Abstract

Hydroxytyrosol (HT) is the component primarily responsible for the neuroprotective effect of extra virgin olive oil (EVOO). However, it is less effective on its own than the demonstrated neuroprotective effect of EVOO, and for this reason, it can be postulated that there is an interaction between several of the polyphenols of EVOO. The objective of the study was to assess the possible interaction of four EVOO polyphenols (HT, tyrosol, dihydroxyphenylglycol, and oleocanthal) in an experimental model of hypoxia-reoxygenation in rat brain slices. The lactate dehydrogenase (LDH) efflux, lipid peroxidation, and peroxynitrite production were determined as measures of cell death, oxidative stress, and nitrosative stress, respectively. First, the polyphenols were incubated with the brain slices in the same proportions that exist in EVOO, comparing their effects with those of HT. In all cases, the cytoprotective and antioxidant effects of the combination were greater than those of HT alone. Second, we calculated the concentration–effect curves for HT in the absence or presence of each polyphenol. Tyrosol did not significantly modify any of the variables inhibited by HT. Dihydroxyphenylglycol only increased the cytoprotective effect of HT at 10 µM, while it increased its antioxidant effect at 50 and 100 µM and its inhibitory effect on peroxynitrite formation at all the concentrations tested. Oleocanthal increased the cytoprotective and antioxidant effects of HT but did not modify its inhibitory effect on nitrosative stress. The results of this study show that the EVOO polyphenols DHPG and OLC increase the cytoprotective effect of HT in an experimental model of hypoxia-reoxygenation in rat brain slices, mainly due to a possibly synergistic effect on HT’s antioxidant action. These results could explain the greater neuroprotective effect of EVOO than of the polyphenols alone.

Highlights

  • The beneficial effect of the intake of extra virgin olive oil (EVOO) for the prevention of cardiovascular diseases has been widely demonstrated [1]

  • We carried out hypoxia-reoxygenation experiments in rat brain sections, incubating with the four polyphenol compounds according to their reported concentrations in EVOO, according to high, medium, or low EVOO polyphenol contents, and compared the results with those for HT alone at the same concentration

  • The cytoprotective and antioxidant effects of the mixture of HT, Ty, DHPG, and OLC were significantly greater than those of HT alone, by 30–50%, except for 3-NTy, which was inhibited to the same extent by HT as by the mixture of polyphenols

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Summary

Introduction

The beneficial effect of the intake of extra virgin olive oil (EVOO) for the prevention of cardiovascular diseases has been widely demonstrated [1]. High adherence to a Mediterranean diet model supplemented with approximately 50 mL of EVOO per day has been shown to reduce the incidence of coronary ischemic attacks, peripheral artery disease, and ischemic stroke, in addition to preventing the onset of obesity and type 2 diabetes [1,2]. Different chemical components of EVOO have been studied separately, and the cardioprotective and neuroprotective effects of EVOO have been attributed to the polyphenol most abundant in its composition, hydroxytyrosol (HT), [5]. These effects are explained by the antioxidant effect demonstrated for HT in various tissues and in experimental models of disease, such as diabetes, hypertension, and dyslipidemia [6,7]

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