and mucociliary clearance alterations. These parameters can be attenuated by aerobic training, which can be applied with continuous or interval efforts. However, the possible effects of aerobic training, using progressively both continuous and interval sessions (ie, linear periodization), require further investigation. Aim: To analyze the effects of 12-week aerobic training using continuous and interval sessions on autonomic modulation, mucociliary clearance, and aerobic function in patients with COPD. Methods: Sixteen patients with COPD were divided into an aerobic (continuous and interval) training group (AT) (n= 10) and a control group (CG) (n= 6). An incremental test (initial speed of 2.0 km.h(-1), constant slope of 3%, and increments of 0.5 km.h(-1) every 2 minutes) was performed. The training group underwent training for 4 weeks at 60% of the peak velocity reached in the incremental test (vVO(2peak)) (50 minutes of continuous effort), followed by 4 weeks of sessions at 75% of vVO(2peak) (30 minutes of continuous effort), and 4 weeks of interval training (5x3-minute effort at vVO(2peak), separated by 1 minute of passive recovery). Intensities were adjusted through an incremental test performed at the end of each period. Results: The AT presented an increase in the high frequency index (ms(2)) (P= 0.04), peak oxygen uptake (VO2peak) (P= 0.01), vVO(2peak) (P= 0.04), and anaerobic threshold (P= 0.02). No significant changes were observed in the CG (P > 0.21) group. Neither of the groups presented changes in mucociliary clearance after 12 weeks (AT: P= 0.94 and CG: P= 0.69). Conclusion: Twelve weeks of aerobic training (continuous and interval sessions) positively influenced the autonomic modulation and aerobic parameters in patients with COPD. However, mucociliary clearance was not affected by aerobic training.