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Thrombolytic Effects of the Snake Venom Disintegrin Saxatilin Determined by Novel Assessment Methods: A FeCl3-Induced Thrombosis Model in Mice.

Authors
 Il Kwon  ;  Sung-Yu Hong  ;  Young Dae Kim  ;  Hyo Suk Nam  ;  Sungsoo Kang  ;  Seung-Hee Yang  ;  Ji Hoe Heo 
Citation
 PLOS ONE, Vol.8(11) : e81165, 2013 
Journal Title
 PLOS ONE 
Issue Date
2013
Abstract
Saxatilin, a novel disintegrin purified and cloned from the venom of the Korean snake Gloydius saxatilis, strongly inhibits activation and aggregation of platelets. Glycoprotein (GP) IIb/IIIa receptor antagonists can resolve thrombus, so saxatilin might also have thrombolytic effects. We investigated the thrombolytic effects of saxatilin in mice using a ferric chloride-induced carotid arterial thrombosis model. Thrombotic occlusion and thrombus resolution were evaluated quantitatively by measuring blood flow in the carotid artery with an ultrasonic flow meter and calculating the degree of flow restoration on a minute-by-minute basis; results were confirmed by histological examination. Saxatilin dissolved thrombi in a dose-dependent manner. Saxatilin at 5 mg/kg restored blood flow to baseline levels. As saxatilin dose increased, time to recanalization decreased. A bolus injection of 10% of a complete dose with continuous infusion of the remaining dose for 60 minutes resulted in effective recanalization without reocclusion. The thrombolytic effect of saxatilin was also demonstrated in vitro using platelet aggregometry by administering saxatilin in preformed thrombi. Bleeding complications were observed in 2 of 71 mice that received saxatilin. Fibrin/fibrinogen zymography and platelet aggregometry studies indicated that saxatilin does not have fibrinolytic activity, but exerted its action on platelets. Integrin-binding assays showed that saxatilin inhibited multiple integrins, specifically α2bβ3 (GP IIb/IIIa), α5β1, αvβ3, αvβ1, and αvβ5, which act on platelet adhesion/aggregation. Saxatilin inhibited multiple integrins by acting on platelets, and was safe and effective in resolving thrombi in mice.
Files in This Item:
T201304032.pdf Download
DOI
10.1371/journal.pone.0081165
Appears in Collections:
5. Research Institutes (연구소) > Cardiovascular Product Evaluation Center (심혈관제품유효성평가센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Sung Soo(강성수)
Kwon, Il(권일) ORCID logo https://orcid.org/0000-0001-9449-5646
Kim, Young Dae(김영대) ORCID logo https://orcid.org/0000-0001-5750-2616
Nam, Hyo Suk(남효석) ORCID logo https://orcid.org/0000-0002-4415-3995
Yang, Seung Hee(양승희)
Heo, Ji Hoe(허지회) ORCID logo https://orcid.org/0000-0001-9898-3321
Hong, Sung Yu(홍성유)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/88474
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