FERNANDA DEGOBBI TENORIO QUIRINO DOS SANTOS LOPES
Projetos de Pesquisa
Unidades Organizacionais
LIM/20 - Laboratório de Terapêutica Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/05 - Laboratório de Poluição Atmosférica 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.- Th17/Treg-Related Intracellular Signaling in Patients with Chronic Obstructive Pulmonary Disease: Comparison between Local and Systemic Responses(2021) LOURENCO, Juliana D.; TEODORO, Walcy R.; BARBEIRO, Denise F.; VELOSA, Ana Paula P.; SILVA, Larissa E. F.; KOHLER, Julia B.; MOREIRA, Alyne R.; V, Marcelo Aun; SILVA, Isadora C. da; FERNANDES, Frederico L. A.; NEGRI, Elnara M.; GROSS, Jefferson L.; TIBERIO, Iolanda F. L. C.; ITO, Juliana T.; LOPES, Fernanda D. T. Q. S.Th17/Treg imbalance plays a pivotal role in COPD development and progression. We aimed to assess Th17/Treg-related intracellular signaling at different COPD stages in local and systemic responses. Lung tissue and/or peripheral blood samples were collected and divided into non-obstructed (NOS), COPD stages I and II, and COPD stages III and IV groups. Gene expression of STAT3 and -5, ROR gamma t, Foxp3, interleukin (IL)-6, -17, -10, and TGF-beta was assessed by RT-qPCR. IL-6, -17, -10, and TGF-beta levels were determined by ELISA. We observed increased STAT3, ROR gamma t, Foxp3, IL-6, and TGF-beta gene expression and IL-6 levels in the lungs of COPD I and II patients compared to those of NOS patients. Regarding the systemic response, we observed increased STAT3, ROR gamma t, IL-6, and TGF-beta gene expression in the COPD III and IV group and increased IL-6 levels in the COPD I and II group. STAT5 was increased in COPD III and IV patients, although there was a decrease in Foxp3 expression and IL-10 levels in the COPD I and II and COPD III and IV groups, respectively. We demonstrated that an increase in Th17 intracellular signaling in the lungs precedes this increase in the systemic response, whereas Treg intracellular signaling varies between the compartments analyzed in different COPD stages.
- Increased bone resorption by long-term cigarette smoke exposure in animal model(2021) JUNQUEIRA, Jader Joel Machado; LOURENCO, Juliana Dias; SILVA, Kaique Rodrigues da; JORGETTI, Vanda; VIEIRA, Rodolfo P.; ARAUJO, Amanda Aparecida de; ANGELIS, Katia De; CORREIA, Aristides Tadeu; ALVES, Luan Henrique Vasconcelos; TIBERIO, Iolanda de Fatima Lopes Calvo; BARBOSA, Alexandre Povoa; LOPES, Fernanda Degobbi Tenorio Quirino dos SantosIntroduction: Clinical and experimental studies have been attesting the deleterious effects of smoking mainly due to the stimulation of osteoclastogenesis and inhibition of osteoblastogenesis. However the physiological mechanisms that can explain these changes are not fully understood. Aims: To evaluate the trabecular bone resorption effect caused by long-term exposure to cigarette smoke and the action of cytokines and reactive oxygen species involved in this process. Methods: Sixty young adult C57BL/6 mice were allocated to two groups: control, 30 animals exposed to filtered air for 1, 3 and 6 months; and smoke, 30 animals exposed to cigarette smoke for 1, 3 and 6 months. Femoral and tibial extraction was performed to evaluate the bone mineral matrix, bone cytokines (Receptor activator of nuclear factor-kappa B ligand -RANKL and Osteoprotegerin -OPG) and oxidative stress markers (Thiobarbituric acid reactive substances -Tbars). Results: Exposure to cigarette smoke (CS) generated changes in bone structural parameters in the 6th month of follow-up, demonstrating an evident bone loss; reduction in OPG/RANKL ratio from the 3rd month on and increase in Tbars in the first month, both closely related to the increase in osteoclastogenic activity and bone resorption. Conclusion: These findings reinforce the importance of CS-induced oxidative stress in bone compromising the bone cellular activities with a consequent impairment in bone turn over and changes in bone structure.
