Cargando…
Aerosolized Human Extracellular Superoxide Dismutase Prevents Hyperoxia-Induced Lung Injury
An important issue in critical care medicine is the identification of ways to protect the lungs from oxygen toxicity and reduce systemic oxidative stress in conditions requiring mechanical ventilation and high levels of oxygen. One way to prevent oxygen toxicity is to augment antioxidant enzyme acti...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202580/ https://www.ncbi.nlm.nih.gov/pubmed/22046389 http://dx.doi.org/10.1371/journal.pone.0026870 |
_version_ | 1782215016738455552 |
---|---|
author | Yen, Chih-Ching Lai, Yi-Wen Chen, Hsiao-Ling Lai, Cheng-Wei Lin, Chien-Yu Chen, Wei Kuan, Yu-Ping Hsu, Wu-Huei Chen, Chuan-Mu |
author_facet | Yen, Chih-Ching Lai, Yi-Wen Chen, Hsiao-Ling Lai, Cheng-Wei Lin, Chien-Yu Chen, Wei Kuan, Yu-Ping Hsu, Wu-Huei Chen, Chuan-Mu |
author_sort | Yen, Chih-Ching |
collection | PubMed |
description | An important issue in critical care medicine is the identification of ways to protect the lungs from oxygen toxicity and reduce systemic oxidative stress in conditions requiring mechanical ventilation and high levels of oxygen. One way to prevent oxygen toxicity is to augment antioxidant enzyme activity in the respiratory system. The current study investigated the ability of aerosolized extracellular superoxide dismutase (EC-SOD) to protect the lungs from hyperoxic injury. Recombinant human EC-SOD (rhEC-SOD) was produced from a synthetic cassette constructed in the methylotrophic yeast Pichia pastoris. Female CD-1 mice were exposed in hyperoxia (FiO2>95%) to induce lung injury. The therapeutic effects of EC-SOD and copper-zinc SOD (CuZn-SOD) via an aerosol delivery system for lung injury and systemic oxidative stress at 24, 48, 72 and 96 h of hyperoxia were measured by bronchoalveolar lavage, wet/dry ratio, lung histology, and 8-oxo-2′-deoxyguanosine (8-oxo-dG) in lung and liver tissues. After exposure to hyperoxia, the wet/dry weight ratio remained stable before day 2 but increased significantly after day 3. The levels of oxidative biomarker 8-oxo-dG in the lung and liver were significantly decreased on day 2 (P<0.01) but the marker in the liver increased abruptly after day 3 of hyperoxia when the mortality increased. Treatment with aerosolized rhEC-SOD increased the survival rate at day 3 under hyperoxia to 95.8%, which was significantly higher than that of the control group (57.1%), albumin treated group (33.3%), and CuZn-SOD treated group (75%). The protective effects of EC-SOD against hyperoxia were further confirmed by reduced lung edema and systemic oxidative stress. Aerosolized EC-SOD protected mice against oxygen toxicity and reduced mortality in a hyperoxic model. The results encourage the use of an aerosol therapy with EC-SOD in intensive care units to reduce oxidative injury in patients with severe hypoxemic respiratory failure, including acute respiratory distress syndrome (ARDS). |
format | Online Article Text |
id | pubmed-3202580 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-32025802011-11-01 Aerosolized Human Extracellular Superoxide Dismutase Prevents Hyperoxia-Induced Lung Injury Yen, Chih-Ching Lai, Yi-Wen Chen, Hsiao-Ling Lai, Cheng-Wei Lin, Chien-Yu Chen, Wei Kuan, Yu-Ping Hsu, Wu-Huei Chen, Chuan-Mu PLoS One Research Article An important issue in critical care medicine is the identification of ways to protect the lungs from oxygen toxicity and reduce systemic oxidative stress in conditions requiring mechanical ventilation and high levels of oxygen. One way to prevent oxygen toxicity is to augment antioxidant enzyme activity in the respiratory system. The current study investigated the ability of aerosolized