An investigation of the antiplatelet effects of succinobucol (AGI-1067)
An investigation of the antiplatelet effects of succinobucol (AGI-1067)
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DOI：
10.1080/09537104.2016.1218456
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发表时间：
2017-01-01
期刊：
影响因子：
3.3
通讯作者：
Kennedy, Simon
中科院分区：
文献类型：
--
作者：
Houston, Stephanie A.;Ugusman, Azizah;Kennedy, Simon
丁二酚是一种酚类抗氧化剂，具有抗炎和抗血小板作用。考虑到氧化应激在调节血小板-血小板和血小板-血管壁相互作用中的重要性，本研究的目的是确定抗氧化活性是否是琥珀酸抗血小板活性的原因。用阻抗法研究了胶原和二磷酸腺苷（ADP）对兔全血和富血小板血浆血小板聚集的影响。用黄嘌呤和黄嘌呤氧化酶（X/XO）联合孵育血小板、洗涤血小板和预缩兔髂动脉环，研究氧化应激对血小板聚集、血小板脂质过氧化物和血管张力的影响。为了研究琥珀酰丁二醇在体内的作用，给麻醉大鼠注射高达150 mg/kg的琥珀酰丁二醇，15分钟后在血液中测量聚集。在全血和富血小板血浆中，琥珀酸（10（-5）-10（-4）M）显著减弱血小板对胶原和ADP的聚集。X/XO显着增加胶原和血小板脂质过氧化物的聚集，这是逆转琥珀丁二醇。X/XO对兔髂动脉的舒张作用呈剂量依赖性，琥珀酸可明显抑制X/XO的舒张作用。高达150 mg/kg的体内给药对心率或平均动脉血压没有影响，但显著抑制了离体血小板聚集成胶原蛋白。总之，琥珀酸在兔和大鼠血液中显示出抗血小板活性，并逆转血小板聚集增加对氧化应激的反应。
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.