- Smoking induces increased apoptosis in osteoblasts: changes in bone matrix organic components(2023) KOHLER, Julia Benini; SILVA, Alex Ferreira da; FARIAS, Walleson Alves; SAMPAIO, Barbara Fialho Carvalho; NEVES, Marco Aurelio Silveiro; LIMA, Leandro Gregorut; LOURENCO, Juliana Dias; MOREIRA, Alyne Riani; BARBOSA, Alexandre Povoa; TIBERIO, Iolanda de Fatima Lopes Calvo; TEODORO, Walcy Rosolia; LOPES, Fernanda Degobbi Tenorio Quirino dos SantosClinical studies demonstrate the impact of smoking on bone tissue fragility and higher incidence of fractures. However, it is not totally understood which physiological mechanisms could be involved in these events. Previously, we showed important changes in bone tissue components in experimental model of cigarette smoke (CS) exposure. CS exposure induces worsening in bone mineralization and a decrease in collagen type I deposition, leading to bone fragility. Considering that the majority of clinical studies described bone structural changes by radiographic images, in this study we performed analyses ""in situ"" using tissue samples from smokers, former smokers and non-smokers to better understand how the increase in inflammatory mediators induced by smoking exposure could interfere in bone cells activity leading bone structural changes. We observed increased levels of IL-1 beta, IL-6 and TNF-alpha in bone tissue homogenates with a concomitant increase in osteoblast apoptosis in smokers and former smokers compared with non-smokers. Histological changes in both smokers and former smokers were characterized by reduction in collagen type I. Only in smokers, it was observed decrease in trabecular area, suggesting increased bone resorption and increase in collagen type V. These results showed that osteoblasts apoptosis in association with increased bone resorption leads bone structural changes in smokers.
- Antileukotriene Reverts the Early Effects of Inflammatory Response of Distal Parenchyma in Experimental Chronic Allergic Inflammation(2013) GOBBATO, Nathalia Brandao; SOUZA, Flavia Castro Ribas de; FUMAGALLI, Stella Bruna Napolitano; LOPES, Fernanda Degobbi Tenorio Quirino dos Santos; PRADO, Carla Maximo; MARTINS, Milton Arruda; TIBERIO, Iolanda de Fatima Lopes Calvo; LEICK, Edna AparecidaAims. Compare the effects of montelukast or dexamethasone in distal lung parenchyma and airway walls of guinea pigs (GP) with chronic allergic inflammation. Methods. GP have inhaled ovalbumin (OVA group-2x/week/4weeks). After the 4th inhalation, GP were treated with montelukast or dexamethasone. After 72 hours of the 7th inhalation, GP were anesthetised, and lungs were removed and submitted to histopathological evaluation. Results. Montelukast and dexamethasone treatments reduced the number of eosinophils in airway wall and distal lung parenchyma compared to OVA group (P < 0.05). On distal parenchyma, both treatments were effective in reducing RANTES, NF-kappa B, and fibronectin positive cells compared to OVA group (P < 0.001). Montelukast was more effective in reducing eotaxin positive cells on distal parenchyma compared to dexamethasone treatment (P < 0.001), while there was a more expressive reduction of IGF-I positive cells in OVA-D group (P < 0.001). On airway walls, montelukast and dexamethasone were effective in reducing IGF-I, RANTES, and fibronectin positive cells compared to OVA group (P < 0.05). Dexamethasone was more effective in reducing the number of eotaxin and NF-kappa B positive cells than Montelukast (P < 0.05). Conclusions. In this animal model, both treatments were effective in modulating allergic inflammation and remodeling distal lung parenchyma and airway wall, contributing to a better control of the inflammatory response.
