RENATO FRAGA RIGHETTI
Projetos de Pesquisa
Unidades Organizacionais
LIM/20 - Laboratório de Terapêutica Experimental, Hospital das Clínicas, Faculdade de Medicina
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
- Virgin Coconut Oil Supplementation Prevents Airway Hyperreactivity of Guinea Pigs with Chronic Allergic Lung Inflammation by Antioxidant Mechanism(2020) VASCONCELOS, Luiz Henrique C.; SILVA, Maria da Conceicao C.; COSTA, Alana C.; OLIVEIRA, Giuliana A. de; SOUZA, Iara Leao Luna de; RIGHETTI, Renato F.; QUEIROGA, Fernando R.; CARDOSO, Glebia A.; SILVA, Alexandre S.; SILVA, Patricia M. da; VIEIRA, Giciane C.; TIBERIO, Iolanda de F. L. C.; MADRUGA, Marta S.; CAVALCANTE, Fabiana de A.; SILVA, Bagnolia A. daAsthma is a chronic inflammatory disease of the airways characterized by immune cell infiltrates, bronchial hyperresponsiveness, and declining lung function. Thus, the possible effects of virgin coconut oil on a chronic allergic lung inflammation model were evaluated. Morphology of lung and airway tissue exhibited peribronchial inflammatory infiltrate, epithelial hyperplasia, and smooth muscle thickening in guinea pigs submitted to ovalbumin sensitization, which were prevented by virgin coconut oil supplementation. Additionally, in animals with lung inflammation, trachea contracted in response to ovalbumin administration, showed a greater contractile response to carbachol (CCh) and histamine, and these responses were prevented by the virgin coconut oil supplementation. Apocynin, a NADPH oxidase inhibitor, did not reduce the potency of CCh, whereas tempol, a superoxide dismutase mimetic, reduced potency only in nonsensitized animals. Catalase reduced the CCh potency in nonsensitized animals and animals sensitized and treated with coconut oil, indicating the participation of superoxide anion and hydrogen peroxide in the hypercontractility, which was prevented by virgin coconut oil. In the presence of L-NAME, a nitric oxide synthase (NOS) inhibitor, the CCh curve remained unchanged in nonsensitized animals but had increased efficacy and potency in sensitized animals, indicating an inhibition of endothelial NOS but ineffective in inhibiting inducible NOS. In animals sensitized and treated with coconut oil, the CCh curve was not altered, indicating a reduction in the release of NO by inducible NOS. These data were confirmed by peribronchiolar expression analysis of iNOS. The antioxidant capacity was reduced in the lungs of animals with chronic allergic lung inflammation, which was reversed by the coconut oil, and confirmed by analysis of peribronchiolar 8-iso-PGF2 alpha content. Therefore, the virgin coconut oil supplementation reverses peribronchial inflammatory infiltrate, epithelial hyperplasia, smooth muscle thickening, and hypercontractility through oxidative stress and its interactions with the NO pathway.
- Treatment with proteinase inhibitor from Enterolobium contortisiliquum in mice with asthma-COPD(2020) BARBOSA, Jessica Anastacia Silva; SILVA, Luana Laura Sales Da; JOAO, Juliana Morelli Lopes Goncalves; SANTOS, Tabata Maruyama Dos; CAMARGO, Leandro Nascimento; CAMPOS, Elaine Cristina De; GALLI, Thiago Tafarel; SARAIVA-ROMANHOLO, Beatriz Mangueira; BEZERRA, Suellen Karoline Moreira; HAMAGUCHI, Sara Sumie Sobral; LEICK, Edna Aparecida; PRADO, Carla Maximo; MARTINS, Milton De Arruda; OLIVO, Maria Luiza Vilela; RIGHETTI, Renato Fraga; TIBERIO, Iolanda De Fatima Lopes Calvo
- Bronchial Vascular Remodeling Is Attenuated by Anti-IL-17 in Asthmatic Responses Exacerbated by LPS(2020) CAMARGO, Leandro do Nascimento; SANTOS, Tabata Maruyama dos; ANDRADE, Felipp Costa Pinto de; FUKUZAKI, Silvia; LOPES, Fernanda Degobbi Tenorio Quirino dos Santos; MARTINS, Milton de Arruda; PRADO, Carla Maximo; LEICK, Edna Aparecida; RIGHETTI, Renato Fraga; TIBERIO, Iolanda de Fatima Lopes CalvoIntroduction Although the major alterations associated with asthma are related to the airways, there is also evidence of the importance of peribronchial vascular inflammation and remodeling in its pathophysiology. Objectives To determine the effects of anti-IL-17 therapy on peribronchial vessels of an asthma model exacerbated by lipopolysaccharide. Methods We evaluated several factors, including lung function, inflammation, oxidative stress, vascular remodeling, and signaling pathways present in the peribronchial vessels of 66 male BALB/c mice exposed to ovalbumin and treated (or not) treated with anti-IL-17. Twenty-four hours before the end of the experimental protocol, groups of sensitized animals (OVA-LPS and OVA-LPS anti-IL-17) also received LPS. Results The OVA-LPS-anti-IL-17 group presented a decrease in several factors [airway resistance and elastance, bronchoalveolar lavage fluid (BALF) cell counts, inflammatory response, eosinophils, TSLP, IL-33, TARC, TNF-alpha, CD4+, CD8+, IL-4, IL-6, IL-10, IL-17, and VEGF positive cells/10(4)mu m(2), peribronchovascular edema, and angiogenesis], including remodeling (MMP-9, MMP-12, TIMP-1 and TGF-beta positive cells and volume fraction of collagen fibers I, collagen fibers III, collagen fibers V, decorin, lumican, actin, biglycan, fibronectin, and integrin), oxidative stress (iNOS positive cells and volume fraction of PGF2 alpha), and signaling pathways (FoxP3), as well as dendritic cells, NF-kB, ROCK-1, ROCK-2, STAT-1, and phosphor-STAT1-positive cells compared to OVA-LPS (p < 0.05). Conclusions In this model of LPS-induced asthma exacerbation, IL-17 inhibition represents a promising therapeutic strategy, indicating the potential of bronchial vascular control of Th2 and Th17 responses and the activation of the remodeling and oxidative stress pathways, associated with the control of signaling pathways.
