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Title: Uric acid enhances alteplase-mediated thrombolysis as an antioxidant
Authors: Kiyoshi Kikuchi
Kentaro Setoyama
Eiichiro Tanaka
Shotaro Otsuka
Takuto Terashi
Kazuki Nakanishi
Seiya Takada
Harutoshi Sakakima
Sumate Ampawong
Ko ichi Kawahara
Tomoka Nagasato
Kazuya Hosokawa
Yoichiro Harada
Mika Yamamoto
Chinatsu Kamikokuryo
Ryoji Kiyama
Motohiro Morioka
Takashi Ito
Ikuro Maruyama
Salunya Tancharoen
Osaka Institute of Technology
Kagoshima University
Mahidol University
Kurume University School of Medicine
Fujimori Kogyo Co.
Keywords: Multidisciplinary
Issue Date: 1-Dec-2018
Citation: Scientific Reports. Vol.8, No.1 (2018)
Abstract: © 2018, The Author(s). Uric acid (UA) therapy may prevent early ischemic worsening after acute stroke in thrombolysis patients. The aim of this study was to examine the influence of UA on the thrombolytic efficacy of alteplase in human blood samples by measuring thrombolysis under flow conditions using a newly developed microchip-based flow-chamber assay. Human blood samples from healthy volunteers were exposed to UA, alteplase, or a combination of UA and alteplase. Whole blood and platelet-rich plasma were perfused over a collagen- and thromboplastin-coated microchip, and 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 92% lower in the UA–alteplase-treated group compared with the alteplase-treated group. 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, UA significantly inhibited the effect of hydrogen peroxide. Meanwhile, rat models of thromboembolic cerebral ischemia were treated with either alteplase or UA–alteplase combination therapy. Compared with alteplase alone, the combination therapy reduced the infarct volume and inhibited haemorrhagic transformation. UA enhances alteplase-mediated thrombolysis, potentially by preventing oxidative stress, which inhibits fibrinolysis by alteplase in thrombi.
ISSN: 20452322
Appears in Collections:Scopus 2018

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