CARLA MAXIMO PRADO
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
16 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 16
- Effects of environmental exposure to iron powder in an elastase mice model(2022) GALLI, T. Tafarel; CAMPOS, E. C.; SANTOS, T. M.; FUKUZAKI, S.; CAMARGO, L. N.; BEZERRA, S. K. M.; HAMAGUCHI, S. S. S.; SILVA, F. J. A. Da; SARAIVA-ROMANHOLO, B. M.; OLIVO, C. R.; PRADO, C. M.; LOPES, F. Degobbi Tenorio Quirino Dos Santos; LEICK, E. A.; BOUROTTE, C. L. M.; BENSENOR, I. J. M.; LOTUFO, P. A.; RIGHETTI, R. F.; TIBERIO, I. F. L. C.
- Effect of Anti-IL17 Antibody Treatment Alone and in Combination With Rho-Kinase Inhibitor in a Murine Model of Asthma(2018) SANTOS, Tabata M. dos; RIGHETTI, Renato F.; CAMARGO, Leandro do N.; SARAIVA-ROMANHOLO, Beatriz M.; ARISTOTELES, Luciana R. C. R. B.; SOUZA, Flavia C. R. de; FUKUZAKI, Silvia; ALONSO-VALE, Maria I. C.; CRUZ, Maysa M.; PRADO, Carla M.; LEICK, Edna A.; MARTINS, Milton A.; TIBERIO, Iolanda F. L. C.Background: Interleukin-17 (IL-17) and Rho-kinase (ROCK) play an important role in regulating the expression of inflammatory mediators, immune cell recruitment, hyper-responsiveness, tissue remodeling, and oxidative stress. Modulation of IL-17 and ROCK proteins may represent a promising approach for the treatment of this disease. Objective: To study the effects of an anti-IL17 neutralizing antibody and ROCK inhibitor treatments, separately and in combination, in a murine model of chronic allergy-induced lung inflammation. Methods: Sixty-four BALBc mice, were divided into eight groups (n = 8): SAL (saline-instilled); OVA (exposed-ovalbumin); SAL-RHOi (saline and ROCK inhibitor), OVA-RHOi (exposed-ovalbumin and ROCK inhibitor); SAL-anti-IL17 (saline and anti-IL17); OVA-anti-IL1 7 (exposed-ovalbumin and anti-IL1 7); SAL-RHOi-anti-IL17 (saline, ROCK inhibitor and anti-IL17); and OVA-RHOi-anti-IL17 (exposed-ovalbumin, anti-IL17, and ROCK inhibitor). A 28-day protocol of albumin treatment was used for sensitization and induction of pulmonary inflammation. The anti-IL17A neutralizing antibody (7.5 mu g per treatment) was administered by intraperitoneal injection and ROCK inhibitor (Y-27632) intranasally (10 mg/kg), 1 h prior to each ovalbumin challenge (days 22, 24, 26, and 28). Results: Treatment with the anti-IL17 neutralizing antibody and ROCK inhibitor attenuated the percentage of maximal increase of respiratory system resistance and respiratory system elastance after challenge with methacholine and the inflammatory response markers evaluated (CD4(+), CD8(+), ROCK1, ROCK2, IL-4, IL-5, IL-6, IL-10 IL-13, IL-17, TNF-alpha, TGF-beta, NF-kappa B, dendritic cells, iNOS, MMP-9, MMP-12, TIMP-1, FOXP3, isoprostane, biglycan, decorin, fibronectin, collagen fibers content and gene expression of IL-17, VAChT, and arginase) compared to the OVA group (p < 0.05). Treatment with anti-IL17 and the ROCK inhibitor together resulted in potentiation in decreasing the percentage of resistance increase after challenge with methacholine, decreased the number of IL-5 positive cells in the airway, and reduced, IL-5, TGF beta, FOXP3, ROCK1 and ROCK2 positive cells in the alveolar septa compared to the OVA-RHOi and OVA-anti-IL17 groups (p < 0.05). Conclusion: Anti-IL17 treatment alone or in conjunction with the ROCK inhibitor, modulates airway responsiveness, inflammation, tissue remodeling, and oxidative stress in mice with chronic allergic lung inflammation.
conferenceObject Effects Of Chronic Treatment With Cape, A Specific Nf Kappa-B Inhibitor, Compared To Rho Quinase Inhibitor Or Corticosteroid On Airway Hyperresponsiveness In Mice With Chronic Allergic Pulmonary Inflammation(2016) TIBERIO, I. F.; SOUZA, F. C. R.; SANTOS, T. M.; ARISTOTELES, L. R.; RIGHETTI, R. F.; SARAIVA-ROMANHOLO, B.; PRADO, C. M.; COSTA, F. M. A.; LEICK, E. A.; MARTINS, M. A.- 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.
