The specific free radical scavenger edaravone suppresses bleomycin-induced acute pulmonary injury in rabbits.
1. Intratracheal instillation of bleomycin induces a condition in rabbits that serves as a useful model of human pulmonary fibrosis. Bleomycin-induced production of reactive oxygen species leads to acute lung inflammation and induction of apoptosis, which is followed by pulmonary fibrosis at a later chronic stage. In the present study, we tested whether edaravone, a free radical scavenger, would suppress bleomycin-induced acute pulmonary inflammation. 2. Rabbits were divided into three groups (n = 10 in each): (i) a bleomycin-treated group, which received intratracheal instillation of 2 mg/kg bleomycin; (ii) a bleomycin + edaravone group, which received a 10 day regimen of daily intravenous injections of edaravone (3 mg/kg per day) beginning 3 days before bleomycin instillation; and (iii) a saline control group. Rabbits were killed for analysis 7 days after bleomycin administration. 3. In lung tissues from the bleomycin-treated group, marked infiltration of inflammatory cells, consisting mainly of lymphocytes, neutrophils and eosinophils, was observed. In addition, significantly increased numbers of TUNEL-positive (apoptotic) and transforming growth factor-beta-positive cells were seen. All these effects were significantly attenuated by treatment with edaravone. 4. The findings of the present study suggest that edaravone may be useful in the prevention of acute lung injury resulting from the production of reactive oxygen species.
Asai
Toshihiro
T
Second Department of Internal Medicine, Regeneration and Advanced Medical Science, Graduate School of Medicine, Gifu University, Gifu, Japan.
Ohno
Yasushi
Y
Minatoguchi
Shinya
S
Funaguchi
Norihiko
N
Yuhgetsu
Hideyuki
H
Sawada
Masahiro
M
Takemura
Genzou
G
Komada
A
A
Fujiwara
Takako
T
Fujiwara
Hisayoshi
H
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis; D001761:Bleomycin; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011817:Rabbits; D016212:Transforming Growth Factor beta / Q000378:metabolism
D016166:Free Radical Scavengers; D016212:Transforming Growth Factor beta; D001761:Bleomycin; D020781:Matrix Metalloproteinase 1; D000077553:Edaravone; D000983:Antipyrine