Evaluation of Lecithinized Superoxide Dismutase for the Prevention of Acute Respiratory Distress Syndrome in Animal Models.
For acute respiratory distress syndrome (ARDS), mechanical ventilation (MV) is a life-saving intervention without alternative; however, MV can cause ventilator-induced lung injury. Reactive oxygen species (ROS) play important roles in the pathogenesis of both ARDS and ventilator-induced lung injury. Lecithinized superoxide dismutase (PC-SOD) overcomes the limitations of superoxide dismutase such as low tissue affinity and low stability in plasma. In this study, we examined the effect of PC-SOD on tissue injury, edema, and inflammation in the lung and other organs of mice subjected to cecal ligation and puncture (CLP), LPS administration, or MV. The severity of the lung injury was assessed on the basis of vascular permeability, histopathologic evaluation, and lung mechanics. Intravenous PC-SOD administration (the first administered just before CLP) increased the survival rate and decreased vascular permeability in mice subjected to CLP. PC-SOD, but not dexamethasone or sivelestat sodium hydrate (sivelestat), suppressed CLP-induced kidney injury and systemic inflammation. PC-SOD also suppressed vascular permeability, tissue injury, and inflammation in the lung induced by LPS administration. Moreover, PC-SOD, but not dexamethasone or sivelestat, suppressed vascular permeability, edema, tissue injury, and mechanical alterations in the lung induced by MV. In vivo imaging analysis of ROS revealed that CLP, LPS administration, and MV increased the level of ROS and that this increase was suppressed by PC-SOD. The results of this study thus suggest that, on the basis of its ROS-reducing properties, intravenous administration of PC-SOD may be beneficial for patients at high risk of developing ARDS.
1 Laboratory of Bio-Analytical Chemistry, Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo, Japan.
Ken-Ichiro
KI
Tanaka
1 Laboratory of Bio-Analytical Chemistry, Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo, Japan.
Fumiya
F
Tamura
2 Department of System Chemotherapy and Molecular Sciences, Division of Bioinformatics and Chemical Genomics, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
Toshifumi
T
Sugizaki
1 Laboratory of Bio-Analytical Chemistry, Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo, Japan.
Masahiro
M
Kawahara
3 Departments of Biochemistry and Metabolic Science and.
Keiji
K
Kuba
4 Biological Informatics and Experimental Therapeutics, Graduate School of Medicine, Akita University, Akita, Japan; and.
Yumiko
Y
Imai
5 LTT Bio-Pharma Co., Ltd., Tokyo, Japan.
Tohru
T
Mizushima
D000818:Animals; D002432:Cecum / Q000473:pathology; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D008026:Ligation; D008070:Lipopolysaccharides; D055370:Lung Injury / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009102:Multiple Organ Failure / Q000150:complications / Q000473:pathology; D010713:Phosphatidylcholines / Q000494:pharmacology / Q000627:therapeutic use*; D011677:Punctures; D017382:Reactive Oxygen Species / Q000378:metabolism; D012121:Respiration, Artificial; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000517:prevention & control*; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use; D013482:Superoxide Dismutase / Q000494:pharmacology / Q000627:therapeutic use*
D008070:Lipopolysaccharides; D010713:Phosphatidylcholines; D017382:Reactive Oxygen Species; D013449:Sulfonamides; D003907:Dexamethasone; C069195:sivelestat; D013482:Superoxide Dismutase; C434045:lecithinized superoxide dismutase; D005998:Glycine
acute respiratory distress syndrome; lecithinized superoxide dismutase; ventilator-induced lung injury