title: Alkyl hydroxytyrosyl ethers show protective effects against oxidative stress in HepG2 cells.
abstract: Alkyl hydroxytyrosyl ethers (methyl, ethyl, propyl, and butyl ethers) have been synthesized from hydroxytyrosol (HTy) in response to the increasing food industry demand of new lipophilic antioxidants. Having confirmed that these compounds reach portal blood partially unconjugated and thus are effectively absorbed, their potential antioxidant activity was evaluated in the human hepatocarcinoma cell line (HepG2). The effects of 0.5-10 μM alkyl hydroxytyrosyl ethers on HepG2 cell integrity and redox status were assessed as well as the protective effect against oxidative stress induced by tert-butylhydroperoxide (t-BOOH). Cell viability (Crystal violet) and cell proliferation (BrdU assay) were measured as markers of cell integrity, concentration of reduced glutathione (GSH), generation of reactive oxygen species (ROS), and activity of antioxidant enzymes glutathione peroxidase (GPx) and glutathione reductase (GR) as markers of redox status and determination of malondialdehyde (MDA) as a marker of lipid peroxidation. Direct treatment of HepG2 with alkyl hydroxytyrosyl ethers induced slight changes in cellular intrinsic antioxidants status, reducing ROS generation and inducing changes in GPx and GR activities. Pretreatment of HepG2 cells with alkyl hydroxytyrosyl ethers counteracted cell damage induced by t-BOOH, partially after 2 h and completely after 20 h, by increasing GSH and decreasing ROS generation, MDA levels, and antioxidant enzyme (GPx and GR) activity. According to these results the alkyl hydroxytyrosyl ethers show clear protective effects against oxidative stress, related to their lipophilic nature, that are similar to or even higher than those of their precursor, HTy.
authors.affiliation: IFAPA Centro Venta del Llano, Bailén-Motril, Km 18.5, E-23620 Mengíbar (Jaén), Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Pereira-Caro
authors.forename: Beatriz
authors.initials: B
authors.lastname: Sarriá
authors.forename: Andrés
authors.initials: A
authors.lastname: Madrona
authors.forename: José Luis
authors.initials: JL
authors.lastname: Espartero
authors.forename: Luis
authors.initials: L
authors.lastname: Goya
authors.forename: Laura
authors.initials: L
authors.lastname: Bravo
authors.forename: Raquel
authors.initials: R
authors.lastname: Mateos
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D004986:Ether / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D008315:Malondialdehyde / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D020011:Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D020011:Protective Agents; D017382:Reactive Oxygen Species; D004986:Ether; C005975:3,4-dihydroxyphenylethanol; D008315:Malondialdehyde; D010626:Phenylethyl Alcohol