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

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

Author Aristoteles, Luciana R. C. R. B. Google Scholar
Righetti, Renato F. Google Scholar
Pinheiro, Nathalia Montouro Google Scholar
Franco, Rosana B. Google Scholar
Starling, Claudia M. Google Scholar
Silva, Julie C. P. da Google Scholar
Pigati, Patricia Angeli Google Scholar
Caperuto, Luciana Chagas Autor UNIFESP Google Scholar
Prado, Carla Máximo Autor UNIFESP Google Scholar
Dolhnikoff, Marisa Google Scholar
Martins, Milton A. Google Scholar
Leick, Edna A. Google Scholar
Tiberio, Iolanda F. L. C. Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
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.
Keywords Lung parenchyma
Arginase
iNOS
Nitric oxide
Guinea-pig
nor-NOHA
Oxidative stress
Language English
Date 2013-08-15
Published in Bmc Pulmonary Medicine. London: Biomed Central Ltd, v. 13, 13 p., 2013.
ISSN 1471-2466 (Sherpa/Romeo, impact factor)
Publisher Biomed Central Ltd
Extent 13
Origin http://dx.doi.org/10.1186/1471-2466-13-52
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000323286000001
URI http://repositorio.unifesp.br/handle/11600/36650

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