extracellular superoxide dismutase (EC-SOD) to protect the lungs from hyperoxic injury. Recombinant human EC-SOD (rhEC-SOD) was produced from a synthetic cassette constructed in the methylotrophic yeast Pichia pastoris. Female CD-1 mice were exposed in hyperoxia (FiO2>95%) to induce lung injury. The therapeutic effects of EC-SOD and copper-zinc SOD (CuZn-SOD) via an aerosol delivery system for lung injury and systemic oxidative stress at 24, 48, 72 and 96 h of hyperoxia were measured by bronchoalveolar lavage, wet/dry ratio, lung histology, and 8-oxo-2′-deoxyguanosine (8-oxo-dG) in lung and liver tissues. After exposure to hyperoxia, the wet/dry weight ratio remained stable before day 2 but increased significantly after day 3. The levels of oxidative biomarker 8-oxo-dG in the lung and liver were significantly decreased on day 2 (P<0.01) but the marker in the liver increased abruptly after day 3 of hyperoxia when the mortality increased. Treatment with aerosolized rhEC-SOD increased the survival rate at day 3 under hyperoxia to 95.8%, which was significantly higher than that of the control group (57.1%), albumin treated group (33.3%), and CuZn-SOD treated group (75%). The protective effects of EC-SOD against hyperoxia were further confirmed by reduced lung edema and systemic oxidative stress. Aerosolized EC-SOD protected mice against oxygen toxicity and reduced mortality in a hyperoxic model. The results encourage the use of an aerosol therapy with EC-SOD in intensive care units to reduce oxidative injury in patients with severe hypoxemic respiratory failure, including acute respiratory distress syndrome (ARDS). Public Library of Science 2011-10-26 /pmc/articles/PMC3202580/ /pubmed/22046389 http://dx.doi.org/10.1371/journal.pone.0026870 Text en Yen et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Yen, Chih-Ching Lai, Yi-Wen Chen, Hsiao-Ling Lai, Cheng-Wei Lin, Chien-Yu Chen, Wei Kuan, Yu-Ping Hsu, Wu-Huei Chen, Chuan-Mu Aerosolized Human Extracellular Superoxide Dismutase Prevents Hyperoxia-Induced Lung Injury |
title | Aerosolized Human Extracellular Superoxide Dismutase Prevents Hyperoxia-Induced Lung Injury |
title_full | Aerosolized Human Extracellular Superoxide Dismutase Prevents Hyperoxia-Induced Lung Injury |
title_fullStr | Aerosolized Human Extracellular Superoxide Dismutase Prevents Hyperoxia-Induced Lung Injury |
title_full_unstemmed | Aerosolized Human Extracellular Superoxide Dismutase Prevents Hyperoxia-Induced Lung Injury |
title_short | Aerosolized Human Extracellular Superoxide Dismutase Prevents Hyperoxia-Induced Lung Injury |
title_sort | aerosolized human extracellular superoxide dismutase prevents hyperoxia-induced lung injury |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202580/ https://www.ncbi.nlm.nih.gov/pubmed/22046389 http://dx.doi.org/10.1371/journal.pone.0026870 |
work_keys_str_mv | AT yenchihching aerosolizedhumanextracellularsuperoxidedismutasepreventshyperoxiainducedlunginjury AT laiyiwen aerosolizedhumanextracellularsuperoxidedismutasepreventshyperoxiainducedlunginjury AT chenhsiaoling aerosolizedhumanextracellularsuperoxidedismutasepreventshyperoxiainducedlunginjury AT laichengwei aerosolizedhumanextracellularsuperoxidedismutasepreventshyperoxiainducedlunginjury AT linchienyu aerosolizedhumanextracellularsuperoxidedismutasepreventshyperoxiainducedlunginjury AT chenwei aerosolizedhumanextracellularsuperoxidedismutasepreventshyperoxiainducedlunginjury AT kuanyuping aerosolizedhumanextracellularsuperoxidedismutasepreventshyperoxiainducedlunginjury AT hsuwuhuei aerosolizedhumanextracellularsuperoxidedismutasepreventshyperoxiainducedlunginjury AT chenchuanmu aerosolizedhumanextracellularsuperoxidedismutasepreventshyperoxiainducedlunginjury |