Reduced circulating oxidized LDL is associated with hypocholesterolemia and enhanced thiol status in Gilbert syndrome

Boon, Ai-Ching, Hawkins, Clare L., Bisht, Kavita, Coombes, Jeff S., Bakrania, Bhavisha, Wagner, Karl-Heinz and Bulmer, Andrew C. (2012) Reduced circulating oxidized LDL is associated with hypocholesterolemia and enhanced thiol status in Gilbert syndrome. Free Radical Biology and Medicine, 52 10: 2120-2127. doi:10.1016/j.freeradbiomed.2012.03.002

Author Boon, Ai-Ching
Hawkins, Clare L.
Bisht, Kavita
Coombes, Jeff S.
Bakrania, Bhavisha
Wagner, Karl-Heinz
Bulmer, Andrew C.
Title Reduced circulating oxidized LDL is associated with hypocholesterolemia and enhanced thiol status in Gilbert syndrome
Journal name Free Radical Biology and Medicine   Check publisher's open access policy
ISSN 0891-5849
Publication date 2012-05
Sub-type Article (original research)
DOI 10.1016/j.freeradbiomed.2012.03.002
Volume 52
Issue 10
Start page 2120
End page 2127
Total pages 8
Place of publication Philadelphia, PA, United States
Publisher Elsevier
Collection year 2013
Language eng
Abstract A protective association between bilirubin and atherosclerosis/ischemic heart disease clearly exists in vivo. However, the relationship between bilirubin and in vivo oxidative stress parameters in a clinical population remains poorly described. The aim of this study was to assess whether persons expressing Gilbert syndrome (GS; i.e., unconjugated hyperbilirubinemia) are protected from thiol oxidation and to determine if this, in addition to their improved lipoprotein profile, could explain reduced oxidized low-density lipoprotein (oxLDL) status in them. Forty-four matched GS and control subjects were recruited and blood was prepared for the analysis of lipid profile and multiple plasma antioxidants and measures of oxidative stress. GS subjects possessed elevated plasma reduced thiol (8.03±1.09 versus 6.75±1.39 nmol/mg protein; P<0.01) and glutathione concentrations (12.7±2.39 versus 9.44±2.45 μM; P<0.001). Oxidative stress status (reduced:oxidized glutathione; GSH:GSSG) was significantly improved in GS (0.49±0.16 versus 0.32±0.12; P<0.001). Protein carbonyl concentrations were negatively associated with bilirubin concentrations and were significantly lower in persons with >40 μM bilirubin versus controls (<17.1 μmol/L; P<0.05). Furthermore, absolute oxLDL concentrations were significantly lower in GS subjects (P<0.05). Forward stepwise regression analysis revealed that bilirubin was associated with increased GSH:GSSG ratio and reduced thiol concentrations, which, in addition to reduced circulating LDL, probably decreased oxLDL concentrations within the cohort. In addition, a marked reduction in total cholesterol concentrations in hyperbilirubinemic Gunn rats is presented (Gunn 0.57±0.09 versus control 1.69±0.40 mmol/L; P<0.001), arguing for a novel role for bilirubin in modulating lipid status in vivo. These findings implicate the physiological importance of bilirubin in protecting from atherosclerosis by reducing thiol and subsequent lipoprotein oxidation, in addition to reducing circulating LDL concentrations.
Keyword Cardiovascular disease
Bile pigment
Free radicals
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Human Movement and Nutrition Sciences Publications
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