Effects of hydroxytyrosol on cardiovascular and neuroprotective biomarkers in experimental diabetes mellitus

The aim of this study was to assess the influence of hydroxytyrosol (HT) on cardiovascular inflammation and neuroprotective effect in streptozotocin‐diabetic rats. Four groups of rats (N=10 per group) were studied for 2 months: nondiabetic rats (NDR), diabetic rats treated with saline (DR) and DR treated with HT (1, and 5 mg/kg/day p.o.). At the end of follow‐up an experimental model of hypoxia‐reoxygenation in brain slices was tested. Vascular variables: DR had higher platelet aggregation values, higher thromboxane B 2 , plasma lipid peroxidation, 3‐nitrotyrosine, oxidized LDL (oxLDL), myeloperoxidase, vascular cell adhesion molecule 1 (VCAM‐1) and interleukin‐1β (IL‐1β) concentrations, and lower aortic 6‐keto‐prostaglandin F 1α and nitric oxide production than NDR. Aortic wall area and smooth muscle cell count were also higher in DR than in NDR. Brain variables: the DR group showed increased cell death, oxidative and nitrosative stress and an increase in brain inflammatory mediators. HT significantly reduced both oxidative and nitrosative stress, oxLDL concentration (35% and 40% of reduction respect untreated animals for 1 or 5 mg/kg/day respectively), VCAM‐1 (63% and 50%), platelet aggregation (22% and 40%) and thromboxane B 2 production (22% and 25%). Morphometric values in the aortic wall were reduced to values near those in NDR. Respect the brain variables the result obtained were the following: HT significantly reduced oxidative lipid peroxidation (38% and 52 of reduction respect untreated animals for 1 or 5 mg/kg/day respectively) and nitrosative stress (47% and 50%) and peroxynitrite concentration (43% and 60%) and brain inflammatory mediators (19–30% prostaglandin E 2 and 16–50% interleukin 1β concentration). Cell death was reduced by 26% and 38% after the administration of 1 or 5 mg/kg/day. In conclusion, HT influenced the major biochemical processes leading to diabetic vasculopathy, reduced cell proliferation in the vascular wall and had a neuroprotective effect in this experimental model.