|Title:||Inhibition of oxidant formation by myeloperoxidase|
|Publisher:||University of Sydney.|
Heart Research Institute.
Central Clinical School - RPAH
|Abstract:||Myeloperoxidase (MPO) generates highly reactive hypohalous acids (HOX) which destroy invading pathogens. However, tissue damage and disease result when HOX production becomes uncontrolled; evidence for this has been observed in inflammatory pathologies, including atherosclerosis. Given these observations, effective strategies to minimise this damage are required. A series of compounds, ranging from common drugs, to naturally-occurring compounds and novel compounds, were assessed in this Thesis for their ability to inhibit oxidant production by MPO. Therapeutically-relevant concentrations of paracetamol, and lower concentrations of the structurally-related compound apocynin inhibited HOX production in a dose-dependent manner and resulted in the generation of a dimer. A series of naturally-occurring green tea flavonoids inhibited oxidant production in an additive manner, at levels which may be achieved in vivo. Inhibition of NADPH oxidase by these compounds was also proposed. Novel nitroxide compounds, with enhanced in vivo stability, inhibited MPO at least as equally as their less stable counterparts. The related enzyme, eosinophil peroxidase, was less sensitive to inhibition by these compounds. This Thesis has contributed to the knowledge of MPO inhibitors through the examination of a wide range of existing and novel compounds. Furthermore, additional pathways were suggested to be involved including potential inhibition of NADPH oxidase.|
|Access Level:||Access is restricted to staff and students of the University of Sydney . UniKey credentials are required. Non university access may be obtained by visiting the University of Sydney Library.|
|Rights and Permissions:||The author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.|
|Type of Work:||PhD Doctorate|
|Type of Publication:||Doctor of Philosophy Ph.D.|
|Appears in Collections:||Sydney Digital Theses (University of Sydney Access only)|
|KAJER Tracey - Final thesis.pdf||4.52 MB||Adobe PDF|
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