ALESSANDRA CHOQUETA DE TOLEDO ARRUDA

(Fonte: Lattes)
Índice h a partir de 2011
16
Projetos de Pesquisa
Unidades Organizacionais
LIM/20 - Laboratório de Terapêutica Experimental, Hospital das Clínicas, Faculdade de Medicina

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Agora exibindo 1 - 10 de 25
  • 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.
  • article 10 Citação(ões) na Scopus
    Aerobic exercise modulates cardiac NAD(P)H oxidase and the NRF2/KEAP1 pathway in a mouse model of chronic fructose consumption
    (2020) ALVES, Renata; SUEHIRO, Camila Liyoko; OLIVEIRA, Flavia Garcia de; FRANTZ, Eliete Dalla Corte; MEDEIROS, Renata Frauches de; VIEIRA, Rodolfo de Paula; MARTINS, Milton de Arruda; LIN, Chin Jia; NOBREGA, Antonio Claudio Lucas da; TOLEDO-ARRUDA, Alessandra Choqueta de
    The present study investigated the effects of exercise on the cardiac nuclear factor (erythroid-derived 2) factor 2 (NRF2)/Kelch-like ECU-associated protein 1 (KEAP1) pathway in an experimental model of chronic fructose consumption. Male C57BL/6 mice were assigned to Control, Fructose (20% fructose in drinking water), Exercise (treadmill exercise at moderate intensity), and Fructose + Exercise groups (n = 10). After 12 wk. the energy intake and body weight in the groups were similar. Maximum exercise testing, resting energy expenditure, resting oxygen consumption, and carbon dioxide production increased in the exercise groups (Exercise and Fructose + Exercise vs. Control and Fructose groups. P < 0.05). Chronic fructose intake induced circulating hypercholesterolemia, hypertriglyceridemia. and hyperleptinemia and increased white adipose tissue depots, with no changes in blood pressure. This metabolic environment increased circulating IL-6, IL-1 beta, IL-10, cardiac hypertrophy. and cardiac NF-kappa B-p65 and TNF-alpha expression, which were reduced by exercise (P < 0.05). Cardiac ANC. II type 1 receptor and NiD(P)H oxidase 2 (NOX2) were increased by fructose intake and exercise decreased this response (P < 0.05). Exercise increased the cardiac expression of the NRF2-to-KEAP1 ratio and phase II antioxidants in fructose-fed mice (P < 0.05). NOX4, glutathione reductase, and catalase protein expression were similar between the groups. These findings suggest that exercise confers modulatory cardiac effects, improving antioxidant defenses through the NRF2/KEAP1 pathway and decreasing oxidative stress, representing a potential nonpharmacological approach to protect against fructose-induced cardiometabolic diseases. NEW & NOTEWORTHY This is the first study to evaluate the cardiac modulation of NAD(P)H oxidase (NOX), the NRF2/Kelchlike ECH-associated protein 1 pathway (KEAP), and the thioredoxin TRX1) system through exercise in the presence of moderate fructose intake. We demonstrated a novel mechanism by which exercise improves cardiac antioxidant defenses in an experimental model of chronic fructose intake, which involves NRF2-to-KEAP1 ratio modulation, enhancing the local phase II antioxidants hemoxygenase-1, thioredoxin reductase (TXNRD1), and peroxiredoxin1B (PDRX1), and inhibiting cardiac NOX2 overexpression.
  • article 62 Citação(ões) na Scopus
    The effects of elastic tubing-based resistance training compared with conventional resistance training in patients with moderate chronic obstructive pulmonary disease: a randomized clinical trial
    (2014) RAMOS, Ercy Mara Cipulo; TOLEDO-ARRUDA, Alessandra Choqueta de; FOSCO, Luciana Cristina; BONFIM, Rafaela; BERTOLINI, Giovana Navarro; GUARNIER, Flavia Alessandra; CECCHINI, Rubens; PASTRE, Carlos Marcelo; LANGER, Daniel; GOSSELINK, Rik; RAMOS, Dionei
    Objective: To investigate the effects of elastic tubing training compared with conventional resistance training on the improvement of functional exercise capacity, muscle strength, fat-free mass, and systemic inflammation in patients with chronic obstructive pulmonary disease. Design: A prospective, randomized, eight-week clinical trial. Setting: The study was conducted in a university-based, outpatient, physical therapy clinic. Subjects: A total of 49 patients with moderate chronic obstructive pulmonary disease. Interventions: Participants were randomly assigned to perform elastic tubing training or conventional resistance training three times per week for eight weeks. Main measures: The primary outcome measure was functional exercise capacity. The secondary outcome measures were peripheral muscle strength, health-related quality of life assessed by the Chronic Respiratory Disease Questionnaire (CRDQ), fat-free mass, and cytokine profile. Results: After eight weeks, the mean distance covered during six minutes increased by 73 meters (69) in the elastic tubing group and by 42 meters (+/- 59) in the conventional group (p < 0.05). The muscle strength and quality of life improved in both groups (P < 0.05), with no significant differences between the groups. There was a trend toward an improved fat-free mass in both groups (P = 0.05). After the first and last sessions, there was an increase in interleukin 1 (IL-1) and interleukin 10 (IL-10) in both groups, while tumour necrosis factor alpha (TNF-) was stimulated only in the conventional training group. Conclusion: Elastic tubing training had a greater effect on functional exercise capacity than conventional resistance training. Both interventions were equally effective in improving muscle strength and quality of life.
