Funding Body: various
Duration: 2014-2018
Principal Investigator:
Karl-Heinz Wagner
Main Project group:
Dr. Christine Mölzer (human case-control; in vitro)
Dr. Marlies Wallner (human case-control)
Anela Tosevska, MSc (in vitro; mechanisms)
Claudia Lang MSc (in vitro; mechanisms)
Nazlisadat Seyed Khoei MSc (human case-control; mechanisms)
Human case control study:
Christine Mölzer
Marlies Wallner
Nazlisadat Seyed Khoei
Patrick Zöhrer, Master student
Gajane Jengojan, Master student
Petra Hinterleitner, Master student
in vitro, mechnistic approach
Anela Tosevska
Claudia Lang
Veronika Wimmer, Master student
Most important 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. Verena Dirsch; Assoc. Prof. Elke Heiss, Department of Pharmacognosy, Molecular Targets, University of Vienna.
Assoc. Prof. Rodrig Marculescu and Dr. Daniel Doberer; Clinical Division for Medical/Chemical Diagnostics and Clinic for Clinical Pharmacology, Medical University of Vienna
Short description: Bile pigments are naturally occurring compounds formed in the human body. The main pigments, called bilirubin and biliverdin, are intensely colored and can been seen in the skin during jaundice (bilirubin) and in the green (biliverdin) and yellow (bilirubin) color of bruises. In the past, bile pigments and bilirubin in particular have been thought of useless or even harmful compounds since jaundice is associated with diseases and occasionally can be toxic.
Today their positive effects on the organism are proven, mainly as antioxidants, but in large epidemiological studies it was observed that people with mildly elevated bilirubin concentrations in their blood, suffered lower rates of heart disease and other chronic diseases.
Recently we were able to show that bile pigments (which are all abundant in the human body) were able to reduce the effects of foodborne and chemical mutagens; especially the bile pigment which are found in the human gastrointestinal tract were highly active. In human cancer cell lines bile pigments were able to induce DNA damage and apoptosis. In a human case-control-study, subjects with increased blood bilirubin levels (also known as “Gilbert´s Syndrome”) showed an improved lipid metabolism (with lower risk factors such as total- and LDL-cholesterol or triglycerides), lower mediators for inflammation and a lower body mass index. Interestingly, the effects were more pronounced in older subjects.
Therefore, we focus in this proposal on questions regarding the health promotional effects of hyperbilirubinaemia at molecular and organismic level, adopting a translational approach in order to gain mechanistic answers for observed epidemiological associations between bilirubin and chronic diseases/mortality focusing thereby on CVD and cancer.
These studies will progressively establish the mechanism and potential of bile pigments to protect from cancer and cardiovascular disease, which will offer potential for disease prevention but also in establishing new preclinical biomarker for disease prediction. Specific focus will be given on aging and age related effects.