Decreased levels of advanced glycation end-products in patients with Gilbert syndrome

Oxidative stress plays an important role in the atherogenesis and bilirubin is one of the most potent antioxidant substances in human body. The aim of the present study was to investigate the impact of hyperbilirubinemia on plasma levels of advanced glycation end-products (AGEs), which contribute to atherogenesis. Two AGEs, pentosidine and N-epsilon-carboxymethyl lysine (CML), were determined in 23 subjects with Gilbert syndrome (GS) and in 21 age-matched healthy controls. Pentosidine was assessed by HPLC and CML was determined with ELISA. Logistic regression analysis was used for multiple adjustments of possible modifying factors. As expected, significantly higher serum bilirubin levels were found in GS subjects as compared to controls (28.9 +/- 9.6 vs 9.7 +/- 2.7 micromol/l, p < 0.001). In contrast, serum levels of both AGEs were significantly lower in GS compared to normobilirubinemic controls (median; 25%-75% interquartile range (pentosidine: 1.12; 0.90-1.28 vs 1.31; 1.18-1.58 nmol/g protein, p < 0.005; and CML: 6.70; 6.10-7.34 vs 7.33; 6.76-8.20 micromol/g protein, p = 0.01, respectively). Levels of both AGEs remained substantially lower even after adjustment for selected vascular risk and other modifying factors. In subjects with GS elevated serum bilirubin concentrations are associated with lower levels of AGEs. These results are in support of previous data on antioxidant properties of bilirubin.