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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Prophylactic and therapeutic treatment with the flavonone sakuranetin ameliorates LPS-induced acute lung injury

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Isabel Bittencourt-Mernak, Marcia ; 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.
Número total de Autores: 13
Tipo de documento: Artigo Científico
Fonte: AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY; v. 312, n. 2, p. L217-L230, FEB 2017.
Citações Web of Science: 11
Resumo

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. (AU)

Processo FAPESP: 14/25689-4 - Efeito do sistema colinérgico na inflamação pulmonar aguda e crônica.
Beneficiário:Carla Máximo Prado
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 08/55359-5 - Avaliação da função e da histopatologia pulmonar em modelo experimental de redução da função colinérgica em camundongos geneticamente modificados
Beneficiário:Carla Máximo Prado
Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores