RENATO FRAGA RIGHETTI
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
- Extracellular Matrix Component Remodeling in Respiratory Diseases: What Has Been Found in Clinical and Experimental Studies?(2019) ITO, Juliana T.; LOURENCO, Juliana D.; RIGHETTI, Renato F.; TIBERIO, Iolanda F. L. C.; PRADO, Carla M.; LOPES, Fernanda D. T. Q. S.Changes in extracellular matrix (ECM) components in the lungs are associated with the progression of respiratory diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and acute respiratory distress syndrome (ARDS). Experimental and clinical studies have revealed that structural changes in ECM components occur under chronic inflammatory conditions, and these changes are associated with impaired lung function. In bronchial asthma, elastic and collagen fiber remodeling, mostly in the airway walls, is associated with an increase in mucus secretion, leading to airway hyperreactivity. In COPD, changes in collagen subtypes I and III and elastin, interfere with the mechanical properties of the lungs, and are believed to play a pivotal role in decreased lung elasticity, during emphysema progression. In ARDS, interstitial edema is often accompanied by excessive deposition of fibronectin and collagen subtypes I and III, which can lead to respiratory failure in the intensive care unit. This review uses experimental models and human studies to describe how inflammatory conditions and ECM remodeling contribute to the loss of lung function in these respiratory diseases.
- 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.
- A plant proteinase inhibitor from Enterolobium contortisiliquum attenuates airway hyperresponsiveness, inflammation and remodeling in a mouse model of asthma(2019) RODRIGUES, Adriana Palmeira Dias; BORTOLOZZO, Anelize Sartori Santos; ARANTES-COSTA, Fernanda Magalhaes; SARAIVA-ROMANHOLO, Beatriz Mangueira; SOUZA, Flavia Castro Ribas de; BRUGGEMANNI, Thayse Regina; SANTANA, Fernanda Paula Roncon; BRITO, Marlon Vilela de; BONTURI, Camila Ramalho; NUNES, Natalia Neto dos Santos; PRADO, Carla Maximo; LEICK, Edna Aparecida; OLIVA, Maria Luiza Vilela; MARTINS, Milton de Arruda; RIGHETTI, Renato Fraga; TIBERIO, Iolanda de Fatima Lopes CalvoIntroduction. Proteinase inhibitors have been associated with anti-inflammatory and antioxidant activities and may represent a potential therapeutic treatment for asthma. Purpose. The aim of the present study was to evaluate the effects of Enterolobium contortisiliquum trypsin inhibitor (EcTI) on pulmonary mechanical function, eosinophilic recruitment, inflammatory cytokines, remodeling and oxidative stress in an experimental model of chronic allergic pulmonary inflammation. Methods. BALB/c mice were divided into 4 groups: C (saline i.p and inhalations with saline), OVA (ovalbumin i.p and inhalations with ovalbumin); C+EC (saline i.p, inhalations with s aline and treatment with EcTI); OVA+EC (ovalbumin i.p, inhalations with ovalbumin and treatment with EcTI). On day 29, we performed the following tests: resistance (Rrs) and elastance (Ers) of the respiratory system; (b) quantify eosinophils, 8-ISO-PGF2 alpha, collagen and elastic fiber volume fractions; (c) IFN-gamma, IL-4, IL-5, IL-13, MMP-9, TIMP-1,TGF-beta, iNOS and p65-NF kappa B-positive cells in the airway and alveolar walls. Results. In OVA+EC group, there was an attenuation of the Rrs and Ers, reduction of eosinophils, IL-4, IL-5, IL-13, IFN-gamma, iNOS and p65-NF kappa B-positive cells compared to OVA group. The 8-ISO-PGF2 alpha, elastic and collagen fibers volume fractions as well as the positive cells for MMP-9, TIMP-1 and TGF-beta positive cells were decreased in OVA+EC compared to the OVA group. Conclusion. EcTI attenuates bronchial hyperresponsiveness, inflammation, remodeling and oxidative stress activation in this experimental mouse model of asthma.
- Inflammation and remodeling modulated by anti IL17 in model of lung injury induced by elastase in mice(2019) LEICK, Edna A.; FUKUZAKI, Silvia; RIGHETTI, Renato F.; SANTOS, Tabata M.; CAMARGO, Leandro N.; GARRIDO, Aurelio C.; ARISTOTELES, Luciana R. C. R. B.; SOUZA, Flavia C. R.; SARAIVA-ROMANHOLO, Beatriz M.; PRADO, Carla M.; MARTINS, Milton A.; TIBERIO, Iolanda F. L. C.
