Dionne Arthur (PhD Student)
University of Queensland

Project Title
A new approach for the assessment of biological effects induced by oxidative stress

Biography
Dionne completed her Bachelor of Science at the Victoria University of Wellington, New Zealand majoring in biochemistry and molecular biology. She completed her Honours at the same university in cell and molecular bioscience. Dionne is currently enrolled as a PhD student at the University of Queensland in which her project is part of a larger one funded by CRC CARE.

Start Date
January 2007

Project Details
Biomarkers reflect changes in biological systems that are related to exposure, or effects of toxins. The most intuitive need for a biomarker is to help diagnose disease. The ideal biomarker would be one that detects stress at an early stage before damage/disease occurs.

Bilirubin oxidative metabolites (BOMs) have been reported to be elevated in urine and plasma of rats and humans under stress. Exposure to environmental contaminants has been implicated in the development of stress. This project aims to establish a relationship between the concentrations of BOMs found in urine and plasma with the exposure of environmental contaminants. This will be performed in a mouse model with the idea that these BOMs can be used as biomarkers to assess the early response to stress in mammals. Monitoring toxicity of these contaminants will provide a realistic approach towards risk assessment with regards to the health of animals, both aquatic and land-dwelling. The project outcomes will also provide information that will establish a platform for the development of a commercial diagnostic kit to detect urinary and plasma BOMs.

PhD Thesis Abstract - Summary
Arsenic exposure causes chronic disease and cancer in various organs in humans. The liver is a target organ for arsenic toxicity. The most accepted mechanism of arsenic toxicity involves oxidative stress. The initial response to oxidative stress is defensive, and involves numerous antioxidant defence systems. Two enzyme systems that have been reported to play an important role in cellular defence during metal-induced oxidative stress include haem oxygenase-1 (HO-1) and cytochrome P450 2a5 (Cyp2a5). It was found that both enzymes are involved in bilirubin (BR) homeostasis, where Cyp2a5-dependant BR oxidation is elevated when BR levels increase due to HO-1 induction. The oxidative metabolism of BR is an important pathway of detoxification in addition to glucuronidation, however the oxidative products were not identified.

The observations made during the PhD study suggest that (i) both murine Cyp2a5 and human CYP2A6 enzymes oxidise BR to form BOMs; (ii) concurrent induction of HO-1 and Cyp2a5 during arsenic-mediated oxidative stress may protect the liver against lipid peroxidation; and (iii) production of BOMs may be mediated by Cyp2a5 BR oxidation and subsequently eliminated in the urine.