Antiplatelet effect of new lipophilic hydroxytyrosol alkyl ether derivatives in human blood
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To investigate the in vitro antiplatelet and anti-inflammatory effects of five alkyl hydroxytyrosol (HT) ether derivatives in human whole blood and compare these effects with those of HT.
Blood samples from healthy volunteers were incubated with HT and HT alkyl ether derivatives (ethyl, butyl, hexyl, octyl and dodecyl). Maximum intensity of platelet aggregation was induced with collagen, arachidonic acid or ADP. Calcium-induced thromboxane B2 and nitric oxide production, LPS-induced prostaglandin E2 and nitric oxide production and LPS-induced interleukin 1β production were measured.
All compounds inhibited platelet aggregation, thromboxane B2 and inflammatory mediators in a concentration-dependent manner. The concentrations of each compound that inhibited the corresponding variable by 50 % compared to control samples (IC50) were in the range of 10−7–10−6 M for HT hexyl ether; for the other compounds, these values were in the range of 10−5 M. The IC50 for thromboxane B2 production was in the range of 10−4 M. The effects of HT alkyl ether derivatives were greater than those of HT. These compounds increased nitric oxide production. There was no direct relationship between the effects of these compounds and alkyl chain length. Maximum effects were observed in the C4–C6 range.
Alkyl ether derivatives of HT exert antiplatelet and anti-inflammatory effects that are greater than those of HT.
KeywordsHydroxytyrosol alkyl ether derivatives Platelet aggregation Prostanoids Nitric oxide Inflammatory mediators
This work was supported by Grants AGL7-66373-C04 AGL7-66373-C02 from the Programa Consolider-Ingenio (Spanish Ministry of Education and Science, CICYT). We thank K. Shashok for improving the use of English in the manuscript.
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