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-oxo-guanosine (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.