Hydroxytyrosol and tyrosol sulfate metabolites protect against the oxidized cholesterol pro-oxidant effect in Caco-2 human enterocyte-like cells.
The aim of this study was to investigate the ability of the sulfate metabolites of hydroxytyrosol (HT) and tyrosol (TYR) to act as antioxidants counteracting the pro-oxidant effect of oxidized cholesterol in intestinal cells. For this purpose, we synthesized sulfate metabolites of HT and TYR using a chemical methodology and examined their antioxidant activity in Caco-2 monolayers in comparison with the parent compounds. Exposure to oxidized cholesterol led to ROS production, oxidative damage, as indicated by the MDA increase, a decrease of reduced glutathione concentration and an enhancement of glutathione peroxidase activity. All the tested compounds were able to counteract the oxidizing action of oxidized cholesterol; HT and TYR sulfate metabolites showed an efficiency in protecting intestinal cells comparable to that of the parent compounds, strengthening the assumption that the potential beneficial effect of the parent compounds is retained, although extensive metabolisation occurs, the resulting metabolites being able to exert a biological action themselves.
Dipartimento di Scienze Biomediche, Unità di Patologia Sperimentale, Università degli Studi di Cagliari, Cittadella Universitaria SS 554, 09042 Monserrato, Cagliari, Italy. mdeiana@unica.it.
Angela
A
Atzeri
Department of Bioorganic Chemistry, Instituto de Investigaciones Químicas, CSIC-Universidad de Sevilla, 49 Americo Vespucio, 41092 Sevilla, Spain.
Ricardo
R
Lucas
Dipartimento di Scienze Biomediche, Unità di Patologia Sperimentale, Università degli Studi di Cagliari, Cittadella Universitaria SS 554, 09042 Monserrato, Cagliari, Italy. mdeiana@unica.it.
Alessandra
A
Incani
Institute of Parasitology and Biomedicine López Neyra, Avenida del Conocimiento, 17, 18016 Armilla-Granada, Spain. jcmorales@ipb.csic.es.
Pablo
P
Peñalver
Department of Analytical Chemistry, Faculty of Sciences, University of Granada, C/Severo Ochoa, s/n, 18001 Granada, Spain.
Alberto
A
Zafra-Gómez
Dipartimento di Scienze Biomediche, Unità di Patologia Sperimentale, Università degli Studi di Cagliari, Cittadella Universitaria SS 554, 09042 Monserrato, Cagliari, Italy. mdeiana@unica.it.
M Paola
MP
Melis
Dipartimento di Medicina Molecolare, Università degli Studi di Pavia, Via Ferrata 9, 27100 Pavia, Italy.
Roberto
R
Pizzala
Department of Bioorganic Chemistry, Instituto de Investigaciones Químicas, CSIC-Universidad de Sevilla, 49 Americo Vespucio, 41092 Sevilla, Spain and Institute of Parasitology and Biomedicine López Neyra, Avenida del Conocimiento, 17, 18016 Armilla-Granada, Spain. jcmorales@ipb.csic.es.
Juan C
JC
Morales
Dipartimento di Scienze Biomediche, Unità di Patologia Sperimentale, Università degli Studi di Cagliari, Cittadella Universitaria SS 554, 09042 Monserrato, Cagliari, Italy. mdeiana@unica.it.
Monica
M
Deiana
D018938:Caco-2 Cells; D002784:Cholesterol / Q000737:chemistry / Q000633:toxicity*; D020895:Enterocytes / Q000187:drug effects*; D006801:Humans; D008315:Malondialdehyde; D015394:Molecular Structure; D016877:Oxidants / Q000633:toxicity; D010084:Oxidation-Reduction; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D013431:Sulfates / Q000737:chemistry / Q000378:metabolism
D016877:Oxidants; D013431:Sulfates; C005975:3,4-dihydroxyphenylethanol; C011867:4-hydroxyphenylethanol; D008315:Malondialdehyde; D002784:Cholesterol; D010626:Phenylethyl Alcohol