Anti-genotoxic potential of bilirubin in vivo

Autor(en)

M. Wallner, N. Antl, B. Rittmannsberger, S. Schreidl, K. Najafi, E. Müllner, C. Mölzer, Franziska Ferk, Siegfried Knasmüller, Rodrig Marculescu, D. Doberer, H.E. Poulsen, L. Vitek, A.C. Bulmer, Karl-Heinz Wagner

Abstrakt

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 to matched controls. Seventy-six individuals (age- and sex-matched) were allocated into Gilbert syndrome (UCB ≥17.1 μmol/L; n = 38) or control groups (UCB <17.1 μmol/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 (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.

Organisation(en)

Department für Ernährungswissenschaften

Externe Organisation(en)

Medizinische Universität Wien, Copenhagen University Hospital, Griffith University, Charles University Prague, Rigshospitalet, University of Copenhagen

Journal

Cancer Prevention Research

Band

6

Seiten

1056-1063

Anzahl der Seiten

8

ISSN

1940-6207

DOI

https://doi.org/10.1158/1940-6207.CAPR-13-0125

Publikationsdatum

10-2013

Peer-reviewed

Ja

ÖFOS 2012

303009 Ernährungswissenschaften, 301904 Krebsforschung

Sustainable Development Goals

SDG 3 – Gesundheit und Wohlergehen

Link zum Portal

https://ucrisportal.univie.ac.at/de/publications/antigenotoxic-potential-of-bilirubin-in-vivo(358d694e-b193-4ffe-bc44-91115da952f3).html