Hydroxytyrosyl alkyl ether derivatives inhibit platelet activation after oral administration to rats
Hydroxytyrosyl alkyl ether derivatives inhibit platelet activation after oral administration to rats
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DOI：
10.1016/j.fct.2013.04.045
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发表时间：
2013-08-01
影响因子：
4.3
通讯作者：
Antonio Gonzalez-Correa, Jose
中科院分区：
文献类型：
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作者：
Munoz-Marin, Javier;Pedro De La Cruz, Jose;Antonio Gonzalez-Correa, Jose
羟基酪醇（HT）的低亲脂性促使人们努力合成具有更好脂溶性的同系物，例如比HT更亲脂的醚类。由于HT抑制血小板聚集，该研究的目的是评估五种HT醚衍生物（乙基、丁基、己基、辛基和十二烷基）给大鼠口服后可能的抗血小板作用。测量全血胶原诱导的血小板聚集和钙诱导的血栓素 B-2 (TxB(2))、主动脉 6-酮-前列腺素 F-1 α (6-酮-PGF(1 α)) 和亚硝酸盐 + 硝酸盐、脂质过氧化物 (TBARS) 血浆浓度和还原型谷胱甘肽 (GSH) 红细胞含量。 20mg/kg/天的给药以与碳链长度相关的非线性方式抑制血小板聚集、TxB(2)和TBARS，并在己基衍生物中具有截止作用。主动脉亚硝酸盐和红细胞谷胱甘肽的产生也增加。除了用十二烷基衍生物治疗的组外，主动脉产生的 6-酮基-PGF(1α) 没有改变。 50 mg/kg/天的给药表现出相似的药效学特征，但没有非线性效应。总之，HT 醚，尤其是己基衍生物，是羟基酪醇的潜在替代品，其作用值得进一步研究以确定其在预防血管疾病中的作用。 (C) 2013 Elsevier Ltd. 保留所有权利。
The low lipophilicity of hydroxytyrosol (HT) has motivated efforts to synthesize homologous series with better lipid solubility, such as the ethers, which are more lipophilic than HT. Because HT inhibits platelet aggregation, the aim of the study was to assess the possible anti-platelet effect of five HT ether derivatives (ethyl, butyl, hexyl, octyl and dodecyl) after oral administration to rats. Whole blood collagen-induced platelet aggregation and calcium-induced thromboxane B-2 (TxB(2)) aortic 6-keto-prostaglandin F-1 alpha (6-keto-PGF(1 alpha)) and nitrites + nitrates, plasma concentration of lipid peroxides (TBARS) and red blood cell content of reduced glutathione (GSH) were measured. The administration of 20 mg/kg/day inhibited platelet aggregation, TxB(2) and TBARS in a non-linear manner related to the length of the carbon chain, with a cut-off effect in the hexyl derivative. Aortic nitrite and red blood cell GSH production were also increased. The aortic production of 6-keto-PGF(1 alpha), was unaltered except in the group treated with the dodecyl derivative. The administration of 50 mg/kg/day showed a similar pharmacodynamic profile but without the non-linear effect. In conclusion, HT ethers, especially the hexyl derivative, are a potential alternative to hydroxytyrosol, and their effect merits additional research to determine their role in the prophylaxis of vascular disease. (C) 2013 Elsevier Ltd. All rights reserved.