Proceedings of The Physiological Society

University of Cambridge (2008) Proc Physiol Soc 11, PC129

Poster Communications

Oleuropein and cycloolivil from olive tree wood exert antiaggregant effects in platelets from patients with type 2 diabetes mellitus

G. M. Salido1, H. Zibidi2, S. Salido3, J. Altarejos3, A. Bartegi2, J. A. Rosado1

1. Physiology, University of Extremadura, Caceres, Spain. 2. Unité de Recherche de Biochimie, Institut Supérieur de Biotechnologie, Monastir, Tunisia. 3. Department of Inorganic and Organic Chemistry, University of Jaen, Jaen, Spain.

Type 2 diabetes mellitus induces a number of cardiovascular disorders, including platelet hyperactivity and hyperaggregability, which are associated to an increased oxidant production and abnormal cytosolic Ca2+ handling (Redondo et al., 2005). Phenolic compounds have been reported to modulate several biological processes in platelets, such as cytosolic free Ca2+ concentration, endogenous reactive oxygen species generation, protein tyrosine phosphorylation and aggregation (Ben Amor et al., 2007). In the present study, we have investigated the effect of two phenolic compounds obtained from the olive tree, oleuropein and cycloolivil, on Ca2+ mobilization, protein tyrosine phosphorylation and aggregation in platelets from type 2 diabetic and healthy donors. Blood was drawn from volunteers with local ethical committee approval. Cytosolic free Ca2+ concentration ([Ca2+]i) measurement, Western blotting and platelet aggregation were performed as previously described (Bouaziz et al., 2007). Pretreatment of platelets with 100 µM oleuropein or cycloolivil reduced Ca2+ release and Ca2+ entry induced by the physiological agonist thrombin (1 U/mL) or by treatment with the SERCA inhibitor thapsigargin (1 µM) in combination with a low concentration of ionomycin (50 nM) in platelets from diabetic donors. As a result, in the presence of oleuropein or cycloolivil Ca2+ mobilisation was similar in platelets from healthy and diabetic subjects. In addition, oleuropein and cycloolivil reduced thrombin-induced aggregation in platelets from type 2 diabetic subjects and controls in a concentration-dependent manner. The effect of oleuropein and cycloolivil at the concentration 100 µM on platelet aggregation was comparable to that induced by 100 µM hydroxytyrosol, a well known oxygen radical scavenger. Finally, both oleuropein and cycloolivil significantly reduced thrombin-evoked protein tyrosine phosphorylation in platelets from diabetic donors and controls. We conclude that oleuropein and cycloolivil exert an effective antiaggregant effect in platelets from patients with type 2 diabetes mellitus and reverses the enhanced Ca2+ mobilization and hyperaggregability described for this pathology.

Where applicable, experiments conform with Society ethical requirements