Lopez Esther, del Carmen Ortega-Liébana María, Salido Sofía, Salido Ginés M, Altarejos Joaquín, Rosado Juan A, Redondo Pedro C
Department of Physiology, University of Extremadura, Av. Universidad s/n, 10003, Cáceres, Spain.
J Physiol Biochem. 2015 Sep;71(3):415-34. doi: 10.1007/s13105-015-0421-0. Epub 2015 Jun 17.
Beneficial effects of the antioxidant L-ascorbic acid (Asc) in human health are well known. Its particular role in hemostasis deserves further consideration, since it has been described a dose-dependent effect of Asc in platelet activity. Contrary, it has been demonstrated that phenolic compounds have inhibitory effects on platelet aggregation stimulated by the physiological agonist thrombin (Thr). Here, we have evaluated the actions of three synthetic phenolic esters of Asc: L-ascorbyl 6-protocatechuate (Prot Asc), L-ascorbyl 6-gallate (Gal Asc), and L-ascorbyl 6-caffeate (Caf Asc). All these Asc derivatives exhibited greater radical scavenging activity than Asc, and in experiments using human platelets from healthy subjects, they do not evoke changes in platelet viability upon their administration. Nevertheless, these compounds altered platelet calcium homeostasis in response to Thr, although Prot Asc induced a smaller effect than Gal Asc, Caf Asc, and Asc. As a consequence, platelet aggregation was also impaired by these compounds, reporting Prot Asc and Caf Asc a weaker antiaggregant action than Gal Asc and Asc. Treatments with Gal Asc and Caf Asc altered in larger extent the phosphorylation pattern of pp60(Src) and mammalian target of rapamycin (mTOR) evoked by stimulating human platelets with Thr. Summarizing, Prot Asc is the ascorbyl phenolic ester with the strongest antioxidant properties and weakest antiaggregant actions, and its use as antioxidant may be safer than the rest of derivatives in order to prevent thrombotic alteration in patients that need treatment with antioxidant therapies.
抗氧化剂L-抗坏血酸（Asc）对人体健康的有益作用是众所周知的。其在止血中的特殊作用值得进一步研究，因为已有报道称Asc对血小板活性具有剂量依赖性作用。相反，已证明酚类化合物对生理激动剂凝血酶（Thr）刺激的血小板聚集具有抑制作用。在此，我们评估了三种Asc的合成酚酯的作用：L-抗坏血酸6-原儿茶酸酯（Prot Asc）、L-抗坏血酸6-没食子酸酯（Gal Asc）和L-抗坏血酸6-咖啡酸酯（Caf Asc）。所有这些Asc衍生物均表现出比Asc更强的自由基清除活性，并且在使用健康受试者的人血小板进行的实验中，给药后它们不会引起血小板活力的变化。然而，这些化合物会响应Thr改变血小板钙稳态，尽管Prot Asc诱导的作用比Gal Asc、Caf Asc和Asc小。因此，这些化合物也会损害血小板聚集，据报道Prot Asc和Caf Asc的抗聚集作用比Gal Asc和Asc弱。用Gal Asc和Caf Asc处理在更大程度上改变了用Thr刺激人血小板所引起的pp60(Src)和雷帕霉素哺乳动物靶标（mTOR）的磷酸化模式。总之，Prot Asc是具有最强抗氧化特性和最弱抗聚集作用的抗坏血酸酚酯，对于需要接受抗氧化疗法治疗的患者，为预防血栓形成改变，将其用作抗氧化剂可能比其他衍生物更安全。
