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

There are no files associated with this record.

Title Reduced circulating oxidized LDL is associated with hypocholesterolemia and enhanced thiol status in Gilbert syndrome
Author Boon, Connie; Hawkins, Clare L.; Bisht, Kavita; Coombes, Jeff S.; Bakrania, Bhavisha; Wagner, Karl-Heinz; Bulmer, Andrew Cameron
Journal Name Free Radical Biology and Medicine
Year Published 2012
Place of publication Australia
Publisher Elsevier
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
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1016/j.freeradbiomed.2012.03.002
Volume 52
Issue Number 10
Page from 2120
Page to 2127
ISSN 0891-5849
Date Accessioned 2012-07-05
Date Available 2013-06-03T23:26:29Z
Language en_US
Research Centre Griffith Health Institute; Heart Foundation Research Centre
Faculty Griffith Health Faculty
Subject Cardiology (incl Cardiovascular Diseases)
URI http://hdl.handle.net/10072/47257
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

Show simple item record

Griffith University copyright notice