Effects of edaravone, a free-radical scavenger, on bleomycin-induced lung injury in mice.
Reactive oxygen species play an important role in the pathogenesis of acute lung injury and pulmonary fibrosis. The present authors hypothesise that edaravone, a free-radical scavenger, is able to attenuate bleomycin (BLM)-induced lung injury in mice by decreasing oxidative stress. Lung injury was induced in female ICR mice by intratracheal instillation of 5 mg x kg(-1) of BLM. Edaravone (300 mg x kg(-1)) was administered by intraperitoneal administration 1 h before BLM challenge. Edaravone significantly improved the survival rate of mice treated with BLM from 25 to 90%, reduced the number of total cells and neutrophils in bronchoalveolar lavage fluid (BALF) on day 7, and attenuated the concentrations of lipid hydroperoxide in BALF and serum on day 2. The fibrotic change in the lung on day 28 was ameliorated by edaravone, as evaluated by histological examination and measurement of hydroxyproline contents. In addition, edaravone significantly increased the prostaglandin E(2) concentration in BALF on day 2. In summary, edaravone was shown to inhibit lung injury and fibrosis via the repression of lipid hydroperoxide production and the elevation of prostaglandin E(2) production in the present experimental murine system.
Tajima
S
S
Division of Pulmonary Medicine, Dept of Medicine, Jichi Medical University, Shimotsuke, Japan. tajimash@med.niigata-u.ac.jp
Bando
M
M
Ishii
Y
Y
Hosono
T
T
Yamasawa
H
H
Ohno
S
S
Takada
T
T
Suzuki
E
E
Gejyo
F
F
Sugiyama
Y
Y
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001761:Bleomycin / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid; D015232:Dinoprostone / Q000378:metabolism; D000077553:Edaravone; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D008055:Lipids / Q000737:chemistry; D008168:Lung / Q000187:drug effects*; D055370:Lung Injury / Q000139:chemically induced* / Q000188:drug therapy*; D051379:Mice; D008813:Mice, Inbred ICR; D018384:Oxidative Stress; D011658:Pulmonary Fibrosis / Q000188:drug therapy; D017382:Reactive Oxygen Species
D016166:Free Radical Scavengers; D008055:Lipids; D017382:Reactive Oxygen Species; D001761:Bleomycin; D015232:Dinoprostone; D000077553:Edaravone; D000983:Antipyrine