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Oxidative Medicine and Cellular Longevity
Volume 2017, Article ID 6873281, 14 pages
https://doi.org/10.1155/2017/6873281
Research Article

Edaravone, a Synthetic Free Radical Scavenger, Enhances Alteplase-Mediated Thrombolysis

1Division of Brain Science, Department of Physiology, Kurume University School of Medicine, Kurume, Japan
2Department of Neurosurgery, Kurume University School of Medicine, Kurume, Japan
3Department of Systems Biology in Thromboregulation, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima, Japan
4Department of Pharmacology, Faculty of Dentistry, Mahidol University, Bangkok, Thailand
5Division of Laboratory Animal Science, Natural Science Center for Research and Education, Kagoshima University, Kagoshima, Japan
6Department of Biomedical Engineering, Laboratory of Functional Foods, Osaka Institute of Technology, Osaka, Japan
7Research Institute, Fujimori Kogyo Co., Yokohama, Kanagawa, Japan
8Course of Physical Therapy, School of Health Sciences, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
9Department of Veterinary Science, Laboratory of Diagnostic Imaging, Faculty of Agriculture, Kagoshima University, Kagoshima, Japan
10Department of Restorative Dentistry and Endodontology, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima, Japan
11Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima, Japan
12School of Health Sciences, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
13Department of Emergency and Critical Care Medicine, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima, Japan

Correspondence should be addressed to Takashi Ito; pj.ca.u-amihsogak.mfuk.3m@ihsakat and Ikuro Maruyama; pj.ca.u-amihsogak.mfuk.2m@amayuram

Received 7 July 2017; Accepted 7 September 2017; Published 10 November 2017

Academic Editor: Adrian Doroszko

Copyright © 2017 Kiyoshi Kikuchi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.