title: Quercetin protects human-derived liver cells against mercury-induced DNA-damage and alterations of the redox status.
abstract: Aim of this study was to investigate the cytotoxic and genotoxic properties of inorganic and organic mercury compounds, i.e., HgCl(2) and methylmercury (MeHg). In addition, the DNA-protective and antioxidant effects of the flavonoid quercetin (QC) were studied. All experiments were conducted with human-derived liver cells (HepG2), which possess antioxidant and drug-metabolizing enzymes in an inducible form. 8-Hydroxydeoxyguanosine (8-OHdG) and comet formation were monitored as endpoints of DNA damage. The impact of the metal compounds on the redox status was also investigated, since it is assumed that their toxic effects are due to oxidative damage. A number of biochemical parameters related to oxidative stress, namely glutathione, malondialdehyde, protein carbonyl and formation of reactive oxygen species (ROS) were measured after treatment of the cells with the mercury compounds in the presence and absence of quercetin. To elucidate the mechanisms that underlie the effects of QC, three protocols (pre-, simultaneous and post-treatment) were used. Both mercury compounds (range 0.1-5.0μM) caused induction of DNA migration and formation of 8-OHdG. In combination with the flavonoid (range 0.1-5.0μM), DNA-protective effects of QC were observed after pre- and simultaneous treatment but not when the flavonoid was added after treatment with the metal compounds. Exposure to the metal compounds led also to substantial changes of all parameters of the redox status and co-treatment experiments with QC showed that these alterations are reversed by the flavonoid. Taken together, the results of our experiments indicate that these two mercury compounds cause DNA damage and oxidative stress in human-derived liver cells and that the flavonoid reduces these effects. Since the concentrations of the metals and of the flavonoids used in the present work reflect human exposure, our findings can be taken as an indication that QC may protect humans against the adverse effects caused by the metal.
authors.affiliation: Departamento de Análises Clínicas, Bromatológicas e Toxicológicas, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Gustavo Rafael Mazzaron
authors.initials: GR
authors.lastname: Barcelos
authors.forename: José Pedro Friedmann
authors.initials: JP
authors.lastname: Angeli
authors.forename: Juliana Mara
authors.initials: JM
authors.lastname: Serpeloni
authors.forename: Denise
authors.initials: D
authors.lastname: Grotto
authors.forename: Bruno Alves
authors.initials: BA
authors.lastname: Rocha
authors.forename: Jairo Kenupp
authors.initials: JK
authors.lastname: Bastos
authors.forename: Siegfried
authors.initials: S
authors.lastname: Knasmüller
authors.forename: Fernando Barbosa
authors.initials: FB
authors.lastname: Júnior
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D016587:Antimutagenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002470:Cell Survival; D004249:DNA Damage / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D056945:Hep G2 Cells; D006801:Humans; D008627:Mercuric Chloride / Q000633:toxicity*; D008767:Methylmercury Compounds / Q000633:toxicity*; D010084:Oxidation-Reduction / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D011794:Quercetin / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016587:Antimutagenic Agents; D000975:Antioxidants; D008767:Methylmercury Compounds; D017382:Reactive Oxygen Species; D008627:Mercuric Chloride; D000080242:8-Hydroxy-2'-Deoxyguanosine; D011794:Quercetin; D003849:Deoxyguanosine