About: Anti-Genotoxic Potential of Bilirubin In Vivo: Damage to DNA in Hyperbilirubinemic Human and Animal Models     Goto   Sponge   NotDistinct   Permalink

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  • The bile pigment bilirubin is a known antioxidant and is associated with protection from cancer and cardiovascular disease (CVD) when present in too strong concentrations. Unconjugated bilirubin (UCB) might also possess anti-genotoxic potential by preventing oxidative damage to DNA. Moderately elevated bilirubin levels are found in individuals with Gilbert syndrome and more severe in the hyperbilirubinemic Gunn rat model. This study was therefore aimed to assess the levels of oxidative damage to DNA in Gilbert syndrome subjects and Gunn rats compared tomatched controls. Seventy-six individuals (age- and sex-matched) were allocated into Gilbert syndrome (UCB }= 17.1 mu mol/L; n - 38) or control groups (UCB < 17.1 mu mol/L; n = 38). In addition, 40 Gunn rats were used to support the results of the human trial. Single-cell gel electrophoresis (SCGE) assay measuring standard conditions (strand breaks, apurinic/apyrimidinic sites) and formamidopyrimidine glycosylase (FPG)-sensitive sites was conducted in human peripheral blood mononuclear cells (PBMC) and rat PBMCs, colon, and hepatocytes. Furthermore, urinary 8-oxo-2'-deoxyguanosine (8oxodGuo, DNA oxidation) and 8-oxoguanosine (8oxoGuo, RNA oxidation) were measured in humans. The Gilbert syndrome and Gunn rat groups had significantly higher UCB levels (P < 0.001) than the corresponding controls. No further differences in damage to DNA or RNA were detected between the two groups, except higher strand breaks (PBMCs) in Gunn rats when compared with controls. However, when demographic effects were analyzed, lower 8oxodGuo concentrations were detected in the human group with a BMI }= 25 kg/m(2) (1.70 +/- 0.67 vs. 1.38 +/- 0.43 nmol/mmol creatinine, P < 0.05), although this group showed lower UCB levels than normal weight subjects. This study suggests that the disease preventative effect of UCB is unrelated to DNA oxidation/strand breaks in human and animal models of hyperbilirubinaemia. (c)2013 AACR.
  • The bile pigment bilirubin is a known antioxidant and is associated with protection from cancer and cardiovascular disease (CVD) when present in too strong concentrations. Unconjugated bilirubin (UCB) might also possess anti-genotoxic potential by preventing oxidative damage to DNA. Moderately elevated bilirubin levels are found in individuals with Gilbert syndrome and more severe in the hyperbilirubinemic Gunn rat model. This study was therefore aimed to assess the levels of oxidative damage to DNA in Gilbert syndrome subjects and Gunn rats compared tomatched controls. Seventy-six individuals (age- and sex-matched) were allocated into Gilbert syndrome (UCB }= 17.1 mu mol/L; n - 38) or control groups (UCB < 17.1 mu mol/L; n = 38). In addition, 40 Gunn rats were used to support the results of the human trial. Single-cell gel electrophoresis (SCGE) assay measuring standard conditions (strand breaks, apurinic/apyrimidinic sites) and formamidopyrimidine glycosylase (FPG)-sensitive sites was conducted in human peripheral blood mononuclear cells (PBMC) and rat PBMCs, colon, and hepatocytes. Furthermore, urinary 8-oxo-2'-deoxyguanosine (8oxodGuo, DNA oxidation) and 8-oxoguanosine (8oxoGuo, RNA oxidation) were measured in humans. The Gilbert syndrome and Gunn rat groups had significantly higher UCB levels (P < 0.001) than the corresponding controls. No further differences in damage to DNA or RNA were detected between the two groups, except higher strand breaks (PBMCs) in Gunn rats when compared with controls. However, when demographic effects were analyzed, lower 8oxodGuo concentrations were detected in the human group with a BMI }= 25 kg/m(2) (1.70 +/- 0.67 vs. 1.38 +/- 0.43 nmol/mmol creatinine, P < 0.05), although this group showed lower UCB levels than normal weight subjects. This study suggests that the disease preventative effect of UCB is unrelated to DNA oxidation/strand breaks in human and animal models of hyperbilirubinaemia. (c)2013 AACR. (en)
Title
  • Anti-Genotoxic Potential of Bilirubin In Vivo: Damage to DNA in Hyperbilirubinemic Human and Animal Models
  • Anti-Genotoxic Potential of Bilirubin In Vivo: Damage to DNA in Hyperbilirubinemic Human and Animal Models (en)
skos:prefLabel
  • Anti-Genotoxic Potential of Bilirubin In Vivo: Damage to DNA in Hyperbilirubinemic Human and Animal Models
  • Anti-Genotoxic Potential of Bilirubin In Vivo: Damage to DNA in Hyperbilirubinemic Human and Animal Models (en)
skos:notation
  • RIV/00216208:11110/13:10192311!RIV14-MSM-11110___
http://linked.open...avai/predkladatel
http://linked.open...avai/riv/aktivita
http://linked.open...avai/riv/aktivity
  • N
http://linked.open...iv/cisloPeriodika
  • 10
http://linked.open...vai/riv/dodaniDat
http://linked.open...aciTvurceVysledku
http://linked.open.../riv/druhVysledku
http://linked.open...iv/duvernostUdaju
http://linked.open...titaPredkladatele
http://linked.open...dnocenehoVysledku
  • 61405
http://linked.open...ai/riv/idVysledku
  • RIV/00216208:11110/13:10192311
http://linked.open...riv/jazykVysledku
http://linked.open.../riv/klicovaSlova
  • population; individuals; strand breaks; metabolic-rate; colorectal-cancer; cardiovascular protection; comet assay; serum bilirubin; oxidative stress; Gilberts syndrome (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • US - Spojené státy americké
http://linked.open...ontrolniKodProRIV
  • [50C265FE1219]
http://linked.open...i/riv/nazevZdroje
  • Cancer Prevention Research
http://linked.open...in/vavai/riv/obor
http://linked.open...ichTvurcuVysledku
http://linked.open...cetTvurcuVysledku
http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 6
http://linked.open...iv/tvurceVysledku
  • Vítek, Libor
  • Antl, Nadja
  • Bulmer, Andrew C.
  • Doberer, Daniel
  • Ferk, Franziska
  • Knasmueller, Siegfried
  • Marculescu, Rodrig
  • Moelzer, Christine
  • Muellner, Elisabeth
  • Najafi, Khatereh
  • Poulsen, Henrik E.
  • Rittmannsberger, Barbara
  • Schreidl, Stephanie
  • Wagner, Karl-Heinz
  • Wallner, Marlies
http://linked.open...ain/vavai/riv/wos
  • 000325272400007
issn
  • 1940-6207
number of pages
http://bibframe.org/vocab/doi
  • 10.1158/1940-6207.CAPR-13-0125
http://localhost/t...ganizacniJednotka
  • 11110
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