Thrombolytic effects of the snake venom disintegrin saxatilin determined by novel assessment methods

A FeCl3-induced thrombosis model in mice

Il Kwon, Sung Yu Hong, Young Dae Kim, Hyo Suk Nam, Sungsoo Kang, Seung Hee Yang, Jihoe Heo

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 α 2bβ3 (GP IIb/IIIa), α5β 1, αvβ3, α vβ1, 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.

Original languageEnglish
Article numbere81165
JournalPloS one
Volume8
Issue number11
DOIs
Publication statusPublished - 2013 Nov 18

Fingerprint

Disintegrins
Snake Venoms
thrombosis
venoms
snakes
integrins
Thrombosis
animal models
dosage
Platelets
blood flow
glycoproteins
mice
platelet activation
flowmeters
fibrin
carotid arteries
platelet aggregation
fibrinogen
Blood Platelets

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Kwon, Il ; Hong, Sung Yu ; Kim, Young Dae ; Nam, Hyo Suk ; Kang, Sungsoo ; Yang, Seung Hee ; Heo, Jihoe. / Thrombolytic effects of the snake venom disintegrin saxatilin determined by novel assessment methods : A FeCl3-induced thrombosis model in mice. In: PloS one. 2013 ; Vol. 8, No. 11.
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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 α 2bβ3 (GP IIb/IIIa), α5β 1, αvβ3, α vβ1, 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.",
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Thrombolytic effects of the snake venom disintegrin saxatilin determined by novel assessment methods : A FeCl3-induced thrombosis model in mice. / Kwon, Il; Hong, Sung Yu; Kim, Young Dae; Nam, Hyo Suk; Kang, Sungsoo; Yang, Seung Hee; Heo, Jihoe.

In: PloS one, Vol. 8, No. 11, e81165, 18.11.2013.

Research output: Contribution to journalArticle

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