title: Effect of the olive oil phenol hydroxytyrosol on human hepatoma HepG2 cells. Protection against oxidative stress induced by tert-butylhydroperoxide.
abstract: BACKGROUND
  Scientific evidence suggests that olive oil's beneficial effects are related to the high level of antioxidants, including phenolic compounds such as hydroxytyrosol. In vivo studies have shown that olive oil HTy is bioavailable and its biological activities, similar to those reported for other natural antioxidants such as quercetin, include prevention of LDL oxidation. Previous studies from our laboratory have shown that HTy and other phenolics in olive oil are absorbed and metabolized by cultured human hepatoma HepG2 cells where glucuronidated and methylated conjugates were the main derivatives formed, resembling the metabolic profile of olive oil phenols observed in human plasma and urine.
  
  
  OBJECTIVE
  The effect of olive oil phenol (HTy) on cell viability and redox status of cultured HepG2 cells, and the protective effect of HTy against an oxidative stress induced by tertbutylhydroperoxide (t-BOOH) were investigated.
  
  
  METHODS
  Lactate dehydrogenase activity as marker for cell integrity, concentration of reduced glutathione (GSH), generation of reactive oxygen species (ROS) and activity of the antioxidant enzyme glutathione peroxidase (GPx) as markers of redox status and determination of malondialdehyde (MDA) as marker of lipid peroxidation were measured.
  
  
  RESULTS
  No changes in cell integrity or intrinsic antioxidant status resulted from a direct treatment with 10-40 microM HTy. Pre-treatment of HepG2 with 10-40 microM HTy for 2 or 20 h completely prevented cell damage as well as the decrease of reduced glutathione and increase of malondialdehyde evoked by t-BOOH in HepG2 cells. Reactive oxygen species generation and the significant increase of glutathione peroxidase activity induced by t-BOOH were greatly reduced when cells were pretreated with HTy.
  
  
  CONCLUSIONS
  The results clearly show that treatment of HepG2 cells with the olive oil phenolic HTy may positively affect their antioxidant defense system, favoring cell integrity and resistance to cope with a stressful situation.
authors.affiliation: Depto. de Metabolismo y Nutrición, Instituto del Frío (CSIC), C/José Antonio Novais, 10 Ciudad Universitaria, 28040 Madrid, Spain. luisgoya@if.csic.es
authors.forename: Luis
authors.initials: L
authors.lastname: Goya
authors.forename: Raquel
authors.initials: R
authors.lastname: Mateos
authors.forename: Laura
authors.initials: L
authors.lastname: Bravo
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D001682:Biological Availability; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008113:Liver Neoplasms / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D000069463:Olive Oil; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D010938:Plant Oils / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D000069463:Olive Oil; D010938:Plant Oils; D017382:Reactive Oxygen Species; C005975:3,4-dihydroxyphenylethanol; D008315:Malondialdehyde; D020122:tert-Butylhydroperoxide; D007770:L-Lactate Dehydrogenase; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005978:Glutathione; D010626:Phenylethyl Alcohol