Free radical scavenger (edaravone) prevents endotoxin-induced liver injury after partial hepatectomy in rats.
OBJECTIVE
Infection after major surgery, such as massive hepatectomy, induces liver dysfunction, occasionally leading to multiple organ failure and death. We demonstrated the anti-inflammatory effects and functional mechanisms of 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone), a newly synthesized free radical scavenger, on an experimental model of endotoxemia after partial hepatectomy in rats.


METHODS
Rats were treated with lipopolysaccharide (LPS) 48h after 70% hepatectomy. Edaravone was administered intravenously before LPS-treatment.


RESULTS
Edaravone markedly improved the survival rate of LPS-treated rats after hepatectomy and inhibited increases in serum levels of AST and LDH. Histopathological analysis demonstrated that edaravone prevented inflammatory changes in the liver, kidney and spleen. Edaravone inhibited the formation of one of the markers of oxidative damage, malondialdehyde. Increases in inflammatory cytokines and cytokine-induced neutrophil chemoattractant (CINC) in serum and liver tissue were inhibited in the edaravone-treated group. An electrophoretic mobility shift assay revealed that edaravone inhibited the activation of the transcription factor, nuclear factor-kappa B (NF-kappaB). Edaravone also reduced the induction of inducible nitric oxide synthase (iNOS).


CONCLUSIONS
Edaravone prevents endotoxin-induced liver injury after partial hepatectomy not only by attenuating oxidative damage, but also by reducing the production of inflammatory cytokines, CINC and iNOS, in part through the inhibition of NF-kappaB activation.
Tsuji
Katsushige
K
Department of Surgery, Kansai Medical University, 10-15 Fumizono, Moriguchi, Osaka 570-8507, Japan.
Kwon
A-Hon
AH
Yoshida
Hideyuki
H
Qiu
Zeyu
Z
Kaibori
Masaki
M
Okumura
Tadayoshi
T
Kamiyama
Yasuo
Y
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001663:Bilirubin / Q000097:blood; D016207:Cytokines / Q000097:blood; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley
D016207:Cytokines; D016166:Free Radical Scavengers; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D000410:Alanine Transaminase; D001663:Bilirubin; D000077553:Edaravone; D000983:Antipyrine