- Analysis of respiratory mechanics in animal models: Its use in understanding lung behavior in emphysema and asthma(2019) BISELLI, P.J.C.; KOHLER, J. Benini; RIGHETTI, R.; TIBéRIO, I. de Fátima Lopes Calvo; MARTINS, M. de Arruda; LOPES, F. Degobbi Tenorio Quirino dos SantosRespiratory mechanics assessment in animal models of respiratory diseases is considered a reliable tool to understand how structural changes impact lung function. Mathematical models, such as the equation of motion and the constant-phase model are used to describe the properties of the respiratory system. The equation of motion is valued because it is relatively simple to apply and describes the respiratory systems with few parameters. The constant-phase model is more complex but provides more detailed information about different lung compartments. In this review, we summarize how respiratory mechanics have been used to describe lung behavior as well as how these measurements reflect the progression of structural changes caused by emphysema and asthma in animal models. © 2019 Elsevier Ltd
- Bronchial vascular remodeling is attenuated by anti-IL17 in asthmatic responses exacerbated by LPS(2019) CAMARGO, Leandro; ANDRADE, Felipp Costa Pinto De; SANTOS, Tabata M.; FUKUZAKI, Silvia; PRADO, Carla Maximo; MARTINS, Milton Arruda; LEICK, Edna Aparecida; RIGHETTI, Renato Fraga; TIBERIO, Iolanda De Fatima Lopes Calvo
- Effect of anti-IL17 and/or Rho-kinase inhibitor treatments on vascular remodelling in an asthma model in mice(2019) SANTOS, Tabata M.; CAMPOS, Elaine C.; RIGUETTI, Renato F.; CAMARGO, Leandro N.; FUKUZAKI, Silvia; REZENDE, Bianca G.; SARAIVA-ROMANHOLO, Beatriz M.; PRADO, Carla M.; LEICK, Edna A.; MARTINS, Milton A.; TIBERIO, Iolanda F. L. C.
- A Guinea Pig Model of Airway Smooth Muscle Hyperreactivity Induced by Chronic Allergic Lung Inflammation: Contribution of Epithelium and Oxidative Stress(2019) VASCONCELOS, Luiz Henrique Cesar; SILVA, Maria da Conceicao Correia; COSTA, Alana Cristina; OLIVEIRA, Giuliana Amanda de; SOUZA, Iara Leao Luna de; QUEIROGA, Fernando Ramos; ARAUJO, Layanne da Cunha; CARDOSO, Glebia Alexa; RIGHETTI, Renato Fraga; SILVA, Alexandre Sergio; SILVA, Patricia Mirella da; CARVALHO, Carla Roberta de Oliveira; VIEIRA, Giciane Carvalho; TIBERIO, Iolanda de Fatima Lopes Calvo; CAVALCANTE, Fabiana de Andrade; SILVA, Bagnolia Araujo daAsthma is a heterogeneous disease of the airways characterized by chronic inflammation associated with bronchial and smooth muscle hyperresponsiveness. Currently, different murine models for the study of asthma show poor bronchial hyperresponsiveness due to a scarcity of smooth muscle and large airways, resulting in a failure to reproduce smooth muscle hyperreactivity. Thus, we aimed to standardize a guinea pig model of chronic allergic lung inflammation mimicking airway smooth muscle hyperreactivity observed in asthmatics (Asth). Animals were randomly divided into a control group (Ctrl), which received saline (0.9% NaCl), and the Asth group, subjected to in vivo sensitization with ovalbumin (OVA) nebulization. Morphological analysis was performed by hematoxylin-eosin staining. Bronchial hyperresponsiveness was evaluated by nebulization time in the fifth, sixth, and seventh inhalations (NT5-7) and tracheal isometric contractions were assessed by force transducer. Total antioxidant capacity was measured by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method and protein expression by Western blot. Histologically, the Asth group developed peribronchial cellular infiltrate, epithelial hyperplasia and smooth muscle thickening. After the fourth nebulization, the Asth group developed bronchial hyperreactivity. The trachea from the Asth group contracted after in vitro stimulation with OVA, differing from the Ctrl group, which showed no response. Additionally, airway smooth muscle hyperreactivity to carbachol and histamine was observed in the Asth group only in intact epithelium preparations, but not to KCl, and this effect was associated with an augmented production of reactive oxygen species. Moreover, lung inflammation impaired the relaxant potency of isoproterenol only in intact epithelium preparations, without interfering with nifedipine, and it was found to be produced by transforming growth factor-beta negative modulation of beta adrenergic receptors and, furthermore, big-conductance Ca2+-sensitive K+ channels. These effects were also associated with increased levels of phosphatidylinositol 3-kinases but not extracellular signal-regulated kinases 1/2 or phosphorylation, and augmented alpha-actin content as well, explaining the increased smooth muscle mass. Furthermore, pulmonary antioxidant capacity was impaired in the Asth group. Therefore, we developed a standardized and easy-touse, reproducible guinea pig model of lung inflammation that mimics airway smooth muscle hypercontractility, facilitating the investigation of the mechanisms of bronchial hyperresponsiveness in asthma and new therapeutic alternatives.