Preventive effects of edaravone, a free radical scavenger, on lipopolysaccharide-induced lung injury in mice.
OBJECTIVE
Reactive oxygen species (ROS) play an important role in the pathogenesis of acute lung injury (ALI) and pulmonary fibrosis. It was hypothesized that edaravone, a free radical scavenger, would be able to attenuate LPS-induced lung injury in mice by decreasing oxidative stress.


METHODS
For the in vivo experiments, lung injury was induced in female BALB/c mice by the intranasal instillation of LPS. Edaravone was given by intraperitoneal administration 1 h before the LPS challenge. For the in vitro experiments, MH-S cells (murine alveolar macrophage cell line) were exposed to edaravone, followed by stimulation with LPS.


RESULTS
In the LPS-induced ALI mouse model, the administration of edaravone attenuated cellular infiltration into and the concentrations of albumin, IL-6, tumour necrosis factor-alpha, keratinocyte-derived chemokine and macrophage inflammatory protein-2 in BAL fluid. In addition, the in vitro studies showed that the elevated IL-6 secretion from MH-S cells in response to LPS was significantly attenuated by co-incubation with edaravone.


CONCLUSIONS
In an experimental murine model, a free radical scavenger may prevent ALI via repression of pro-inflammatory cytokine production by lung macrophages.
Tajima
Shunji
S
Department of Medicine, Division of Pulmonary Medicine, Jichi Medical University, Tochigi, Japan. tajimash@med.niigata-u.ac.jp
Soda
Manabu
M
Bando
Masashi
M
Enomoto
Munehiro
M
Yamasawa
Hideaki
H
Ohno
Shoji
S
Takada
Toshinori
T
Suzuki
Eiichi
E
Gejyo
Fumitake
F
Sugiyama
Yukihiko
Y
D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control*; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002460:Cell Line; D054426:Chemokine CXCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D000077553:Edaravone; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D016166:Free Radical Scavengers; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000077553:Edaravone; D000983:Antipyrine