title: Hyperbilirubinemia, augmentation of endothelial function, and decrease in oxidative stress in Gilbert syndrome.
abstract: BACKGROUND
  Patients with Gilbert syndrome have mild unconjugated hyperbilirubinemia. It has been shown that bilirubin is an endogenous antioxidant. We evaluated the role of oxidative stress in endothelial function in patients with Gilbert syndrome under normal conditions without cardiovascular risk factors.
  
  
  RESULTS
  A total of 108 young men with Gilbert syndrome without cardiovascular risk factors and 108 age-matched healthy men (normal controls) were enrolled in this study. Serum concentrations of bilirubin were higher in patients with Gilbert syndrome than in control subjects (29.2±11.6 versus 9.4±2.7 μmol/L; P<0.001). Serum concentrations of malondialdehyde-modified low-density lipoprotein and urinary excretion of 8-hydroxy-2'-deoxyguanosine (8-OHdG), as indices of oxidative stress, were lower in patients with Gilbert syndrome than in control subjects (61.8±24.5 versus 72.5±21.8 U/L, P=0.034; 7.8±2.4 versus 10.4±3.2 ng/mg creatinine, P=0.001, respectively). Flow-mediated vasodilation was greater in patients with Gilbert syndrome than in normal control subjects (7.2±2.2% versus 5.9±1.7%; P<0.001). Vascular responses to nitroglycerine were not significantly different between the 2 groups. Flow-mediated vasodilation correlated with serum concentration of bilirubin (r=0.44, P<0.001), malondialdehyde-modified low-density lipoprotein (r=-0.25, P=0.01), and urinary excretion of 8-OHdG (r=-0.27, P=0.004) in patients with Gilbert syndrome but not in control subjects. In addition, serum concentration of bilirubin correlated with malondialdehyde-modified low-density lipoprotein (r=-0.20, P=0.04) and 8-OHdG (r=-0.21, P=0.02) in patients with Gilbert syndrome but not in control subjects.
  
  
  CONCLUSIONS
  Patients with Gilbert syndrome had low levels of oxidative stress associated with hyperbilirubinemia and enhancement of endothelium-dependent vasodilation.
  
  
  BACKGROUND
  URL: http://www.umin.ac.jp. Unique identifier: UMIN000003409.
authors: Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
authors: Tatsuya
authors: T
authors: Maruhashi
authors: Junko
authors: J
authors: Soga
authors: Noritaka
authors: N
authors: Fujimura
authors: Naomi
authors: N
authors: Idei
authors: Shinsuke
authors: S
authors: Mikami
authors: Yumiko
authors: Y
authors: Iwamoto
authors: Masato
authors: M
authors: Kajikawa
authors: Takeshi
authors: T
authors: Matsumoto
authors: Yasuki
authors: Y
authors: Kihara
authors: Kazuaki
authors: K
authors: Chayama
authors: Kensuke
authors: K
authors: Noma
authors: Ayumu
authors: A
authors: Nakashima
authors: Hirofumi
authors: H
authors: Tomiyama
authors: Bonpei
authors: B
authors: Takase
authors: Akira
authors: A
authors: Yamashina
authors: Yukihito
authors: Y
authors: Higashi
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D001663:Bilirubin / Q000097:blood; D001916:Brachial Artery / Q000502:physiology; D016022:Case-Control Studies; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D004730:Endothelium, Vascular / Q000502:physiology*; D005878:Gilbert Disease / Q000097:blood* / Q000503:physiopathology*; D006801:Humans; D006932:Hyperbilirubinemia / Q000097:blood / Q000503:physiopathology*; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology*; D012039:Regional Blood Flow / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D008077:Lipoproteins, LDL; D000080242:8-Hydroxy-2'-Deoxyguanosine; D005996:Nitroglycerin; D003849:Deoxyguanosine; D001663:Bilirubin