Effects of hydroxytyrosol on some cardiovascular biomarkers in streptozotocin-diabetic rats

M Abdel-Karim1, A Guerrero2, JJ Reyes de la Vega1, JA Lopez-Villodres2, J Muñoz-Marin2, JA Gonzalez-Correa2, JP De la Cruz2. 1Faculty of Health Sciences. University of Malaga, Research Group LIAIT. Department of Pharmacology, Spain, 2School of Medicine, Research Group LIAIT. Department of Pharmacology, Spain

Introduction. The salutary effects of olive oil on many cardiovascular risk factors have been documented scientifically as beneficial for the lipid and thrombotic profile, insulin-mediated glucose metabolism, blood pressure, hemostasis, endothelial function, inflammation and oxidative stress. Although different components in virgin olive oil (VOO) such as oleic acid can show properties that benefit health, there is a general consensus that polyphenols are one of the components responsible for these benefits. The polyphenol present at highest concentrations in VOO is hydroxytyrosol (3,4-dihydroxyphenylethanol) (HT). The aim of the present study was to evaluate the effect of the oral administration of HT to two-month evolution diabetic rats on some biomarkers of vascular inflammation and platelet aggregation.

Material and Methods. The study was carried out on two-month evolution diabetic rats induced with streptozotocine. Seven groups of rats (N = 12 rats per group) were constituted: non diabetic rats (NDR), diabetic rats without treatment with HT (DR) and diabetic rats treated from the first day of diabetes (blood glucose >11.1 mmol/L) with HT (0.5, 1, 2.5, 5 and 10 mg/kg/day, respectively). HT was administered orally once a day. At the end of the experimental follow up, some variables were determined: maximum intensity of platelet aggregation in whole blood induced with collagen (Imax), plasma concentration of oxidized LDL (oxLDL), malondialdehyde (MDA), reduced and oxidized glutathione (GSH and GSSG), VCAM-1 and myeloperoxidase (MPO).

Results. None of the HT doses modified body weight or blood glucose concentration (p > 0.1). Collagen-induced platelet aggregation was higher in DR than in NDR (14.5±1.3 vs 28.3±1.4 ohms in DR, p<0.0001); HT reduced Imax in a dose-dependent manner (from 26.2±0.8 ohms with 0.5 mg/kg/day to 10.8±0.8 ohms with 10 mg/kg/day). Plasma MDA was higher in DR than in NDR (0.27±0.03 vs 0.6±0.05 nmol/mg prot, p < 0.0001); HT reduced MDA concentration with all the doses (p < 0.0001). Both GSH and GSSG were not modified with HT administration (p<0.1). oxLDL concentration was higher in DR than in NDR (13.1±1.3 vs 21.8±2.1 ng/mL, p < 0.0001); HT reduced oxLDL concentration with all the doses (p < 0.0001). VCAM-1 concentration was higher in DR than in NDR (0.3±0.03 vs 1.1±0.09 ng/mL, p < 0.0001); HT reduced VCAM-1 concentration with all the doses (45-55% inhibition p < 0.0001). MPO concentration was higher in DR than in NDR (4.1±0.2 vs 12.3±1.2 ng/mL, p < 0.0001); HT reduced MPO concentration with all the doses (43-74% inhibition p < 0.0001). There were statistical linear correlations between MDA and ox LDL (Pearson coefficient 0.525, p<0.0001) and VCAM-a (Pearson coefficient 0.444, p<0.0001).

Conclusions. Oral administration of HT prevents most of the altered cardiovascular biomarkers in two-month evolution diabetic rats. The antioxidant effect of HT could be related with oxLDL and VCAM-1 changes after HT administration.