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

机译：琥珀酸抗血小板效应的研究（AGI-1067）

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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：琥珀酚是一种酚类抗氧化剂，具有抗炎和抗血小板作用。鉴于氧化应激在调节血小板和血小板-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与琥珀酚的抗血小板活性有关。在兔全血和富含血小板的血浆中，用阻抗聚集仪研究了胶原和二磷酸腺苷（ADP）对血小板聚集的反应。用黄嘌呤和黄嘌呤氧化酶（X/XO）组合培养血小板、洗涤血小板或预收紧兔髂动脉环，研究氧化应激对聚集、血小板脂质过氧化物和血管张力的影响。为了研究琥珀酚在体内的作用，给麻醉大鼠注射高达150 mg/kg的琥珀酚，并在15分钟后取出的血液中测量聚集性。琥珀酚（10（-5）-10（-4）M）显著减弱全血和富含血小板血浆中血小板对胶原和ADP的聚集。X/XO显著增加了胶原和血小板脂质过氧化物的聚集，琥珀酚可逆转这一现象。在去势的兔髂动脉中加入X/XO可引起剂量依赖性舒张，而琥珀酚可显著抑制这种舒张。150 mg/kg的体内给药对心率或平均动脉血压没有影响，但在体外显著抑制血小板对胶原的聚集。总之，琥珀酚在兔和大鼠血液中显示抗血小板活性，并逆转氧化应激引起的血小板聚集增加。

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