Modulation of the oscillatory mechanics of lung tissue and the oxidative stress response induced by arginase inhibition in a chronic allergic inflammation model

Show simple item record

dc.contributor.author Aristoteles, Luciana R. C. R. B.
dc.contributor.author Righetti, Renato F.
dc.contributor.author Pinheiro, Nathalia Montouro
dc.contributor.author Franco, Rosana B.
dc.contributor.author Starling, Claudia M.
dc.contributor.author Silva, Julie C. P. da
dc.contributor.author Pigati, Patricia Angeli
dc.contributor.author Caperuto, Luciana Chagas [UNIFESP]
dc.contributor.author Prado, Carla Máximo [UNIFESP]
dc.contributor.author Dolhnikoff, Marisa
dc.contributor.author Martins, Milton A.
dc.contributor.author Leick, Edna A.
dc.contributor.author Tiberio, Iolanda F. L. C.
dc.date.accessioned 2016-01-24T14:32:08Z
dc.date.available 2016-01-24T14:32:08Z
dc.date.issued 2013-08-15
dc.identifier http://dx.doi.org/10.1186/1471-2466-13-52
dc.identifier.citation Bmc Pulmonary Medicine. London: Biomed Central Ltd, v. 13, 13 p., 2013.
dc.identifier.issn 1471-2466
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/36650
dc.description.abstract Background: the importance of the lung parenchyma in the pathophysiology of asthma has previously been demonstrated. Considering that nitric oxide synthases (NOS) and arginases compete for the same substrate, it is worthwhile to elucidate the effects of complex NOS-arginase dysfunction in the pathophysiology of asthma, particularly, related to distal lung tissue. We evaluated the effects of arginase and iNOS inhibition on distal lung mechanics and oxidative stress pathway activation in a model of chronic pulmonary allergic inflammation in guinea pigs.Methods: Guinea pigs were exposed to repeated ovalbumin inhalations (twice a week for 4 weeks). the animals received 1400 W (an iNOS-specific inhibitor) for 4 days beginning at the last inhalation. Afterwards, the animals were anesthetized and exsanguinated; then, a slice of the distal lung was evaluated by oscillatory mechanics, and an arginase inhibitor (nor-NOHA) or vehicle was infused in a Krebs solution bath. Tissue resistance (Rt) and elastance (Et) were assessed before and after ovalbumin challenge (0.1%), and lung strips were submitted to histopathological studies.Results: Ovalbumin-exposed animals presented an increase in the maximal Rt and Et responses after antigen challenge (p<0.001), in the number of iNOS positive cells (p<0.001) and in the expression of arginase 2, 8-isoprostane and NF-kB (p<0.001) in distal lung tissue. the 1400 W administration reduced all these responses (p<0.001) in alveolar septa. Ovalbumin-exposed animals that received nor-NOHA had a reduction of Rt, Et after antigen challenge, iNOS positive cells and 8-isoprostane and NF-kB (p<0.001) in lung tissue. the activity of arginase 2 was reduced only in the groups treated with nor-NOHA (p <0.05). There was a reduction of 8-isoprostane expression in OVA-NOR-W compared to OVA-NOR (p<0.001).Conclusions: in this experimental model, increased arginase content and iNOS-positive cells were associated with the constriction of distal lung parenchyma. This functional alteration may be due to a high expression of 8-isoprostane, which had a procontractile effect. the mechanism involved in this response is likely related to the modulation of NF-kB expression, which contributed to the activation of the arginase and iNOS pathways. the association of both inhibitors potentiated the reduction of 8-isoprostane expression in this animal model. en
dc.format.extent 13
dc.language.iso eng
dc.publisher Biomed Central Ltd
dc.relation.ispartof Bmc Pulmonary Medicine
dc.rights Acesso aberto
dc.subject Lung parenchyma en
dc.subject Arginase en
dc.subject iNOS en
dc.subject Nitric oxide en
dc.subject Guinea-pig en
dc.subject nor-NOHA en
dc.subject Oxidative stress en
dc.title Modulation of the oscillatory mechanics of lung tissue and the oxidative stress response induced by arginase inhibition in a chronic allergic inflammation model en
dc.type Artigo
dc.contributor.institution Universidade de São Paulo (USP)
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.description.affiliation Univ São Paulo, Sch Med, Dept Clin Med, BR-01246903 São Paulo, Brazil
dc.description.affiliation Univ São Paulo, Sch Med, Dept Clin Med & Pathol, BR-01246903 São Paulo, Brazil
dc.description.affiliation Universidade Federal de São Paulo, Dept Biol Sci, Diadema, SP, Brazil
dc.description.affiliation Univ São Paulo, Fac Med, BR-01246903 São Paulo, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Biol Sci, Diadema, SP, Brazil
dc.identifier.file WOS000323286000001.pdf
dc.identifier.doi 10.1186/1471-2466-13-52
dc.description.source Web of Science
dc.identifier.wos WOS:000323286000001



File

Name: WOS000323286000001.pdf
Size: 1.612Mb
Format: PDF
Description:
Open file

This item appears in the following Collection(s)

Show simple item record

Search


Browse

Statistics

My Account