The Free Radical Scavenger Edaravone Rescues Rats from Cerebral Infarction by Attenuating the Release of High-Mobility Group Box-1 in Neuronal Cells

被引：60

作者：

Kikuchi, Kiyoshi ^{[1
,7
]}

Kawahara, Ko-ichi ^{[1
]}

Tancharoen, Salunya ^{[4
]}

Matsuda, Fumiyo ^{[5
]}

Morimoto, Yoko ^{[2
]}

Ito, Takashi ^{[1
]}

Biswas, Kamal Krishna ^{[1
]}

Takenouchi, Kazunori ^{[1
]}

Miura, Naoki ^{[6
]}

Oyama, Yoko ^{[1
]}

Nawa, Yuko ^{[1
]}

Arimura, Noboru ^{[1
]}

Iwata, Masahiro ^{[3
]}

Tajima, Yutaka ^{[7
]}

Kuramoto, Terukazu ^{[7
]}

Nakayama, Kenji ^{[7
]}

Shigemori, Minoru ^{[8
]}

Yoshida, Yoshihiro ^{[5
]}

Hashiguchi, Teruto ^{[1
]}

Maruyama, Ikuro ^{[1
]}

机构：

[1] Kagoshima Univ, Grad Sch Med & Dent Sci, Div Lab & Vasc Med, Field Cardiovasc & Resp Disorders,Dept Adv Therap, Kagoshima 8908520, Japan

[2] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Periodontol, Kagoshima 8908520, Japan

[3] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Dermatol, Kagoshima 8908520, Japan

[4] Mahidol Univ, Fac Dent, Dept Pharmacol, Bangkok 10700, Thailand

[5] Kagoshima Univ, Sch Hlth Sci, Fac Med, Div Phys Therapy, Kagoshima 8908520, Japan

[6] Kagoshima Univ, Dept Vet Med, Fac Agr, Lab Vet Diagnost Imaging, Kagoshima 8908520, Japan

[7] Omuta City Gen Hosp, Dept Neurosurg, Omuta, Japan

[8] Kurume Univ, Dept Neurosurg, Fac Med, Kurume, Fukuoka 830, Japan

来源：

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS | 2009年 / 329卷 / 03期

关键词：

ACTIVATED PROTEIN-KINASES; END-PRODUCTS RAGE; INDUCED APOPTOSIS; ARTERY OCCLUSION; BRAIN EDEMA; ISCHEMIA; STRESS; HMGB1; RESPONSES; MCI-186;

D O I：

10.1124/jpet.108.149484

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Edaravone, a potent free radical scavenger, is clinically used for the treatment of cerebral infarction in Japan. Here, we examined the effects of edaravone on the dynamics of high-mobility group box-1 (HMGB1), which is a key mediator of ischemic-induced brain damage, during a 48-h postischemia/reperfusion period in rats and in oxygen-glucose-deprived (OGD) PC12 cells. HMGB1 immunoreactivity was observed in both the cytoplasm and the periphery of cells in the cerebral infarction area 2 h after reperfusion. Intravenous administration of 3 and 6 mg/kg edaravone significantly inhibited nuclear translocation and HMGB1 release in the penumbra area and caused a 26.5 +/- 10.4 and 43.8 +/- 0.5% reduction, respectively, of the total infarct area at 24 h after reperfusion. Moreover, edaravone also decreased plasma HMGB1 levels. In vitro, edaravone dose-dependently (1-10 mu M) suppressed OGD- and H2O2-induced HMGB1 release in PC12 cells. Furthermore, edaravone (3-30 mu M) blocked HMGB1-triggered apoptosis in PC12 cells. Our findings suggest a novel neuroprotective mechanism for edaravone that abrogates the release of HMGB1.

引用

页码：865 / 874

页数：10

共 56 条

[51] Activation of mitogen-activated protein kinases after permanent cerebral artery occlusion in mouse brain [J].