ALESSANDRA CHOQUETA DE TOLEDO ARRUDA
Projetos de Pesquisa
Unidades Organizacionais
LIM/20 - Laboratório de Terapêutica Experimental, Hospital das Clínicas, Faculdade de Medicina
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- 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.
- Time-course effects of aerobic physical training in the prevention of cigarette smoke-induced COPD(2017) TOLEDO-ARRUDA, Alessandra C.; VIEIRA, Rodolfo P.; GUARNIER, Flavia A.; SUEHIRO, Camila L.; CALEMAN-NETO, Agostinho; OLIVO, Clarice R.; ARANTES, Petra M. M.; ALMEIDA, Francine M.; LOPES, Fernanda D. T. Q. S.; RAMOS, Ercy M. C.; CECCHINI, Rubens; LIN, Chin Jia; MARTINS, Milton ArrudaA previous study by our group showed that regular exercise training (ET) attenuated pulmonary injury in an experimental model of chronic exposure to cigarette smoke (CS) in mice, but the time-course effects of the mechanisms involved in this protection remain poorly understood. We evaluated the temporal effects of regular ET in an experimental model of chronic CS exposure. Male C57BL/6 mice were divided into four groups: Control (sedentary + air), Exercise (aerobic training + air), Smoke (sedentary + smoke), and Smoke + Exercise (aerobic training + smoke). Mice were exposed to CS and ET for 4, 8, or 12 wk. Exercise protected mice exposed to CS from emphysema and reductions in tissue damping and tissue elastance after 12 wk (P < 0.01). The total number of inflammatory cells in the bronchoalveolar lavage increased in the Smoke group, mainly due to the recruitment of macrophages after 4 wk, neutrophils and lymphocytes after 8 wk, and lymphocytes and macrophages after 12 wk (P < 0.01). Exercise attenuated this increase in mice exposed to CS. The protection conferred by exercise was mainly observed after exercise adaptation. Exercise increased IL-6 and IL-10 in the quadriceps and lungs (P < 0.05) after 12 wk. Total antioxidant capacity and SOD was increased and TNF-alpha and oxidants decreased in lungs of mice exposed to CS after 12 wk (P < 0.05). The protective effects of exercise against lung injury induced by cigarette smoke exposure suggests that anti-inflammatory mediators and antioxidant enzymes play important roles in chronic obstructive pulmonary disease development mainly after the exercise adaptation. NEW & NOTEWORTHY These experiments investigated for the first time the temporal effects of regular moderate exercise training in cigarette smoke-induced chronic obstructive pulmonary disease. We demonstrate that aerobic conditioning had a protective effect in emphysema development induced by cigarette smoke exposure. This effect was most likely secondary to an effect of exercise on oxidant-antioxidant balance and anti-inflammatory mediators.
- 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.