title: Hydroxytyrosyl alkyl ether derivatives inhibit platelet activation after oral administration to rats.
abstract: 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 B2 (TxB2), aortic 6-keto-prostaglandin F1α (6-keto-PGF1α) 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, TxB2 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-PGF1α 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.
authors: Laboratorio de Investigaciones Antitrombóticas e Isquemia Tisular (LIAIT), Department of Pharmacology and Therapeutics, School of Medicine, University of Málaga, 29071 Málaga, Spain.
authors: Javier
authors: J
authors: Muñoz-Marín
authors: José Pedro
authors: JP
authors: De la Cruz
authors: José Julio
authors: JJ
authors: Reyes
authors: Juan Antonio
authors: JA
authors: López-Villodres
authors: Ana
authors: A
authors: Guerrero
authors: Inmaculada
authors: I
authors: López-Leiva
authors: José Luis
authors: JL
authors: Espartero
authors: María Teresa
authors: MT
authors: Labajos
authors: José Antonio
authors: JA
authors: González-Correa
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004987:Ethers / Q000494:pharmacology*; D008297:Male; D015539:Platelet Activation / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004987:Ethers
keywords: Hydroxytyrosol ethers; Non-linear effect; Olive oil polyphenols; Platelet aggregation; Prostanoids