Physiological Effects of Bilirubin: Protection from Protein Oxidation, Kidney Dysfunction and Regulation of Hepatic Lipid Metabolism

Thumbnail Image
File version
Primary Supervisor

Bulmer, Andrew

Other Supervisors

Toit, Eugene Du

File type(s)

Clinical evidence indicates that hyperbilirubinaemic individuals with Gilbert’s syndrome (GS) are at reduced risk of developing cardiovascular and chronic kidney disease. This thesis consists of five manuscripts which review and explore various mechanisms whereby unconjugated bilirubin (UCB) may prevent cardiovascular disease (CVD) and chronic kidney disease (CKD). The first study of this thesis followed and extended upon the candidate’s Master of Medical Research program. Forty-four age, gender and body mass index matched Gilbert’s syndrome (GS) and healthy controls were recruited and blood was analysed for lipid parameters and plasma antioxidants/oxidative stress status. Individuals with GS had elevated unconjugated bilirubin (UCB), reduced thiol and glutathione concentrations compared to controls. Oxidative stress biomarkers including oxidised glutathione, protein carbonyl and oxidised low-density lipoprotein concentration were significantly reduced in GS and were negatively correlated with UCB concentrations. To better characterise bilirubin’s ability to inhibit atherogenesis based upon its antioxidant capacity, study two investigated the susceptibility of plasma to myeloperoxidase induced oxidation was tested in hyperbilirubinaemic humans and rodents. Plasma with exogenous UCB supplementation (15.6-250 µM) inhibited HOCl (100 µM) and (100 nM)-hydrogen peroxide (H2O2; 50-100 µM) induced chloramine formation in a dose dependent manner. Chloramine formation was significantly reduced in GS plasma and Gunn rat serum and which was negatively correlated with UCB concentrations. Chloramine decomposition, including protein carbonyl and malondialdehyde formations were significantly reduced in a dose-dependent manner. This study suggested that UCB could inhibit protein and lipid oxidation induced by the formation of biologically relevant radicals/oxidants in vitro.

Journal Title
Conference Title
Book Title
Thesis Type

Thesis (PhD Doctorate)

Degree Program

Doctor of Philosophy (PhD)


School of Medical Science

Publisher link
Patent number
Grant identifier(s)
Rights Statement
Rights Statement

The author owns the copyright in this thesis, unless stated otherwise.

Item Access Status



In order to comply with copyright Figures 1.1 and 2.2 have not been published here.

Access the data
Related item(s)

Hyperbilirubinaemic individuals

Gilbert’s syndrome (GS)

Cardiovascular disease (CVD)

Chronic kidney disease (CKD)

Unconjugated bilirubin (UCB)


Kidney dysfunction

Hepatic lipid metabolism

Protein oxidation

Persistent link to this record