Recombinant human deoxyribonuclease attenuates oxidative stress in a model of eosinophilic pulmonary response in mice

• DOI: 10.1007/s11010-015-2638-1
• Publication Date: 2016-01-06T03:47:59Z
• Authors: Aline Andrea da C...; Nailê Karine Nuñez; Rodrigo Godinho d...; Mauro Henrique Mo...; Josiane Silva Sil...; Géssica Luana Ant...; Felipe Schmitz; Angela Terezinha ...; Marcus Herbert Jones; Paulo Márcio Pitrez
• Keywords: 0303 health sciences; Deoxyribonucleases; Ovalbumin; Asthma; Recombinant Proteins; 3. Good health; Eosinophils; Disease Models, Animal; Mice; Oxidative Stress; 03 medical and health sciences; Animals; Humans; Female; Bronchoalveolar Lavage Fluid; Lung

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.