- Respiratory mechanics do not always mirror pulmonary histological changes in emphysema(2011) ANCIAES, Adriana Martins; OLIVO, Clarice Rosa; PRADO, Carla Maximo; KAGOHARA, Keila H.; PINTO, Tatiana da Silva; MORIYA, Henrique T.; MAUAD, Thais; MARTINS, Milton de Arruda; LOPES, Fernanda Degobbi Tenorio Quirino dos SantosOBJECTIVE : To verify the accordance of functional and morphometric parameters during the development of emphysema. METHODS : BALB/c mice received a nasal drop of either papain or saline solution and were studied after 1, 3, 15, 28, and 40 days. Functional parameters, such as airway resistance, tissue damping, and tissue elastance, were analyzed. To evaluate the structural changes and possible mechanisms involved in this disease, we measured the mean linear intercept, the volume proportions of elastic and collagen fibers, the number of macrophages, the numbers of cells expressing metalloprotease 12 and 8-isoprostane in lung parenchyma. RESULTS : We only observed decreases in tissue elastance and tissue damping on the 28(th) day, with a concomitant increase in the mean linear intercept, indicating the presence of emphysema. However, only the mean linear intercept values remained increased until the 40(th) day. The volume proportion of collagen fibers was increased from the 15(th) day to the 40(th) day, whereas the volume proportion of elastic fibers was only increased on the 40(th) day. The number of macrophages increased beginning on the 1(st) day. The expression of metalloproteinase 12 was increased from the 3(rd) day until the 40(th) day. However, 8-isoprostane expression was only increased on the 1(st) and 3(rd) days. CONCLUSIONS : In this study, morphometric parameters were found to be more reliable for detecting the presence of emphysema than the functional parameters measured by respiratory mechanics. Further investigations are necessary to understand how the extracellular matrix remodeling observed in the lung parenchyma could be involved in this process.
- Evidences of Herbal Medicine-Derived Natural Products Effects in Inflammatory Lung Diseases(2016) SANTANA, Fernanda Paula R.; PINHEIRO, Nathalia M.; MERNAK, Marcia Isabel B.; RIGHETTI, Renato F.; MARTINS, Milton A.; LAGO, Joao H. G.; LOPES, Fernanda D. T. Q. dos Santos; TIBERIO, Iolanda F. L. C.; PRADO, Carla M.Pulmonary inflammation is a hallmark of many respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and acute respiratory syndrome distress (ARDS). Most of these diseases are treated with anti-inflammatory therapy in order to prevent or to reduce the pulmonary inflammation. Herbal medicine-derived natural products have been used in folk medicine and scientific studies to evaluate the value of these compounds have grown in recent years. Many substances derived from plants have the biological effects in vitro and in vivo, such as flavonoids, alkaloids, and terpenoids. Among the biological activities of natural products derived from plants can be pointed out the anti-inflammatory, antiviral, antiplatelet, antitumor anti-allergic activities, and antioxidant. Although many reports have evaluated the effects of these compounds in experimental models, studies evaluating clinical trials are scarce in the literature. This review aims to emphasize the effects of these different natural products in pulmonary diseases in experimental models and in humans and pointing out some possible mechanisms of action.
