A free radical scavenger, edaravone, attenuates steatosis and cell death via reducing inflammatory cytokine production in rat acute liver injury.
OBJECTIVE
Reactive oxygen radicals play an important role in various forms of liver injury. In this study, we evaluated the efficacy of edaravone, a newly synthesized free radical scavenger, in its clinical dosage on an experimental model of acute liver injury in rats.


METHODS
The clinical dose of edaravone (3 mg/kg) was intravenously administered immediately and 3 h after intraperitoneal administration of carbon tetrachloride (CCl4) in rats. Histological evaluation including apoptosis and cytokine profiles were examined.


RESULTS
Fatty degeneration and necrosis with marked elevation of serum alanine aminotransferase and lactate dehydrogenase levels developed after CCl4 administration were significantly reduced by edaravone. In addition, the apoptotic index assessed by TUNEL method was significantly lowered in the edaravone treated group. Serum and liver transcription levels of interleukin-6, tumor necrosis factor-alpha, interleukin-4, and interleukin-10 were increased following CCl4 administration, and they were attenuated by edaravone treatment. The formation of malondialdehyde, 4-hydroxynonenal adduct and one of the markers for oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine, was also inhibited by edaravone treatment.


CONCLUSIONS
Edaravone has a remarkable protective effect on acute liver injury caused by oxygen radicals through not only attenuating the membrane lipid peroxidation, but also inhibiting the production of inflammatory cytokines. We theorize that edaravone may have a clinical benefit in the treatment of various liver injuries.
Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Nobuhiro
N
Nakamoto
Shinichiro
S
Tada
Kaori
K
Kameyama
Kumi
K
Kitamura
Satoshi
S
Kurita
Yoshimasa
Y
Saito
Hidetsugu
H
Saito
Hiromasa
H
Ishii
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000208:Acute Disease; D000410:Alanine Transaminase / Q000097:blood; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017209:Apoptosis; D016923:Cell Death; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology; D006131:Growth Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000293:injuries* / Q000378:metabolism; D008297:Male; D008956:Models, Chemical; D009336:Necrosis; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000447:Aldehydes; D016207:Cytokines; D016166:Free Radical Scavengers; D006131:Growth Inhibitors; D015850:Interleukin-6; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D000080242:8-Hydroxy-2'-Deoxyguanosine; D000410:Alanine Transaminase; D003849:Deoxyguanosine; C027576:4-hydroxy-2-nonenal; D000077553:Edaravone; D010100:Oxygen; D000983:Antipyrine