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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/42040
Title: Edaravone, a synthetic free radical scavenger, enhances alteplase-mediated thrombolysis
Authors: Kiyoshi Kikuchi
Kentaro Setoyama
Ko Ichi Kawahara
Tomoka Nagasato
Takuto Terashi
Koki Ueda
Kazuki Nakanishi
Shotaro Otsuka
Naoki Miura
Hisayo Sameshima
Kazuya Hosokawa
Yoichiro Harada
Binita Shrestha
Mika Yamamoto
Yoko Morimoto-Yamashita
Haruna Kikuchi
Ryoji Kiyama
Chinatsu Kamikokuryo
Salunya Tancharoen
Harutoshi Sakakima
Motohiro Morioka
Eiichiro Tanaka
Takashi Ito
Ikuro Maruyama
Kurume University School of Medicine
Kagoshima University
Mahidol University
Osaka Institute of Technology
Fujimori Kogyo Co.
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Jan-2017
Citation: Oxidative Medicine and Cellular Longevity. Vol.2017, (2017)
Abstract: © 2017 Kiyoshi Kikuchi et al. The combination of alteplase, a recombinant tissue plasminogen activator, and edaravone, an antioxidant, reportedly enhances recanalization after acute ischemic stroke. We examined the influence of edaravone on the thrombolytic efficacy of alteplase by measuring thrombolysis using a newly developed microchip-based flow-chamber assay. Rat models of embolic cerebral ischemia were treated with either alteplase or alteplase-edaravone combination therapy. The combination therapy significantly reduced the infarct volume and improved neurological deficits. Human blood samples from healthy volunteers were exposed to edaravone, alteplase, or a combination of alteplase and edaravone or hydrogen peroxide. Whole blood was perfused over a collagen- and thromboplastin-coated microchip; capillary occlusion was monitored with a video microscope and flow-pressure sensor. The area under the curve (extent of thrombogenesis or thrombolysis) at 30 minutes was 69.9% lower in the edaravone-alteplase- than alteplase-treated group. The thrombolytic effect of alteplase was significantly attenuated in the presence of hydrogen peroxide, suggesting that oxidative stress might hinder thrombolysis. D-dimers were measured to evaluate these effects in human platelet-poor plasma samples. Although hydrogen peroxide significantly decreased the elevation of D-dimers by alteplase, edaravone significantly inhibited the decrease. Edaravone enhances alteplase-mediated thrombolysis, likely by preventing oxidative stress, which inhibits fibrinolysis by alteplase in thrombi.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85042597082&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/42040
ISSN: 19420994
19420900
Appears in Collections:Scopus 2016-2017

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