An investigation of the antiplatelet effects of succinobucol (AGI-1067)

Stephanie A. Houston, Azizah Ugusman, Sukanya Gnanadesikan, Simon Kennedy

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Succinobucol is a phenolic antioxidant with anti-inflammatory and antiplatelet effects. Given the importance of oxidant stress in modulating platelet–platelet and platelet–vessel wall interactions, the aim of this study was to establish if antioxidant activity was responsible for the antiplatelet activity of succinobucol. Platelet aggregation in response to collagen and adenosine diphosphate (ADP) was studied in rabbit whole blood and platelet-rich plasma using impedance aggregometry. The effect of oxidant stress on aggregation, platelet lipid peroxides, and vascular tone was studied by incubating platelets, washed platelets or preconstricted rabbit iliac artery rings respectively with a combination of xanthine and xanthine oxidase (X/XO). To study the effect of succinobucol in vivo, anaesthetized rats were injected with up to 150 mg/kg succinobucol and aggregation measured in blood removed 15 mins later. Succinobucol (10−5–10−4 M) significantly attenuated platelet aggregation to collagen and ADP in whole blood and platelet-rich plasma. X/XO significantly increased aggregation to collagen and platelet lipid peroxides and this was reversed by succinobucol. Addition of X/XO to denuded rabbit iliac arteries caused a dose-dependent relaxation which was significantly inhibited by succinobucol. In vivo administration up to 150 mg/kg had no effect on heart rate or mean arterial blood pressure but significantly inhibited platelet aggregation to collagen ex vivo. In conclusion, succinobucol displays anti-platelet activity in rabbit and rat blood and reverses the increase in platelet aggregation in response to oxidant stress.

Original languageEnglish
Pages (from-to)1-6
Number of pages6
JournalPlatelets
DOIs
Publication statusAccepted/In press - 30 Sep 2016

Fingerprint

Platelet Aggregation
Blood Platelets
Xanthine
Xanthine Oxidase
Collagen
Oxidants
Rabbits
Platelet-Rich Plasma
Iliac Artery
Lipid Peroxides
Adenosine Diphosphate
Arterial Pressure
Antioxidants
succinobucol
Electric Impedance
Blood Vessels
Anti-Inflammatory Agents
Heart Rate

Keywords

  • Lipid peroxidation
  • platelet aggregation
  • succinobucol
  • superoxide

ASJC Scopus subject areas

  • Hematology

Cite this

An investigation of the antiplatelet effects of succinobucol (AGI-1067). / Houston, Stephanie A.; Ugusman, Azizah; Gnanadesikan, Sukanya; Kennedy, Simon.

In: Platelets, 30.09.2016, p. 1-6.

Research output: Contribution to journalArticle

Houston, Stephanie A. ; Ugusman, Azizah ; Gnanadesikan, Sukanya ; Kennedy, Simon. / An investigation of the antiplatelet effects of succinobucol (AGI-1067). In: Platelets. 2016 ; pp. 1-6.
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