Medizinische Universität Graz - Research portal
Selected Publication:
Wagner, B.
Development of an Analytical Platform for the Detection of Oxidative Stress in the Human Organisms
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Graz Medical University; 2015. pp.
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- Authors Med Uni Graz:
- Advisor:
- Fauler Günter
- Scharnagl Hubert
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- Abstract:
- Free radical-induced lipid peroxidation has been implicated in several human diseases, such as cardiovascular diseases, cancer, neurodegenerative diseases and diabetes. The physiological levels of reactive oxygen species (ROS) and other free radicals are regulated by an antioxidant defence system. However, when the rate of radical production exceeds the elimination capacity of the antioxidant defence system, cell damage occurs due to the formation of artificially transformed nucleic acids, proteins, and lipids. Isoprostanes are a unique class of prostaglandin-F2-like compounds formed in vivo and in vitro by free radical attack on arachidonic acid as well as on other polyunsaturated long-chain fatty acids (PUFAs). Several F2-isoprostanes have the potential to be used as specific markers for the extent of damage of biological membranes caused by reactive oxygen species. In particular, 8-iso-Prostaglandin F2a has been established as a reliable marker of oxidative stress due to its direct correlation with lipid peroxidation as well as its low abundance under normal physiological conditions in plasma and urine. The field of redox biology serves as a basis for non-invasive markers to assess physiological regulation processes and reactive oxygen species production in vivo. An analytical platform for the simultaneous profiling of oxidative stress markers (8-iso-Prostaglandin F2a and 8-hydroxy-2’-deoxyguanosine) and bioactive lipid mediators from polyunsaturated fatty acids in human body fluids has been developed. Using solid phase extraction and ultra-high performance liquid chromatography coupled to tandem mass spectrometry a easy to handle and less time consuming method could be accomplished. This approach represents a sensitive and versatile analytical technique for qualitative and quantitative analysis targeted markers, which can be constituted as a useful tool for the determination of oxidative stress biomarkers. The main goal of this thesis is to establish of a high-throughput assay for ROS markers and oxylipins that could become important as a screening tool in nutritional and clinical research. Overall, this thesis discribes a powerful analytical tool to examine ROS markers and oxylipin profiles as it provides a generic and comprehensive lipidomics approach for simultaneous identification and quantitation of lipid mediators.