da Cunha Aline Andrea, Nuñez Nailê Karine, de Souza Rodrigo Godinho, Vargas Mauro Henrique Moraes, Silveira Josiane Silva, Antunes Géssica Luana, Schmitz Felipe, de Souza Wyse Angela Terezinha, Jones Marcus Herbert, Pitrez Paulo Márcio
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.
Laboratory of Neuroprotection and Neurometabolic Disease, Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Mol Cell Biochem. 2016 Feb;413(1-2):47-55. doi: 10.1007/s11010-015-2638-1. Epub 2016 Jan 6.
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.
浸润气道的炎性细胞会产生多种介质，如活性氧（ROS）。ROS以及氧化还原失衡可能在气道炎症的调节中发挥重要作用。为了避免ROS的不良影响，机体进化出了各种内源性抗氧化策略，包括酶促和非酶促机制。临床研究中的重组人脱氧核糖核酸酶（rhDNase）可降低痰液黏稠度，切割气道中的细胞外DNA并促进黏液清除，但目前尚未研究其抗氧化作用。因此，我们评估了在哮喘小鼠模型中给予rhDNase是否能改善氧化应激。在第0天和第7天，通过两次皮下注射卵清蛋白（OVA）使小鼠致敏，随后在第14、15和16天对小鼠进行三次OVA肺部激发。在第15天和第16天，用OVA激发2小时后，小鼠肺内给予1mg/mL的rhDNase。在第17天获取支气管肺泡灌洗液和肺组织，用于炎症和氧化应激分析。我们发现，在OVA处理的rhDNase组中，rhDNase并未改变嗜酸性粒细胞等炎性细胞的数量，但通过降低氧活性物质并提高超氧化物歧化酶/过氧化氢酶比值、谷胱甘肽过氧化物酶活性和硫醇含量，显著改善了肺组织中的氧化应激。我们的数据首次证明，rhDNase可降低哮喘小鼠模型中的一些氧化应激指标和抗氧化状态，其潜在的抗氧化作用有待在人类哮喘中进一步研究