- Y-27632 is associated with corticosteroid-potentiated control of pulmonary remodeling and inflammation in guinea pigs with chronic allergic inflammation(2015) PIGATI, Patricia Angeli; RIGHETTI, Renato Fraga; POSSA, Samantha Souza; ROMANHOLO, Beatriz Saraiva; RODRIGUES, Adriana Palmeira Dias; SANTOS, Anelize Sartori Alves dos; XISTO, Debora Gonalves; ANTUNES, Mariana Alves; PRADO, Carla Maximo; LEICK, Edna Aparecida; MARTINS, Milton de Arruda; ROCCO, Patrcia Rieken Macedo; TIBERIO, Iolanda de Fatima Lopes CalvoBackground: Previously, we showed that treatment with the Rho-kinase inhibitor Y-27632 was able to control airway responsiveness, inflammation, remodeling, and oxidative stress in an animal model of asthma, suggesting that this drug is beneficial in asthma. However, studies evaluating the effects of these inhibitors in conjunction with corticosteroids on chronic pulmonary inflammation have not been conducted. Therefore, we evaluated the effects of treatment with the Rho-kinase inhibitor Y-27632, with or without concurrent dexamethasone treatment, on airway and lung tissue mechanical responses, inflammation, extracellular matrix remodeling, and oxidative stress in guinea pigs with chronic allergic inflammation. Methods: The guinea pigs were subjected to seven ovalbumin or saline inhalation exposures. Treatment with Y-27632 (1 mM) and dexamethasone (2 mg/kg) started at the fifth inhalation. Seventy-two hours after the seventh inhalation, the pulmonary mechanics were evaluated and exhaled nitric oxide (E-NO) levels were determined. The lungs were removed and histological analysis was performed using morphometry. Results: The treatment of guinea pigs with the Rho-kinase inhibitor and dexamethasone (ORC group) decreased ENO, the maximal mechanical responses after antigen challenge, inflammation, extracellular matrix remodeling and oxidative stress in the lungs. This therapeutic strategy reduced the levels of collagen and IFN-gamma in the airway walls, as well as IL-2, IFN-gamma, 8-iso-PGF2 alpha and NF-kappa B in the distal parenchyma, when compared to isolated treatment with corticosteroid or Rho-kinase inhibitor (P < 0.05) and reduced the number of TIMP-1-positive cells and eosinophils in the alveolar septa compared to corticosteroid-treated animals (P < 0.05). The combined treatment with the Rho-kinase inhibitor and the corticosteroid provided maximal control over the remodeling response and inflammation in the airways and parenchyma. Conclusions: Rho-kinase inhibition, alone or in combination with corticosteroids, can be considered a future pharmacological tool for the control of asthma.
- Inducible Nitric Oxide Synthase Inhibition Attenuates Physical Stress-Induced Lung Hyper-Responsiveness and Oxidative Stress in Animals with Lung Inflammation(2012) MARQUES, Ricardo Henrique; REIS, Fabiana G.; STARLING, Claudia M.; CABIDO, Claudia; ALMEIDA-REIS, Rafael de; DOHLNIKOFF, Marisa; PRADO, Carla M.; LEICK, Edna A.; MARTINS, Milton A.; TIBERIO, Iolanda F. L. C.Mechanisms involved in stress-induced asthmatic alterations have been poorly characterised. We assessed whether inducible nitric oxide synthase (iNOS) inhibition modulates the stress-amplified lung parenchyma responsiveness, oxidative stress and extracellular matrix remodelling that was previously increased by chronic lung inflammation. Guinea pigs were subjected to 7 exposures to ovalbumin (1-5 mg/ml) or saline (OVA and SAL groups) over 4 weeks. To induce behavioural stress, animals were subjected to a forced swimming protocol (5 times/week, over 2 weeks; SAL-Stress and OVA-Stress groups) 24 h after the 4th inhalation. 1400W (iNOS-specific inhibitor) was administered intraperitoneally in the last 4 days of the protocol (SAL-1400W, OVA-1400W, SAL-Stress+1400W and OVA-Stress+1400W groups). Seventy-two hours after the last inhalation, animals were anaesthetised and exsanguinated, and adrenal glands were removed. Lung tissue resistance and elastance were evaluated by oscillatory mechanics and submitted for histopathological evaluation. Stressed animals had higher adrenal weights compared to non-stressed groups, which were reduced by 1400W treatment. Behavioural stress in sensitised animals amplified the resistance and elastance responses after antigen challenge, numbers of eosinophils and iNOS+ cells, actin content and 8-iso-PGF2 alpha density in the distal lung compared to the OVA group. 1400W treatment in ovalbumin-exposed and stressed animals reduced lung mechanics, iNOS+ cell numbers and 8-iso-PGF2a density compared to sensitised and stressed animals that received vehicle treatment. We concluded that stress amplifies the distal lung constriction, eosinophilic inflammation, iNOS expression, actin content and oxidative stress previously induced by chronic lung inflammation. iNOS-derived NO contributes to stress-augmented lung tissue functional alterations in this animal model and is at least partially due to activation of the oxidative stress pathway.
