Exploring the potential application of glucuronides as a prognostic biomarker for disease.

Abstract

The detoxification pathway in the liver is the vital pathway for detoxifying xenobiotics and endogenous molecules in all vertebrates. The majority of molecules require three phases for detoxification, phase I preparation, phase II conjugation and phase III excretion. Research to date demonstrates how human gene polymorphisms and lifestyle factors may alter the fate of the molecule. Additionally, research to date indicates that genotyping can be useful for personalised medicine before administering a drug, the information is used to inform the patient which drug can be or cannot be used for treatment. This is to prevent adverse toxicological reactions during treatment of a disease. Therefore, monitoring the fate of glucuronides in relation to diseases, should have invaluable potential in detection of relevant diseases at earlier stages. The glucuronide species may reflect disease causation influences by genetics and non-genetic factors. For instance, in disease influenced by lifestyle factors, the glucuronides may include glucuronides that have been produced from xenobiotic molecules that have been through glucuronidation. Since research have not addressed the relation of the fate of glucuronide species and diseases. It is important to clarify the concept for disease prognostics based on glucuronide species in their excretion. Therefore, the aim of the research is to explore the potential application of glucuronides for disease prognosis and disease, by revealing the relationship between glucuronides and disease. The research presented in the thesis demonstrate that glucuronide species are potentially associated with diseases. For instance, to date, in prostate cancer three glucuronides are associated with the disease: androsterone glucuronide (ADT-g), androstane-3α, 17β-diol glucuronide (3α-diol-G), and androstane-3a, 17b-diol-17 glucuronide (3α-diol-17G), when prostate cancer is influenced by gene variants. In type 2 diabetes, influenced by lifestyle, three glucuronides are associated with the disease: 2-phenylethanol glucuronide, deoxycholic acid 3- glucuronide, and androstanediol glucuronide.