- Plant protease inhibitors compared to corticosteroids in mice with Asthma-COPD(2020) JOAO, Juliana Morelli Lopes Goncalves; BARBOSA, Jessica Anastacia Silva; SILVA, Luana Laura Sales Da; SANTOS, Tabata Maruyama Dos; CAMARGO, Leandr Do Nascimento; CAMPOS, Elaine Cristina De; GALIL, Thiago Tafarel; SARAIVA-ROMANHOLO, Beatriz Mangueira; BEZERRA, Suellen Karoline Moreira; HAMAGUCHI, Sara Sumie Sobral; MARTINS, Milton De Arruda; OLIVO, Maria Luiza Vilela; RIGHETTI, Renato Fraga; TIBERIO, Iolanda De Fatima Lopes Calvo; LEICK, Edna Aparecida
- Effects of Bauhinia bauhinioides kallikrein proteinase inhibitor in mice with asthma-COPD(2020) SILVA, Luana Laura Sales da; BARBOSA, Jessica Anastacia Silva; JOAO, Juliana Morelli Lopes Goncalves; SANTOS, Tabata Maruyama Dos; CAMARGO, Leandro Do Nascimento; CAMPOS, Elaine Cristina De; GALLI, Thiago Tafarel; SARAIVA-ROMANHOLO, Beatriz Mangueira; BEZERRA, Suellen Karoline Moreira; HAMAGUCHI, Sara Sumie Sobral; LEICK, Edna Aparecida; PRADO, Carla Maximo; MARTINS, Milton De Arruda; OLIVO, Maria Luiza Vilela; RIGHETTI, Renato Fraga; TIBERIO, Iolanda De Fatima Lopes Calvo
- Effect of anti-IL17 and/or Rho-kinase inhibitor treatments on vascular remodeling induced by chronic allergic pulmonary inflammation(2020) SANTOS, Tabata M. dos; RIGHETTI, Renato F.; REZENDE, Bianca G.; CAMPOS, Elaine C.; CAMARGO, Leandro do N.; SARAIVA-ROMANHOLO, Beatriz M.; FUKUZAKI, Silvia; PRADO, Carla M.; LEICK, Edna A.; MARTINS, Milton A.; TIBERIO, Iolanda F. L. C.Background and aims: Expansion and morphological dysregulation of the bronchial vascular network occurs in asthmatic airways. Interleukin (IL) -17 and Rho-kinase (ROCK) are known to act in inflammation control and remodeling. Modulation of Rho-kinase proteins and IL-17 may be a promising approach for the treatment of asthma through the control of angiogenesis. Our objective was to analyze the effects of treatment with anti-IL17 and/or Rho-kinase inhibitor on vascular changes in mice with chronic allergic pulmonary inflammation. Methods: Sixty-four BALB/c mice, with pulmonary inflammation induced by ovalbumin were treated with anti-IL17A (7.5/mu g per dose, intraperitoneal) and/or Rho-kinase inhibitor (Y-27632-10 mg/kg, intranasal), 1 h before each ovalbumin challenge (22, 24, 26, and 28/days). Control animals were made to inhale saline. At the end of the protocol, lungs were removed, and morphometric analysis was performed to quantify vascular inflammatory, remodeling, and oxidative stress responses. Results: Anti-IL17 or Rho-kinase inhibitor reduced the number of CD4(+), CD8(+), dendritic cells, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, Rho-kinase 1 and 2, transforming growth factor (TGF-beta), vascular endothelial growth factor (VEGF), nuclear factor (NF)-KappaB, iNOS, metalloproteinase (MMP)-9, MMP-12, metalloproteinase inhibitor-1 (TIMP-1), FOXP-3, signal transducer and activator of transcription 1 (STAT1) and phospho-STAT1-positive cells, and actin, endothelin-1, isoprostane, biglycan, decorin, fibronectin and the collagen fibers volume fraction compared with the ovalbumin group (p < 0.05). The combination treatment, when compared with anti-IL17, resulted in potentiation of decrease in the number of IL1 beta- and dendritic cells-positive cells. When we compared the OVA-RHO inhibitor-anti-IL17 with OVA-RHO inhibitor we found a reduction in the number of CD8(+) and IL-17, TGF-beta, and phospho-STAT1-positive cells and endothelin-1 in the vessels (p < 0.05). There was an attenuation in the number of ROCK 2-positive cells in the group with the combined treatment when compared with anti-IL17 or Rho-kinase inhibitor-treated groups (p < 0.05). Conclusion: We observed no difference in angiogenesis after treatment with Rho-kinase inhibitor and anti-IL17. Although the treatments did not show differences in angiogenesis, they showed differences in the markers involved in the angiogenesis process contributing to inflammation control and vascular remodeling. The reviews of this paper are available via the supplemental material section.