title: Sakuranetin reverses vascular peribronchial and lung parenchyma remodeling in a murine model of chronic allergic pulmonary inflammation.
abstract: OBJECTIVE
  Asthma is a disease of high prevalence and morbidity that generates high costs in hospitalization and treatment. Although the airway is involved in the physiopathology of asthma, there is also evidence of the importance of vascular and lung parenchyma inflammation and remodeling, which can contribute to the functional pulmonary alterations observed in asthmatic patients. Our aim was to evaluate treatment using sakuranetin, a flavone isolated from the twigs of Baccharis retusa (Asteraceae), on vascular and lung parenchyma alterations in an experimental murine model of asthma.
  
  
  METHODS
  Male BALB/c mice were subjected to a sensitization protocol with ovalbumin for 30days and were treated with or without sakuranetin (20mg/kg/mice) or dexamethasone (5mg/kg/mice); then, the lungs were collected for histopathological analysis. We evaluated extracellular matrix remodeling (collagen and elastic fibers), inflammation (eosinophils and NF-kB) and oxidative stress (8-isoprostane) in the pulmonary vessels and lung parenchyma. The thickness of the vascular wall was quantified, as well as the vascular endothelial growth factor (VEGF) levels.
  
  
  RESULTS
  We demonstrated that sakuranetin reduced the number of eosinophils and elastic fibers in both the pulmonary vessels and the lung parenchyma, probably due to a reduction of oxidative stress and of the transcription factor NF-kB and VEGF levels in the lung. In addition, it reduced the thickness of the pulmonary vascular wall. The treatment had no effect on the collagen fibers. In most of the parameters, the effect of sakuranetin was similar to the dexamethasone effect.
  
  
  CONCLUSIONS
  Sakuranetin had anti-inflammatory and antioxidant effects, preventing vascular and distal parenchyma changes in this experimental model of asthma.
authors.affiliation: Department of Bioscience, Federal University of Sao Paulo, Santos, SP, Brazil.
authors.forename: Camila Pivari Pedroso
authors.initials: CPP
authors.lastname: Sakoda
authors.affiliation: Department of Medicine, School of Medicine, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Alessandra Choqueta
authors.initials: AC
authors.lastname: de Toledo
authors.affiliation: Department of Medicine, School of Medicine, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Adenir
authors.initials: A
authors.lastname: Perini
authors.affiliation: Department of Medicine, School of Medicine, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Nathalia Montouro
authors.initials: NM
authors.lastname: Pinheiro
authors.affiliation: Department of Immunology, Biological Institute, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Meire Ioshie
authors.initials: MI
authors.lastname: Hiyane
authors.affiliation: Department of Bioscience Exact and Earth Science, Universidade Federal de São Paulo, Diadema, Brazil.
authors.forename: Simone Dos Santos
authors.initials: SDS
authors.lastname: Grecco
authors.affiliation: Department of Medicine, School of Medicine, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Iolanda
authors.initials: I
authors.lastname: de Fátima Lopes Calvo Tibério
authors.affiliation: Department of Immunology, Biological Institute, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Niels Olsen Saraiva
authors.initials: NOS
authors.lastname: Câmara
authors.affiliation: Department of Medicine, School of Medicine, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Milton
authors.initials: M
authors.lastname: de Arruda Martins
authors.affiliation: Department of Bioscience Exact and Earth Science, Universidade Federal de São Paulo, Diadema, Brazil.
authors.forename: João Henrique Ghilardi
authors.initials: JHG
authors.lastname: Lago
authors.affiliation: Department of Medicine, School of Medicine, Universidade de São Paulo, São Paulo, SP, Brazil. Electronic address: refragar@gmail.com.
authors.forename: Renato Fraga
authors.initials: RF
authors.lastname: Righetti
authors.affiliation: Department of Bioscience, Federal University of Sao Paulo, Santos, SP, Brazil.
authors.forename: Carla Máximo
authors.initials: CM
authors.lastname: Prado
mesh_terms: D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000473:pathology; D002908:Chronic Disease; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004804:Eosinophils / Q000187:drug effects*; D005419:Flavonoids / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000378:metabolism; D011014:Pneumonia / Q000188:drug therapy* / Q000473:pathology; D000094162:Phytoalexins
chemical_list: D003094:Collagen; D005419:Flavonoids; D010047:Ovalbumin; C099724:sakuranetin; D000094162:Phytoalexins
keywords: Bronchial asthma; Lung parenchyma; Oxidative stress; Peribronchial vessels; Remodeling; Sakuranetin