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The aim of the study was to test the neuroprotective effect of hydroxytyrosol (HT) on experimental diabetic retinopathy. Animals were divided in four groups: (1) control nondiabetic rats, (2) streptozotocin-diabetic rats (DR), (3) DR treated with 1 mg/kg/day p.o. HT, and (4) DR treated with 5 mg/kg/day p.o. HT. Treatment with HT was started 7 days before inducing diabetes and was maintained for 2 months. In the DR group, total area occupied by extracellular matrix was increased, area occupied by retinal cells was decreased; both returned to near-control values in DR rats treated with HT. The number of retinal ganglion cells in DR was significantly lower (44%) than in the control group, and this decrease was smaller after HT treatment (34% and 9.1%). Linear regression analysis showed that prostacyclin, platelet aggregation, peroxynitrites, and the dose of 5 mg/kg/day HT significantly influenced retinal ganglion cell count. In conclusion, HT exerted a neuroprotective effect on diabetic retinopathy, and this effect correlated significantly with changes in some cardiovascular biomarkers.

The aim of the study was to analyze the possible neuroprotective effect of hydroxytyrosol (HT) in diabetic animals in a model of hypoxia-reoxygenation. Rats (10 animals/group) were distributed in five groups: nondiabetic rats, control diabetic rats (DR), and DR rats treated for 2 months with 1, 5, or 10 mg/kg/day po HT. At the end of follow-up, an experimental model of hypoxia-reoxygenation in brain slices was tested. The DR group showed increased cell death, oxidative and nitrosative stress, and an increase in brain inflammatory mediators. These alterations were significantly greater in DR than in normoglycemic animals. HT significantly reduced oxidative (38.5-52.4% lipid peroxidation) and nitrosative stress (48.0-51.0% nitric oxide and 43.9-75.2% peroxynitrite concentration) and brain inflammatory mediators (18.6-40.6% prostaglandin E 2 and 17.0-65.0% interleukin 1β concentration). Cell death was reduced by 25.9, 37.5, and 41.0% after the administration of 1, 5, or 10 mg/kg/day. The administration of HT in rats with experimental diabetes thus had a neuroprotective effect.

The aim of this study was to assess the influence of hydroxytyrosol (HT) on cardiovascular biomarkers and morphometric parameters of the arterial wall in streptozotocin-diabetic rats. Seven 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 (0.5, 1, 2.5, 5 and 10 mg kg -1 day -1 p.o.). 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. HT significantly reduced both oxidative and nitrosative stress, oxLDL concentration, VCAM-1 and inflammatory mediators, platelet aggregation and thromboxane B 2 production. Morphometric values in the aortic wall were reduced to values near those in NDR. In conclusion, HT influenced the major biochemical processes leading to diabetic vasculopathy, and reduced cell proliferation in the vascular wall in this experimental model., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The neuroprotective effect of virgin olive oil (VOO) polyphenols has been related to their antioxidant effect. The main objective was to analyze how tyrosol and hydroxytyrosol contribute to the antioxidant and neuroprotective effects of VOO in a model of hypoxia-reoxygenation in rat brain slices. Rats were treated per os (po) (10 or 20 mg/kg/day) with hydroxytyrosol ethyl ether (HTEE), tyrosol ethyl ether (TEE), or 3,4-di-o-methylidene-hydroxytyrosol ethyl ether (MHTEE), used as a negative control for antioxidant effects. Lipid peroxidation was inhibited with HTEE, TEE, and MHTEE (from 5.0 ± 1.5 to 2.6 ± 1.5, 4.5 ± 1.5, and 4.8 ± 1.5 nmol/mg protein, respectively). However, all three compounds had similar neuroprotective effects: from 2.8 ± 0.07 to 1.8 ± 0.02 arbitrary units for HTEE, 1.4 ± 0.09 arbitrary units for TEE, and 1.3 ± 0.2 arbitrary units for MHTEE. All three compounds inhibited 3-nitrotyrosine production (from 3.7 ± 0.3 to 1.2 ± 0.03 nmol/0.1 g tissue for HTEE, 1.0 ± 0.2 nmol/0.1 g tissue for TEE, and 1.3 ± 0.1 nmol/0.1 g tissue for MHTEE), prostaglandin E2 production (from 55.7 ± 2.2 to 46.4 ± 1.9 pg/0.1 g tissue for HTEE, 24.7 ± 1.3 pg/0.1 g tissue for TEE, and 27.6 ± 2.6 pg/0.1 g tissue for MHTEE), whereas only HTEE inhibited IL1β production (from 35.7 ± 1.5 to 21.6 ± 0.8 pg/0.1 g tissue). Pearson correlation coefficients related neuroprotective effect with an antioxidant effect for HTEE (R = 0.72, p < 0.001), and inhibition of nitrosative stress (R = 0.78, 0.67, and 0.66 for HTEE, TEE, and MHTEE, respectively, p < 0.001) and inflammatory mediators (R = 0.72, 0.79, and 0.64 for HTEE, TEE, and MHTEE, respectively, p < 0.001) with all three compounds.

The aim of this study was to analyze the mechanism of the neuroprotective effect of hydroxytyrosol (HT) in an experimental model of hypoxia-reoxygenation in rat brain slices. After reoxygenation the increase in lactate dehydrogenase efflux was inhibited by HT in a concentration-dependent manner and dose-dependent inhibition after oral administration to rats for 7 days (1, 5 and 10 mg/kg per day). Maximum inhibition was 57.4% in vitro and 38.7% ex vivo. Hydroxytyrosol reduced oxidative stress parameters: it inhibited lipid peroxidation and increased enzymatic activities related with the glutathione system both in vitro and after oral administration to rats. The increase in prostaglandin E2 and interleukin 1β after reoxygenation were inhibited after incubation of brain slices with HT and after oral administration. The accumulation of nitric oxide in brain slices was reduced in a concentration-dependent manner. In conclusion, HT exerts a neuroprotective effect in a model of hypoxia-reoxygenation in rat brain slices, both in vitro and after 7 days of oral administration to rats. HT exerts an antioxidant activity and lowered some inflammatory markers in this model., (© 2013.)

Purpose: 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., Methods: 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 B(2) and nitric oxide production, LPS-induced prostaglandin E(2) and nitric oxide production and LPS-induced interleukin 1β production were measured., Results: All compounds inhibited platelet aggregation, thromboxane B(2) and inflammatory mediators in a concentration-dependent manner. The concentrations of each compound that inhibited the corresponding variable by 50 % compared to control samples (IC(50)) 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 IC(50) for thromboxane B(2) 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., Conclusions: Alkyl ether derivatives of HT exert antiplatelet and anti-inflammatory effects that are greater than those of HT.