Publication: Edaravone, a synthetic free radical scavenger, enhances alteplase-mediated thrombolysis
Issued Date
2017-01-01
Resource Type
ISSN
19420994
19420900
19420900
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2-s2.0-85042597082
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Mahidol University
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SCOPUS
Bibliographic Citation
Oxidative Medicine and Cellular Longevity. Vol.2017, (2017)
Suggested Citation
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 Edaravone, a synthetic free radical scavenger, enhances alteplase-mediated thrombolysis. Oxidative Medicine and Cellular Longevity. Vol.2017, (2017). doi:10.1155/2017/6873281 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/42040
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Title
Edaravone, a synthetic free radical scavenger, enhances alteplase-mediated thrombolysis
Author(s)
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
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
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.