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

机译：琥珀酰胆碱（aGI-1067）抗血小板作用的研究

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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.
机译：琥珀醇是一种具有抗炎和抗血小板作用的酚类抗氧化剂。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剂活性是否对丁二酚的抗血小板活性负责。在兔全血和富含血小板的血浆中使用阻抗聚集法研究了对胶原蛋白和二磷酸腺苷（ADP）响应的血小板聚集。通过将黄嘌呤和黄嘌呤氧化酶（X / XO）分别孵育血小板，洗涤过的血小板或预收缩的兔动脉环，研究了氧化应激对聚集，血小板脂质过氧化物和血管紧张的影响。为了研究琥珀丁醇在体内的作用，向麻醉的大鼠注射高达150 mg / kg的琥珀丁醇，并在15分钟后去除血液中的聚集。琥珀醇（10−5–10−4 M）在全血和富含血小板的血浆中显着减弱血小板向胶原蛋白和ADP的聚集。 X / XO显着增加了胶原和血小板脂质过氧化物的聚集，琥珀丁醇逆转了这一现象。在裸露的兔动脉中添加X / XO会引起剂量依赖性舒张，而琥珀丁醇显着抑制了舒张。体内最高150 mg / kg的给药对心率或平均动脉血压没有影响，但离体胶原蛋白显着抑制了血小板聚集。总之，琥珀酰丁醇在兔和大鼠血液中显示抗血小板活性，并响应于氧化应激而逆转血小板聚集的增加。

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