- iNOS Inhibition Reduces Lung Mechanical Alterations and Remodeling Induced by Particulate Matter in Mice(2019) PRADO, Carla Maximo; RIGHETTI, Renato Fraga; LOPES, Fernanda Degobbi Tenorio Quirino dos Santos; LEICK, Edna Aparecida; ARANTES-COSTA, Fernanda Magalhaes; ALMEIDA, Francine Maria de; SALDIVA, Paulo Hilario Nascimento; MAUAD, Thais; TIBERIO, Iolanda de Fatima Lopes Calvo; MARTINS, Milton de ArrudaBackground. The epidemiologic association between pulmonary exposure to ambient particulate matter (PM) and acute lung damage is well known. However, the mechanism involved in the effects of repeated exposures of PM in the lung injury is poorly documented. This study tested the hypotheses that chronic nasal instillation of residual oil fly ash (ROFA) induced not only distal lung and airway inflammation but also remodeling. In addition, we evaluated the effects of inducible nitric oxide inhibition in these responses. For this purpose, airway and lung parenchyma were evaluated by quantitative analysis of collagen and elastic fibers, immunohistochemistry for macrophages, neutrophils, inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS), and alveolar septa 8-iso prostaglandin F2 (8-iso-PGF-2) detection. Anesthetized in vivo (airway resistance, elastance, H, G, and Raw) respiratory mechanics were also analyzed. C57BL6 mice received daily 60ul of ROFA (intranasal) for five (ROFA-5d) or fifteen days (ROFA-15d). Controls have received saline (SAL). Part of the animals has received 1400W (SAL+1400W and ROFA-15d+1400W), an iNOS inhibitor, for four days before the end of the protocol. A marked neutrophil and macrophage infiltration and an increase in the iNOS, nNOS, and 8-iso-PGF2 expression was observed in peribronchiolar and alveolar wall both in ROFA-5d and in ROFA-15d groups. There was an increment of the collagen and elastic fibers in alveolar and airway walls in ROFA-15d group. The iNOS inhibition reduced all alterations induced by ROFA, except for the 8-iso-PGF2 expression. In conclusion, repeated particulate matter exposures induce extracellular matrix remodeling of airway and alveolar walls, which could contribute to the pulmonary mechanical changes observed. The mechanism involved is, at least, dependent on the inducible nitric oxide activation.
- Anacardic Acids from Cashew Nuts Ameliorate Lung Damage Induced by Exposure to Diesel Exhaust Particles in Mice(2013) CARVALHO, Ana Laura Nicoletti; ANNONI, Raquel; TORRES, Larissa Helena Lobo; DURAO, Ana Carolina Cardoso Santos; SHIMADA, Ana Lucia Borges; ALMEIDA, Francine Maria; HEBEDA, Cristina Bichels; LOPES, Fernanda Degobbi Tenorio Quirino Santos; DOLHNIKOFF, Marisa; MARTINS, Milton Arruda; SILVA, Luiz Fernando Ferraz; FARSKY, Sandra Helena Poliselli; SALDIVA, Paulo Hilario Nascimento; ULRICH, Cornelia M.; OWEN, Robert W.; MARCOURAKIS, Tania; TREVISAN, Maria Teresa Salles; MAUAD, ThaisAnacardic acids from cashew nut shell liquid, a Brazilian natural substance, have antimicrobial and antioxidant activities and modulate immune responses and angiogenesis. As inflammatory lung diseases have been correlated to environmental pollutants exposure and no reports addressing the effects of dietary supplementation with anacardic acids on lung inflammation in vivo have been evidenced, we investigated the effects of supplementation with anacardic acids in a model of diesel exhaust particle-(DEP-) induced lung inflammation. BALB/c mice received an intranasal instillation of 50 mu g of DEP for 20 days. Ten days prior to DEP instillation, animals were pretreated orally with 50, 150, or 250mg/kg of anacardic acids or vehicle (100 mu L of cashew nut oil) for 30 days. The biomarkers of inflammatory and antioxidant responses in the alveolar parenchyma, bronchoalveolar lavage fluid (BALF), and pulmonary vessels were investigated. All doses of anacardic acids ameliorated antioxidant enzyme activities and decreased vascular adhesion molecule in vessels. Animals that received 50mg/kg of anacardic acids showed decreased levels of neutrophils and tumor necrosis factor in the lungs and BALF, respectively. In summary, we demonstrated that AAs supplementation has a potential protective role on oxidative and inflammatory mechanisms in the lungs.
- Editorial: The importance of Th17/Treg imbalance in asthma and COPD development and progression(2022) LOPES, Fernanda Degobbi T. Q. S.; TIBERIO, Iolanda de Fatima Lopes Calvo; LEME, Adriana; FAIRCLOUGH, Lucy