title: Recombinant human deoxyribonuclease attenuates oxidative stress in a model of eosinophilic pulmonary response in mice.
abstract: The inflammatory cells infiltrating the airways produce several mediators, such as reactive oxygen species (ROS). ROS and the oxidant-antioxidant imbalance might play an important role in the modulation of airways inflammation. In order to avoid the undesirable effects of ROS, various endogenous antioxidant strategies have evolved, incorporating both enzymatic and non-enzymatic mechanisms. Recombinant human deoxyribonuclease (rhDNase) in clinical studies demonstrated a reduction in sputum viscosity, cleaving extracellular DNA in the airways, and facilitating mucus clearance, but an antioxidant effect was not studied so far. Therefore, we evaluated whether the administration of rhDNase improves oxidative stress in a murine model of asthma. Mice were sensitized by two subcutaneous injections of ovalbumin (OVA), on days 0 and 7, followed by three lung challenges with OVA on days 14, 15, and 16. On days 15 and 16, after 2 h of the challenge with OVA, mice received 1 mg/mL of rhDNase in the lungs. Bronchoalveolar lavage fluid and lung tissue were obtained on day 17, for inflammatory and oxidative stress analysis. We showed that rhDNase did not alter the population of inflammatory cells, such as eosinophil cells, in OVA-treated rhDNase group but significantly improved oxidative stress in lung tissue, by decreasing oxygen reactive species and increasing superoxide dismutase/catalase ratio, glutathione peroxidase activity, and thiol content. Our data provide the first evidence that rhDNase decreases some measures of oxidative stress and antioxidant status in a murine model of asthma, with a potential antioxidant effect to be further studied in human asthma.
authors.affiliation: Laboratory of Pediatric Respirology, Infant Center, Institute of Biomedical Research, Pontifícia Universidade Católica do Rio Grande do Sul, 6690 Ipiranga Avenue, 2nd Floor, Room 13, Porto Alegre, RS, 90610-000, Brazil. aline.cunha@pucrs.br.
authors.forename: Aline Andrea
authors.initials: AA
authors.lastname: da Cunha
authors.affiliation: Laboratory of Pediatric Respirology, Infant Center, Institute of Biomedical Research, Pontifícia Universidade Católica do Rio Grande do Sul, 6690 Ipiranga Avenue, 2nd Floor, Room 13, Porto Alegre, RS, 90610-000, Brazil.
authors.forename: Nailê Karine
authors.initials: NK
authors.lastname: Nuñez
authors.affiliation: Laboratory of Pediatric Respirology, Infant Center, Institute of Biomedical Research, Pontifícia Universidade Católica do Rio Grande do Sul, 6690 Ipiranga Avenue, 2nd Floor, Room 13, Porto Alegre, RS, 90610-000, Brazil.
authors.forename: Rodrigo Godinho
authors.initials: RG
authors.lastname: de Souza
authors.affiliation: Laboratory of Pediatric Respirology, Infant Center, Institute of Biomedical Research, Pontifícia Universidade Católica do Rio Grande do Sul, 6690 Ipiranga Avenue, 2nd Floor, Room 13, Porto Alegre, RS, 90610-000, Brazil.
authors.forename: Mauro Henrique Moraes
authors.initials: MH
authors.lastname: Vargas
authors.affiliation: Laboratory of Pediatric Respirology, Infant Center, Institute of Biomedical Research, Pontifícia Universidade Católica do Rio Grande do Sul, 6690 Ipiranga Avenue, 2nd Floor, Room 13, Porto Alegre, RS, 90610-000, Brazil.
authors.forename: Josiane Silva
authors.initials: JS
authors.lastname: Silveira
authors.affiliation: Laboratory of Pediatric Respirology, Infant Center, Institute of Biomedical Research, Pontifícia Universidade Católica do Rio Grande do Sul, 6690 Ipiranga Avenue, 2nd Floor, Room 13, Porto Alegre, RS, 90610-000, Brazil.
authors.forename: Géssica Luana
authors.initials: GL
authors.lastname: Antunes
authors.affiliation: Laboratory of Neuroprotection and Neurometabolic Disease, Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Felipe
authors.initials: F
authors.lastname: Schmitz
authors.affiliation: Laboratory of Neuroprotection and Neurometabolic Disease, Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Angela Terezinha
authors.initials: AT
authors.lastname: de Souza Wyse
authors.affiliation: Laboratory of Respiratory Physiology, Infant Center, Institute of Biomedical Research, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Marcus Herbert
authors.initials: MH
authors.lastname: Jones
authors.affiliation: Laboratory of Pediatric Respirology, Infant Center, Institute of Biomedical Research, Pontifícia Universidade Católica do Rio Grande do Sul, 6690 Ipiranga Avenue, 2nd Floor, Room 13, Porto Alegre, RS, 90610-000, Brazil.
authors.forename: Paulo Márcio
authors.initials: PM
authors.lastname: Pitrez
mesh_terms: D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D003851:Deoxyribonucleases / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004804:Eosinophils / Q000378:metabolism*; D005260:Female; D006801:Humans; D008168:Lung / Q000276:immunology*; D051379:Mice; D010047:Ovalbumin / Q000009:adverse effects; D018384:Oxidative Stress / Q000187:drug effects*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D010047:Ovalbumin; D003851:Deoxyribonucleases
keywords: Asthma; Inflammation; Mice; Oxidative stress; rhDNase