Search

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 the present study was to determine the role of the catechol group in the antioxidant and neuroprotective effects of minor components of virgin olive oil in rat brain tissue. Hydroxytyrosol ethyl ether (HT, 2 OH), tyrosol ethyl ether (Ty, 1 OH) and 3,4-di-ortho-methylidene-hydroxytyrosol ethyl ether (MET, no OH) were compared. Oxidative stress was induced with ferrous salts (lipid peroxidation induction), diethylmaleate (depletion of glutathione) and hypoxia-reoxygenation in brain slices. Lipid peroxidation was inhibited in direct proportion to the number of OH groups: HT>Ty>MET. Exposure to HT led to partial recovery of the glutathione system after chemical inhibition or hypoxia-reoxygenation. All three compounds inhibited cell death in hypoxia-reoxygenation experiments (HT≥Ty>MET). Peroxynitrite formation (3-nitrotyrosine) and inflammatory mediators (prostaglandin E2 and interleukin 1ß) were inhibited by all three compounds. In conclusion, the presence of OH groups in the molecule of these phenolic compounds from virgin olive oil is a determinant factor in their antioxidant effect in brain tissue, but this antioxidant effect is not the only explanation for their neuroprotective effect., (Copyright © 2015. Published by Elsevier Inc.)

The aim of the present study was to investigate the antioxidant and possible neuroprotective and antioxidant effects of five alkyl hydroxytyrosyl (HT) ethers (ethyl, butyl, hexyl, octyl and dodecyl) in rat brain slices. None of the compounds modified lipid peroxidation or glutathione concentrations (GSH) in oxygenated samples. The effects of oxidative stress were investigated with ferrous salts to induce lipid peroxidation and diethylmaleate (DEM) to reduce GSH. All compounds inhibited lipid peroxidation with an inhibitory concentration 50% (IC(50)) one tenth that of HT. These compounds, especially the butyl derivative, prevented GSH depletion after incubation with DEM. We also explored the neuroprotective effect of these compounds in an experimental model of hypoxia-reoxygenation in rat brain slices. All compounds showed neuroprotective and antioxidant effects. Our results established a relationship between these effects and the length of the carbon chain (maximum effect in the range of C4-C8)., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

This study was designed to determine whether the oral administration of hydroxytyrosol (HT) alkyl ether derivatives has a neuroprotective effect in rats. The animals were treated for 7 days with HT or ethyl, butyl, hexyl, octyl, and dodecyl HT ether. A method of in vitro hypoxia-reoxygenation in brain slices was used. Hexyl, octyl, and dodecyl HT derivatives reduced brain cell death (LDH efflux). Lipid peroxidation and nitrite concentrations were inhibited most by hexyl, octyl, and dodecyl derivatives. Concentrations of 3-nitrotyrosine were reduced by HT butyl, hexyl, octyl, and dodecyl ether derivatives. Interleukin-1β was significantly reduced in brain slices from rats treated with all HT ether derivatives. LDH efflux showed a linear correlation with brain concentrations of lipid peroxides, nitrites plus nitrates, and interleukin 1β. The reduction in oxidative and nitrosative stress and decreased production of pro-inflammatory interleukins may be the basis for the observed neuroprotective effects.

Hydroxytyrosol (HT) and hydroxytyrosol acetate (HT-AC) are two well-known phenolic compounds with antioxidant properties that are present in virgin olive oil (VOO). Because VOO has shown neuroprotective effects in rats, the purpose of the present study was to investigate the possible neuroprotective effect of HT and HT-AC in a model of hypoxia-reoxygenation in rat brain slices after in vitro incubation of these compounds or after 7 days of oral treatment with 5 or 10 mg/kg per day. Lactate dehydrogenase (LDH) efflux to the incubation medium was measured as a marker of brain cell death. HT and HT-AC inhibited LDH efflux in a concentration-dependent manner, with 50% inhibitory concentrations of 77.78 and 28.18 microM, respectively. Other well-known antioxidants such as vitamin E and N-acetyl-cysteine had no neuroprotective effect in this experimental model. After 1 week of treatment, HT (5 and 10 mg/kg per day p.o.) reduced LDH efflux by 37.8% and 52.7%, respectively, and HT-AC reduced LDH efflux by 45.4% and 67.8%. These data are additional evidence of the cytoprotective effect of VOO administration, and provide a preliminary basis for further study of these polyphenols as potential neuroprotective compounds.