title: Oxidative stress and nitrosative stress are involved in different stages of proteolytic pulmonary emphysema.
abstract: Our aim was to investigate the role of oxidative stress in elastase-induced pulmonary emphysema. C57BL/6 mice were subjected to pancreatic porcine elastase (PPE) instillation (0.05 or 0.5 U per mouse, i.t.) to induce pulmonary emphysema. Lungs were collected on days 7, 14, and 21 after PPE instillation. The control group was sham injected. Also, mice treated with 1% aminoguanidine (AMG) and inducible NO synthase (iNOS) knockout mice received 0.5 U PPE (i.t.), and lungs were analyzed 21 days after. We performed bronchoalveolar lavage, biochemical analyses of oxidative stress, and lung stereology and morphometry assays. Emphysema was observed histologically at 21 days after 0.5 U PPE treatment; tissues from these mice exhibited increased alveolar linear intercept and air-space volume density in comparison with the control group. TNF-α was elevated at 7 and 14 days after 0.5 U PPE treatment, concomitant with a reduction in the IL-10 levels at the same time points. Myeloperoxidase was elevated in all groups treated with 0.5 U PPE. Oxidative stress was observed during early stages of emphysema, with increased nitrite levels and malondialdehyde and superoxide dismutase activity at 7 days after 0.5 U PPE treatment. Glutathione peroxidase activity was increased in all groups treated with 0.5 U PPE. The emphysema was attenuated when iNOS was inhibited using 1% AMG and in iNOS knockout mice. Furthermore, proteolytic stimulation by PPE enhanced the expression of nitrotyrosine and iNOS, whereas the PPE+AMG group showed low expression of iNOS and nitrotyrosine. PPE stimulus also induced endothelial (e) NOS expression, whereas AMG reduced eNOS. Our results suggest that the oxidative and nitrosative stress pathways are triggered by nitric oxide production via iNOS expression in pulmonary emphysema.
authors.affiliation: Programa de Pós-graduação em Biologia Humana e Experimental, Rio de Janeiro, RJ, Brazil.
authors.forename: Manuella
authors.initials: M
authors.lastname: Lanzetti
authors.forename: Cristiane Aguiar
authors.initials: CA
authors.lastname: da Costa
authors.forename: Renata Tiscoski
authors.initials: RT
authors.lastname: Nesi
authors.forename: Marina Valente
authors.initials: MV
authors.lastname: Barroso
authors.forename: Vanessa
authors.initials: V
authors.lastname: Martins
authors.forename: Tatiana
authors.initials: T
authors.lastname: Victoni
authors.forename: Vincent
authors.initials: V
authors.lastname: Lagente
authors.forename: Karla Maria Pereira
authors.initials: KM
authors.lastname: Pires
authors.forename: Patrícia Machado Rodrigues
authors.initials: PM
authors.lastname: e Silva
authors.forename: Angela Castro
authors.initials: AC
authors.lastname: Resende
authors.forename: Luis Cristóvão
authors.initials: LC
authors.lastname: Porto
authors.forename: Cláudia Farias
authors.initials: CF
authors.lastname: Benjamim
authors.forename: Samuel Santos
authors.initials: SS
authors.lastname: Valença
mesh_terms: D000818:Animals; D005979:Glutathione Peroxidase / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology / Q000627:therapeutic use; D007962:Leukocytes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress; D010196:Pancreatic Elastase; D059748:Proteolysis; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011656:Pulmonary Emphysema / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D006146:Guanidines; D026361:Reactive Nitrogen Species; D017392:Thiobarbituric Acid Reactive Substances; C002744:3-nitrotyrosine; D014443:Tyrosine; D005979:Glutathione Peroxidase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496317:Nos2 protein, mouse; C496315:Nos3 protein, mouse; D013482:Superoxide Dismutase; D010196:Pancreatic Elastase; C004479:pimagedine