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

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dc.contributor.authorAristoteles, Luciana R. C. R. B.
dc.contributor.authorRighetti, Renato F.
dc.contributor.authorPinheiro, Nathalia Montouro
dc.contributor.authorFranco, Rosana B.
dc.contributor.authorStarling, Claudia M.
dc.contributor.authorSilva, Julie C. P. da
dc.contributor.authorPigati, Patricia Angeli
dc.contributor.authorCaperuto, Luciana Chagas [UNIFESP]
dc.contributor.authorPrado, Carla Máximo [UNIFESP]
dc.contributor.authorDolhnikoff, Marisa
dc.contributor.authorMartins, Milton A.
dc.contributor.authorLeick, Edna A.
dc.contributor.authorTiberio, Iolanda F. L. C.
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:32:08Z
dc.date.available2016-01-24T14:32:08Z
dc.date.issued2013-08-15
dc.description.abstractBackground: 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.description.affiliationUniv São Paulo, Sch Med, Dept Clin Med, BR-01246903 São Paulo, Brazil
dc.description.affiliationUniv São Paulo, Sch Med, Dept Clin Med & Pathol, BR-01246903 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Dept Biol Sci, Diadema, SP, Brazil
dc.description.affiliationUniv São Paulo, Fac Med, BR-01246903 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Biol Sci, Diadema, SP, Brazil
dc.description.sourceWeb of Science
dc.format.extent13
dc.identifierhttp://dx.doi.org/10.1186/1471-2466-13-52
dc.identifier.citationBmc Pulmonary Medicine. London: Biomed Central Ltd, v. 13, 13 p., 2013.
dc.identifier.doi10.1186/1471-2466-13-52
dc.identifier.fileWOS000323286000001.pdf
dc.identifier.issn1471-2466
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/36650
dc.identifier.wosWOS:000323286000001
dc.language.isoeng
dc.publisherBiomed Central Ltd
dc.relation.ispartofBmc Pulmonary Medicine
dc.rightsAcesso aberto
dc.subjectLung parenchymaen
dc.subjectArginaseen
dc.subjectiNOSen
dc.subjectNitric oxideen
dc.subjectGuinea-pigen
dc.subjectnor-NOHAen
dc.subjectOxidative stressen
dc.titleModulation of the oscillatory mechanics of lung tissue and the oxidative stress response induced by arginase inhibition in a chronic allergic inflammation modelen
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