Sakuranetin reverses vascular peribronchial and lung parenchyma remodeling in a murine model of chronic allergic pulmonary inflammation

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• 作者：Camila Pivari Pedroso Sakoda^a ; Alessandra Choqueta de Toledo^b ; Adenir Perini^b ; Nathalia Montouro Pinheiro^b ; Meire Ioshie Hiyane^d ; Simone dos Santos Grecco^c ; Iolanda de Fá ; tima Lopes Calvo Tibé ; rio^b ; Niels Olsen Saraiva Câ ; mara^d ; Milton de Arruda Martins^b ; Joã ; o Henrique Ghilardi Lago^c ; Renato Fraga Righetti^b ; ^{refragar@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Carla Má ; ximo Prado^a
• 关键词：Bronchial asthma ; Sakuranetin ; Remodeling ; Oxidative stress ; Peribronchial vessels ; Lung parenchyma
• 刊名：Acta Histochemica
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：118
• 期：6
• 页码：615-624
• 全文大小：2099 K

文摘

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 30 days and were treated with or without sakuranetin (20 mg/kg/mice) or dexamethasone (5 mg/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 and implications

Sakuranetin had anti-inflammatory and antioxidant effects, preventing vascular and distal parenchyma changes in this experimental model of asthma.