title: Influence of quercetin and rutin on growth and antioxidant defense system of a human hepatoma cell line (HepG2).
abstract: BACKGROUND
  Dietary polyphenols like quercetin and rutin are considered beneficial because of their potential protective role in the pathogenesis of multiple diseases associated to oxidative stress such as cancer, coronary heart disease and atherosclerosis. However, many of these effects may depend on the concentration of the polyphenol utilized since high doses of some phenolic compounds may be prooxidant and negatively affect cell growth and viability.
  
  
  OBJECTIVE
  To test the potential chemoprotective effects of quercetin and rutin, two flavonols with high antioxidant capacity, on cell growth, viability and the response of the antioxidant defense system of a human hepatoma cell line (HepG2).
  
  
  METHODS
  Cell growth was measured by diaminobenzoic acid and bromodeoxyuridine assays, cell toxicity by lactate dehydrogenase leakage assay, reduced glutathione was quantified by a fluorimetric assay, cellular malondialdehyde was analyzed by high-performance liquid chromatography, reactive oxygen species were quantified by the dichlorofluorescein assay, antioxidant enzyme activities were determined by spectrophotometric analysis and their gene expression by northern blot.
  
  
  RESULTS
  Short-term exposure (4 h) to these flavonols had no antiproliferative nor cytotoxic effect. High doses of quercetin (50-100 microM) increased glutathione concentration and gene expression of Cu/Zn superoxide dismutase and catalase inhibiting the activity of the latter enzyme, whereas lower doses (0.1-1 microM) decreased gene expression of Cu/Zn superoxide dismutase and increased that of glutathione peroxidase. All doses of quercetin and rutin diminished reactive oxygen species and high doses (10-100 microM) decreased malondialdehyde concentration.
  
  
  CONCLUSIONS
  The results indicate that both natural antioxidants induce favorable changes in the antioxidant defense system of cultured HepG2 that prevent or delay conditions which favor cellular oxidative stress.
authors.affiliation: Depto. de Metabolismo y Nutrición, Instituto del Frío CSIC C/José Antonio Novais, 10. Ciudad Universitaria, 28040 Madrid, España, Spain.
authors.forename: Mario
authors.initials: M
authors.lastname: Alía
authors.forename: Raquel
authors.initials: R
authors.lastname: Mateos
authors.forename: Sonia
authors.initials: S
authors.lastname: Ramos
authors.forename: Elena
authors.initials: E
authors.lastname: Lecumberri
authors.forename: Laura
authors.initials: L
authors.lastname: Bravo
authors.forename: Luis
authors.initials: L
authors.lastname: Goya
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000097:blood / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D011794:Quercetin / Q000494:pharmacology* / Q000633:toxicity; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012431:Rutin / Q000494:pharmacology* / Q000633:toxicity; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
chemical_list: D000975:Antioxidants; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D012431:Rutin; D011794:Quercetin; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione