De La Cruz Cortés, José PedroPérez de Algaba, InmaculadaMartín-Aurioles, EstherArrebola, María MonsaludOrtega-Hombrados, LauraRodríguez-Pérez, María DoloresFernández-Prior, María ÁfricaBermúdez-Oria, AlejandraVerdugo, CristinaGonzález-Correa, José Antonio2022-07-252022-07-252021-08-26De La Cruz Cortés JP, Pérez de Algaba I, Martín-Aurioles E, Arrebola MM, Ortega-Hombrados L, Rodríguez-Pérez MD, et al. Extra Virgin Oil Polyphenols Improve the Protective Effects of Hydroxytyrosol in an In Vitro Model of Hypoxia-Reoxygenation of Rat Brain. Brain Sci. 2021 Aug 26;11(9):1133http://hdl.handle.net/10668/3815Hydroxytyrosol (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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/HydroxytyrosolExtra virgin olive oilPolyphenolsIn vitroNeuroprotectionAceite de olivaPolifenolesNeuroprotecciónMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::RatsMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::AntioxidantsMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Benzene Derivatives::Phenols::PolyphenolsMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Benzene Derivatives::Phenols::Catechols::3-Methoxy-4-hydroxyphenylethanolMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Protective Agents::Neuroprotective AgentsMedical Subject Headings::Chemicals and Drugs::Inorganic Chemicals::Nitrogen Compounds::Nitrous Acid::Peroxynitrous AcidMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::BrainMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Deathresearch article34573155open access10.3390/brainsci110911332076-3425PMC8471209