  • article 15 Citação(ões) na Scopus
    Nasal Mucociliary Clearance in Subjects With COPD After Smoking Cessation
    (2015) ITO, Juliana T.; RAMOS, Dionei; LIMA, Fabiano F.; RODRIGUES, Fernanda M. M.; GOMES, Paulo R.; MOREIRA, Graciane L.; MACCHIONE, Mariangela; TOLEDO, Alessandra C.; RAMOS, Ercy M. C.
    BACKGROUND: Exposure to cigarette smoke causes significant impairment in mucociliary clearance (MCC), which predisposes patients to secretion retention and recurrent airway infections that play a role in exacerbations of COPD. To determine whether smoking cessation may influence MCC and frequency of exacerbations, the following groups were evaluated: ex-smokers with COPD, smokers with COPD, current smokers with normal lung function, and nonsmokers with normal lung function. METHODS: Ninety-three subjects were divided into 4 groups: ex-smokers with COPD (n = 23, 62.4 +/- 8.0 y, 13 males), smokers with COPD (n = 17, 58.2 +/- 8.0 y, 6 males), current smokers (n = 27, 61.5 +/- 6.4 y, 17 males), and nonsmokers (n = 26, 60.8 +/- 11.3 y, 7 males). MCC was evaluated using the saccharin transit time (STT) test, and the frequency of exacerbations in the last year was assessed by questionnaire. The Kruskal-Wallis test followed by Dunn's test were used to compare STT among groups, and the Goodman test was used to compare the frequency of exacerbations. RESULTS: STT of smokers with COPD (16.5 [11-28] min; median [interquartile range 25-75%]) and current smokers (15.9 110-271 min) was longer compared with ex-smokers with COPD (9.7 [6-12] min) and nonsmokers (8 [6-16] min) (P < .001). There was no difference in STT values between smokers with COPD and current smokers, and these values in ex-smokers with COPD were similar to the control group (P > .05). The frequency of exacerbations was lower in ex-smokers with COPD compared with smokers with COPD. CONCLUSIONS: One year after smoking cessation, subjects with COPD had improved mucociliary clearance.
  • article 10 Citação(ões) na Scopus
    Enriched inorganic compounds in diesel exhaust particles induce mitogen-activated protein kinase activation, cytoskeleton instability, and cytotoxicity in human bronchial epithelial cells
    (2015) SERIANI, Robson; JUNQUEIRA, Mara S.; CARVALHO-SOUSA, Claudia E.; ARRUDA, Alessandra Ct.; MARTINEZ, Diana; ALENCAR, Adriano M.; GARIPPO, Ana L.; BRITO, Jose Mara; MARTINS, Milton A.; SALDIVA, Paulo H. N.; NEGRI, Elnara M.; MAUAD, Thais; MACCHIONE, Mariangela
    This study assessed the effects of the diesel exhaust particles on ERR and JNK MAPKs activation, cell rheology (viscoelasticity), and cytotoxicity in bronchial epithelial airway cells (BEAS-2B). Crude DEP and DEP after extraction with hexane (DEP/HEX) were utilized. The partial reduction of some DEP/HEX organics increased the biodisponibility of many metallic elements. JNK and ERR were activated simultaneously by crude DEP with no alterations in viscoelasticity of the cells. Mitochondrial activity, however, revealed a decrease through the MIT assay. DEP/HEX treatment increased viscoelasticity and cytotoxicity (membrane damage), and also activated JNK. Our data suggest that the greater bioavailability of metals could be involved in JNK activation and, consequently, in the reduction of fiber coherence and increase in the viscoelasticity and cytotoxicity of BEAS cells. The adverse findings detected after exposure to crude DEP and to DEP/HEX reflect the toxic potential of diesel compounds. Considering the fact that the cells of the respiratory epithelium are the first line of defense between the body and the environment, our data contribute to a better understanding of the pathways leading to respiratory cell injury and provide evidence for the onset of or worsening of respiratory diseases caused by inorganic compounds present in DEP.
