Effects of reactive oxygen species scavenger on the protective action of 100% oxygen treatment against sterile inflammation in mice.
Sepsis/multiple organ dysfunction syndrome (MODS) is a major cause of high mortality in the intensive care unit. We have recently reported that 100% oxygen treatment is beneficial to mice with zymosan-induced sterile inflammation by increasing antioxidant enzymatic activities. Yet, the use of hyperoxia is hindered by concerns that it could exacerbate organ injury by increasing free radical formation. It is believed that systemic inflammation and overproduction of reactive oxygen species (ROS) contribute to the mechanism underlying sepsis/MODS. A ROS scavenger has been proven to protect against sepsis/MODS in some animal models. Therefore, we hypothesized that ROS scavenger pretreatment might enhance the protective action of 100% oxygen treatment against zymosan-induced sterile inflammation in mice. In the present study, we showed that 100% oxygen treatment prevented the abnormal changes in serum biochemical parameters, tissue oxygenation, and organ histopathology, and improved the 14-day survival rate in zymosan-stimulated mice, indicating that 100% oxygen treatment had a protective action on sterile inflammation. We found that pretreatment with a ROS scavenger (N-acetylcysteine, vitamin C, or dimethylthiourea) abolished this protective action of 100% oxygen treatment. We also showed that 100% oxygen treatment decreased the levels of serum proinflammatory cytokines (TNF-alpha, IL-6, and high-mobility group box 1), increased the level of serum anti-inflammatory cytokine (IL-10), and upregulated the activities of serum and tissue antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) in zymosan-stimulated mice, which were reversed by the pretreatment with a ROS scavenger (N-acetylcysteine, vitamin C, or dimethylthiourea). We thus conclude that ROS scavenger pretreatment partly abolishes the protective effects of 100% oxygen treatment on sterile inflammation in mice by regulating inflammatory cytokines as well as antioxidant enzymes.
Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China. houlc9534@hotmail.com
Lichao
L
Hou
Keliang
K
Xie
Mingzhe
M
Qin
Daorong
D
Peng
Shirong
S
Ma
Lei
L
Shang
Nan
N
Li
Shuzhi
S
Li
Genlin
G
Ji
Yan
Y
Lu
Lize
L
Xiong
D000111:Acetylcysteine / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001205:Ascorbic Acid / Q000009:adverse effects; D016207:Cytokines / Q000097:blood; D016166:Free Radical Scavengers / Q000009:adverse effects / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D009102:Multiple Organ Failure / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D010100:Oxygen / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000494:pharmacology; D018805:Sepsis / Q000517:prevention & control; D013890:Thiourea / Q000009:adverse effects / Q000031:analogs & derivatives; D015054:Zymosan
D000975:Antioxidants; D016207:Cytokines; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; C038983:1,3-dimethylthiourea; D015054:Zymosan; D013890:Thiourea; D001205:Ascorbic Acid; D010100:Oxygen; D000111:Acetylcysteine