The physiological relevance of bile pigments In vitro to in vivo evidence of antioxidant, anti- mutagenic and anti-carcinogenic potential and their mechanisms of action

Funding Body: FWF-Austrian Science Fund, Project No. P21162

Duration: 2009-2012

Principal Investigator:

Karl-Heinz Wagner
Andrew Bulmer, Co-Project leader, Griffith University, Australia

Main Project group:

Christine Mölzer, PhD student
Marlies Wallner, PhD student

AMES Test group (first project part):  

Christine Mölzer, PhD student
Hedwig Huber, Master student
Gesa Viktoria Ziesel, Master student
Andrea Steyrer, Master student

Human Trial

Marlies Wallner, PhD student
Nadja Antl, Master student
Barbara Rittmannsberger, Master student
Katharina Marisch, Master student
Melanie Gierer, Master student
Alexandra Kauril, Master student
Marie-Theres Pappenheim, Master student

Cooperation partners:

Dr. Andrew Bulmer, School of Medical Science, Griffith University, Australia
Dr. Joanne Therese Blanchfield, School of Molecular and Microbial Sciences, The University of Queensland, Australia.  
Prof. Jirka Neuzil, School of Medical Science, Griffith University, Australia.
Prof. Verena Dirsch, Department of Pharmacognosy, Molecular Targets, University of Vienna.
Prof. Henrik Poulsen, Department of Clinical Pharmacology, University Hospital, Copenhagen, Denmark.

Short description: Bile pigments are naturally occurring compounds that are produced in the human body. These pigments, called bilirubin and biliverdin, are intensely coloured and can been seen in the skin during jaundice (bilirubin) and in the green (biliverdin) and yellow (bilirubin) colour of bruises. In the past, bile pigments and bilirubin in particular have been thought of as useless or even harmful compounds because jaundice is associated with disease and occasionally can be toxic. However, in the past 20 years, a growing number of research groups have investigated the possible beneficial effects of bile pigments in the human body. Very important early findings showed bile pigments were part of a group of compounds called antioxidants, thereby protecting from free radicals that are produced constantly in the human body. Following studies showed that people with mildly elevated bilirubin concentrations in their blood, suffered lower rates of heart disease, which causes sudden death from heart attack. More recent evidence suggests that bile pigments also prevent compounds that cause cancer, from damaging the genetic program of cells called DNA. Co-incidentally, people with elevated bilirubin concentrations are also less likely to suffer from cancer. Before the real importance of bile pigments in the human body can be realised, the mechanism (the ‘how’) of their protection from heart disease and cancer must be established. When the bile pigments’ mechanism of action is known then scientists can investigate new ways of altering the amount of circulating bile pigments, which existing research suggests could prevent the largest killers of people in Western society (cardio-vascular disease and cancer). A series of studies within this project will focus on revealing the protective effects of bile pigments on the development of cancer. Importantly, the studies will investigate how bile pigments protect from cancer, which is currently unknown. The studies progress from pure science investigations (chemistry) to more complex biological experiments in bacteria, animal and human cells, humans and finally in animals. These studies will progressively establish the mechanism and potential of bile pigments to protect from cancer, finally testing whether the compounds could be beneficial in humans and animals. Once the effects of bile pigments in animal models of cancer have been established, we will be in a better position to comment on the physiological importance of these poorly understood naturally occurring compounds and apply our knowledge in humans.

ISI Publications prior to the project:

Bulmer AC, Ried K, Wagner K-H (2008): Antimutagenic effects of bile pigments. Mut Res Rev, 658:28-41 [Toxicology: IF=7.579; Rank: 3/73 (Top 20%)] view article

Bulmer AC, Ried K, Coombes JS, Blanchfield JT, Toth I, Wagner K-H (2007): The antimutagenic and antioxidant effects of bile pigments in the Ames Salmonella test. Mut. Res. Genetic Toxicology and Environment Mutagenesis, 629:122-132 view article

Non ISI Publications:

Short description of the project on the FWF homepage view article

Article about the project in the online journal from the University of Vienna ("Gelb, aber gesund - anti-oxidative Gallenfarbstoffe") view article