  • article 66 Citação(ões) na Scopus
    Anti-inflammatory Effects of Aerobic Exercise in Mice Exposed to Air Pollution
    (2012) VIEIRA, Rodolfo de Paula; TOLEDO, Alessandra Choqueta; SILVA, Lucas Bogaz; ALMEIDA, Francine Maria; DAMACENO-RODRIGUES, Nilsa Regina; CALDINI, Elia Garcia; SANTOS, Angela Batista Gomes; RIVERO, Dolores Helena; HIZUME, Deborah Camargo; LOPES, Fernanda Degobbi Tenorio Quirino Santos; OLIVO, Clarice Rosa; CASTRO-FARIA-NETO, Hugo Caire; MARTINS, Milton Arruda; SALDIVA, Paulo Hilario Nascimento; DOLHNIKOFF, Marisa
    Purpose: Exposure to diesel exhaust particles (DEP) results in lung inflammation. Regular aerobic exercise improves the inflammatory status in different pulmonary diseases. However, the effects of long-term aerobic exercise on the pulmonary response to DEP have not been investigated. The present study evaluated the effect of aerobic conditioning on the pulmonary inflammatory and oxidative responses of mice exposed to DEP. Methods: BALB/c mice were subjected to aerobic exercise five times per week for 5 wk, concomitantly with exposure to DEP (3 mg.mL (1); 10 mu L per mouse). The levels of exhaled nitric oxide, reactive oxygen species, cellularity, interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) were analyzed in bronchoalveolar lavage fluid, and the density of neutrophils and the volume proportion of collagen fibers were measured in the lung parenchyma. The cellular density of leukocytes expressing IL-1 beta, keratinocyte chemoattractant (KC), and TNF-alpha in lung parenchyma was evaluated with immunohistochemistry. The levels of IL-1 beta, KC, and TNF-alpha were also evaluated in the serum. Results: Aerobic exercise inhibited the DEP-induced increase in the levels of reactive oxygen species (P < 0.05); exhaled nitric oxide (P < 0.01); total (P < 0.01) and differential cells (P < 0.01); IL-6 and TNF-alpha levels in bronchoalveolar lavage fluid (P < 0.05); the level of neutrophils (P < 0.001); collagen density in the lung parenchyma (P < 0.05); the levels of IL-6, KC, and TNF-alpha in plasma (P < 0.05); and the expression of IL-1 beta, KC, and TNF-alpha by leukocytes in the lung parenchyma (P < 0.01). Conclusions: We conclude that long-term aerobic exercise presents protective effects in a mouse model of DEP-induced lung inflammation. Our results indicate a need for human studies that evaluate the pulmonary responses to aerobic exercise chronically performed in polluted areas.
  • article 7 Citação(ões) na Scopus
    Acute Mucociliary Clearance Response to Aerobic Exercise in Smokers
    (2015) RAMOS, Ercy M. C.; VANDERLEI, Luiz Carlos M.; ITO, Juliana T.; LIMA, Fabiano F.; RODRIGUES, Fernanda M. M.; MANZANO, Beatriz M.; FERNANDES, Romulo A.; CECILIO, Michel J.; TOLEDO-ARRUDA, Alessandra C.; RAMOS, Dionei
    BACKGROUND: Mucociliary clearance is the main defense mechanism of the respiratory system, and it is influenced by several stimuli, including aerobic exercise and cigarette smoking. We evaluated the acute response of mucociliary clearance to aerobic exercise in smokers and nonsmokers compared with that found after acute smoking and smoking combined with exercise. Also, we investigated whether there was a correlation between mucociliary clearance and the autonomic nervous system under these conditions. METHODS: Twenty-one smokers were evaluated for mucociliary clearance by saccharin transit time (STT), and the response of the autonomic nervous system was evaluated by heart rate variability after aerobic exercise, after exercise followed by smoking, after acute smoking, and after rest. For comparison, 17 nonsmokers were also assessed during exercise. Repeated-measures analysis of variance with the Tukey test or the Friedman test followed by the Dunn test was used to evaluate the STT, autonomic response, and other variables to exercise and/or smoking in smokers. A paired t test or Wilcoxon test was used to analyze responses to exercise in nonsmokers. Correlations were evaluated using Pearson or Spearman coefficients. RESULTS: The STT was reduced after exercise in both groups, with similar responses between them. Other stimuli also reduced the STT. The STT showed a negative correlation with sympathetic activity in smokers and a positive correlation with the parasympathetic system in nonsmokers. CONCLUSIONS: Although impaired in smokers, mucociliary clearance responded to the stimulus of exercise, as demonstrated by similar STTs compared with nonsmokers. This response was correlated with the autonomic nervous system in both groups. In smokers, mucociliary clearance also responded to the stimuli of smoking and exercise followed by smoking.
  • article 9 Citação(ões) na Scopus
    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, Dionei
    OBJECTIVE: 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.
  • article 16 Citação(ões) na Scopus
    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.
  • article 24 Citação(ões) na Scopus
    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 Maximo
    Background 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.