1. Oxidative stress and nitrosative stress are involved in different stages of proteolytic pulmonary emphysema
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Samuel Santos Valença, Claudia F. Benjamim, Angela Castro Resende, Renata Tiscoski Nesi, Manuella Lanzetti, Vanessa Martins, Marina Valente Barroso, Patrícia M.R. e Silva, Luís Cristóvão Porto, Tatiana Victoni, Cristiane Aguiar da Costa, Vincent Lagente, Karla Maria Pereira Pires, Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), FAPERJ, CAPES, CNPq, CAPES-COFECUB, and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
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Pathology ,MESH: Pancreatic Elastase ,Nitric Oxide Synthase Type II ,MESH: Pulmonary Disease, Chronic Obstructive ,Free radicals ,medicine.disease_cause ,Guanidines ,Biochemistry ,MESH: Tyrosine ,chemistry.chemical_compound ,MESH: Reactive Nitrogen Species ,Mice ,Pulmonary Disease, Chronic Obstructive ,0302 clinical medicine ,Elastase ,Aminoguanidine ,Leukocytes ,MESH: Thiobarbituric Acid Reactive Substances ,MESH: Animals ,MESH: Superoxide Dismutase ,0303 health sciences ,MESH: Oxidative Stress ,medicine.diagnostic_test ,biology ,Pancreatic Elastase ,Chemistry ,Nitrotyrosine ,respiratory system ,Malondialdehyde ,Reactive Nitrogen Species ,3. Good health ,MESH: Guanidines ,medicine.anatomical_structure ,Pulmonary Emphysema ,MESH: Pulmonary Emphysema ,030220 oncology & carcinogenesis ,Myeloperoxidase ,MESH: Nitric Oxide Synthase Type II ,MESH: Nitric Oxide Synthase Type III ,medicine.medical_specialty ,Nitric Oxide Synthase Type III ,MESH: Proteolysis ,Thiobarbituric Acid Reactive Substances ,Nitric oxide ,MESH: Leukocytes ,03 medical and health sciences ,MESH: Mice, Inbred C57BL ,Internal medicine ,Physiology (medical) ,medicine ,Animals ,MESH: Mice ,030304 developmental biology ,Emphysema ,Glutathione Peroxidase ,Lung ,Superoxide Dismutase ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Mice, Inbred C57BL ,Bronchoalveolar lavage ,Endocrinology ,Oxidative stress ,MESH: Glutathione Peroxidase ,Proteolysis ,biology.protein ,Tyrosine - Abstract
International audience; 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.
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