- Preventive and therapeutic effect of anti-IL-17 in an experimental model of elastase-induced lung injury in C57Bl6 mice(2021) FUKUZAKI, Silvia; RIGHETTI, Renato Fraga; SANTOS, Tabata Maruyama dos; CAMARGO, Leandro do Nascimento; ARISTOTELES, Luciana R. C. R. B.; SOUZA, Flavia C. R.; GARRIDO, Aurelio C.; SARAIVA-ROMANHOLO, Beatriz Mangueira; LEICK, Edna Aparecida; PRADO, Carla Maximo; MARTINS, Milton de Arruda; TIBERIO, Iolanda de Fatima Lopes CalvoChronic obstructive pulmonary disease (COPD) is an important health care issue, and IL-17 can modulate inflammatory responses. We evaluated preventive and therapeutic effect of anti-interleukin (IL)-17 in a model of lung injury induced by elastase, using 32 male C57Bl6 mice, divided into 4 groups: SAL, ELASTASE CONTROL (EC), ELASTASE I PREVENTIVE ANTI-IL-17 (EP), and ELASTASE + THERAPEUTIC ANTI-IL-17 (ET). On the 29th day, animals were anesthetized with thiopental, tracheotomized, and placed on a ventilator to evaluate lung mechanical, exhaled nitric oxide (eNO), and total cells of bronchoalveolar lavage fluid was collected. We performed histological techniques, and linear mean intercept (Lm) was analyzed. Both treatments with anti-IL-17 decreased respiratory resistance and elastance, airway resistance, elastance of pulmonary parenchyma, eNO, and Lm compared with EC. There was reduction in total cells and macrophages in ET compared with EC. Both treatments decreased nuclear factor-kappa B, inducible nitric oxide synthase, matrix metalloproteinase (MMP)-9, MMP-12, transforming growth factor-beta, tumor necrosis factor-alpha, neutrophils, IL-1 beta, isoprostane, and IL-17 in airways and alveolar septa; collagen fibers, decorin and lumican in airways; and elastic fibers and fibronectin in alveolar septa compared with EC. There was reduction of collagen fibers in alveolar septa and biglycan in airways in EP and a reduction of eNO synthase in airways in ET. In conclusion, both treatments with anti-IL-17 contributed to improve most of parameters evaluated in inflammation and extracellular matrix remodeling in this model of lung injury.
- Specific NFKappaB and Rho-Quinase inhibitors compared to corticosteroid in asthma model in mice(2017) SOUZA, Flavia; CAMARGO, Leandro; RIGHETTI, Renato; ARISTOTELES, Luciana; MARUYAMA, Tabata; FUKUZAKI, Silvia; LEICK, Edna; MARTINS, Milton; PRADO, Carla; TIBERIO, Iolanda; ROMANHOLO, Beatriz
- Effects of anti-IL17 on acute lung injury induced by LPS in mice(2017) RIGHETTI, Renato; SANTOS, Tabata Maruyama dos; CAMARGO, Leandro do Nascimento; ARISTOTELES, Luciana Ritha de Cassia Rolim Barbosa; FUKUZAKI, Silvia; SOUZA, Flavia Castro Ribas de; CRUZ, Maysa Mariana; ALONSO-VALE, Maria Isabel Cardoso; SARAIVA-ROMANHOLO, Beatriz Mangueira; LEICK, Edna Aparecida; MARTINS, Milton de Arruda; PRADO, Carla Maximo; TIBERIO, Iolanda de Fatima Lopes Calvo
- Glycine efficacy for prevention or treatment on LPS-acute lung injury in mice(2021) RIGHETTI, Renato Fraga; GOTO, Bryan Shinji Haneda; SANTOS, Tabata Maruyama Dos; CAMARGO, Leandro Do Nascimento; SARAIVA-ROMANHOLO, Beatriz Mangueira; BEZERRA, Suellen Karoline Moreira; LEICK, Edna Aparecida; PRADO, Carla Maximo; MARTINS, Milton De Arruda; NOGUEIRA, Ruben Siedlarczyk; CARVALHO NETO, Jose Carlos Sa De; SOUZA, Daniel Alexandre De; SALU, Bruno Ramos; OLIVA, Maria Luiza Vilela; TIBERIO, Iolanda De Fatima Lopes Calvo