NATHALIA MONTOURO PINHEIRO MENEGASSO

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LIM/20 - Laboratório de Terapêutica Experimental, Hospital das Clínicas, Faculdade de Medicina

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Autor e Coautores FMUSP-HC Normalizados: BEATRIZ MANGUEIRA SARAIVA RAMANHOLO ×

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  • conferenceObject
    Lung inflammation was attenuated by sakuranetin treatment in a model of acute lung injury
    (2014) MERNAK, Marcia; SANTANA, Fernanda; PINHEIRO, Nathalia; SARAIVA-RAMANHOLO, Beatriz; GRECCO, Simone; TIBERIO, Iolanda; MARTINS, Milton; LAGO, Joao; PRADO, Carla
  • article 42 Citação(ões) na Scopus
    Prophylactic and therapeutic treatment with the flavonone sakuranetin ameliorates LPS-induced acute lung injury
    (2017) BITTENCOURT-MERNAK, Marcia Isabel; PINHEIRO, Nathalia M.; SANTANA, Fernanda P. R.; GUERREIRO, Marina P.; SARAIVA-ROMANHOLO, Beatriz M.; GRECCO, Simone S.; CAPERUTO, Luciana C.; FELIZARDO, Raphael J. F.; CAMARA, Niels O. S.; TIBERIO, Iolanda F. L. C.; MARTINS, Mlton A.; LAGO, Joao Henrique G.; PRADO, Carla M.
    Sakuranetin is the main isolate flavonoid from Baccharis retusa (Asteraceae) leaves and exhibits anti-inflammatory and antioxidative activities. Acute respiratory distress syndrome is an acute failure of the respiratory system for which effective treatment is urgently necessary. This study investigated the preventive and therapeutic effects of sakuranetin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Animals were treated with intranasal sakuranetin 30 min before or 6 h after instillation of LPS. Twenty-four hours after ALI was induced, lung function, inflammation, macrophages population markers, collagen fiber deposition, the extent of oxidative stress, and the expression of matrix metalloprotease-9 (MMP-9), tissue inhibitor of MMP- 9 (TIMP-1) and NF-kB were evaluated. The animals began to show lung alterations 6 h after LPS instillation, and these changes persisted until 24 h after LPS administration. Preventive and therapeutic treatment with sakuranetin reduced the neutrophils in the peripheral blood and in the bronchial alveolar lavage. Sakuranetin treatment also reduced macrophage populations, particularly that of M1-like macrophages. In addition, sakurnaetin treatment reduced keratinocyte-derived chemokines (IL-8 homolog) and NF-kB levels, collagen fiber formation, MMM-9 and TIMP-1-positive cells, and oxidative stress in lung tissues compared with LPS animals treated with vehicle. Finally, sakuranetin treatment also reduced total protein, and the levels of TNF-alpha and IL-1 beta in the lung. This study shows that sakuranetin prevented and reduced pulmonary inflammation induced by LPS. Because sakuranetin modulates oxidative stress, the NF-kB pathway, and lung function, it may constitute a novel therapeutic candidate to prevent and treat ALI.
  • conferenceObject
    Essential oils reduced lung inflammation in a model of acute lung injury
    (2014) GUERREIRO, Marina; MERNAK, Marcia; SANTANA, Fernanda; PINHEIRO, Nathalia; SARAIVA-RAMANHOLO, Beatriz; CAPELLO, Tabata; TIBERIO, Iolanda; MARTINS, Milton; LAGO, Joao; PRADO, Carla
  • article 23 Citação(ões) na Scopus
    A Plant Proteinase Inhibitor from Enterolobium contortisiliquum Attenuates Pulmonary Mechanics, Inflammation and Remodeling Induced by Elastase in Mice
    (2017) THEODORO-JUNIOR, Osmar Aparecido; RIGHETTI, Renato Fraga; ALMEIDA-REIS, Rafael; MARTINS-OLIVEIRA, Bruno Tadeu; OLIVA, Leandro Vilela; PRADO, Carla Maximo; SARAIVA-ROMANHOLO, Beatriz Mangueira; LEICK, Edna Aparecida; PINHEIRO, Nathalia Montouro; LOBO, Yara Aparecida; MARTINS, Milton de Arruda; OLIVA, Maria Luiza Vilela; TIBERIO, Iolanda de Fatima Lopes Calvo
    Proteinase inhibitors have been associated with anti-inflammatory and antioxidant activities and may represent a potential therapeutic treatment for emphysema. Our aim was to evaluate the effects of a plant Kunitz proteinase inhibitor, Enterolobium contortisiliquum trypsin inhibitor (EcTI), on several aspects of experimental elastase-induced pulmonary inflammation in mice. C57/Bl6 mice were intratracheally administered elastase (ELA) or saline (SAL) and were treated intraperitoneally with EcTI (ELA-EcTI, SAL-EcTI) on days 1, 14 and 21. On day 28, pulmonary mechanics, exhaled nitric oxide (ENO) and number leucocytes in the bronchoalveolar lavage fluid (BALF) were evaluated. Subsequently, lung immunohistochemical staining was submitted to morphometry. EcTI treatment reduced responses of the mechanical respiratory system, number of cells in the BALF, and reduced tumor necrosis factor- (TNF-), matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-12 (MMP-12), tissue inhibitor of matrix metalloproteinase (TIMP-1), endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS)-positive cells and volume proportion of isoprostane, collagen and elastic fibers in the airways and alveolar walls compared with the ELA group. EcTI treatment reduced elastase induced pulmonary inflammation, remodeling, oxidative stress and mechanical alterations, suggesting that this inhibitor may be a potential therapeutic tool for chronic obstructive pulmonary disease (COPD) management.