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

Houston, S. A., Ugusman, A., Gnanadesika, S. and Kennedy, S. (2017) An investigation of the antiplatelet effects of succinobucol (AGI-1067). Platelets, 28(3), pp. 295-300. (doi: 10.1080/09537104.2016.1218456) (PMID:27681689)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Kennedy, Professor Simon and Houston, Miss Stephanie
Authors: Houston, S. A., Ugusman, A., Gnanadesika, S., and Kennedy, S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Platelets
Publisher:Taylor & Francis
ISSN:0953-7104
ISSN (Online):1369-1635
Published Online:29 September 2016
Copyright Holders:Copyright © 2016 Stephanie A. Houston, Azizah Ugusman, Sukanya Gnanadesikan, & Simon Kennedy
First Published:First published in Platelets 28(3):295-300
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
534781BBSRC Masters Training Grant 2010Margaret MacLeanBiotechnology and Biological Sciences Research Council (BBSRC)BB/H020675/1RI CARDIOVASCULAR & MEDICAL SCIENCES