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Title: Role and mechanism of action of the anthocyanin, delphinidin, in protecting endothelial cells against oxidative stress
Author: Goszcz, Katarzyna
ISNI:       0000 0004 5368 1014
Awarding Body: University of Aberdeen
Current Institution: University of the Highlands and Islands
Date of Award: 2016
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Diet-derived polyphenols are believed to have health benefits on account of their antioxidant properties. Cardiovascular health is considered to be a suitable target for antioxidant therapy because oxidative stress is implicit in atherogenesis – the disease process that underpins heart attacks, ischaemic strokes and peripheral vascular disease. Numerous in vitro, in vivo and clinical studies indicate that polyphenols are protective in cardiovascular disease, but their mechanism of action still remains ambiguous. This thesis describes a wide range of studies to characterise the activity and stability of a key polyphenol, delphinidin, found in widely consumed berries, and ultimately to test the hypothesis that delphinidin, at physiologically relevant concentrations (~1 µM), protects cultured human umbilical vein endothelial cells (HUVECs) against oxidative damage via a mechanism that is independent of direct antioxidant activity. Delphinidin aglycone was found to be unstable in tissue culture medium, in which it decomposed rapidly to simple phenolic compounds, including gallic acid. Electron paramagnetic resonance spectroscopy indicated that, if anything, both delphinidin and gallic acid were pro-oxidant rather than antioxidant. Moreover, high concentrations of both delphinidin and gallic acid induced rapid morphological changes in HUVECs, most notably in the formation of vacuoles or vesicles. Treatment of HUVECs with a range of concentrations (1 nM - 100 µM) of delphinidin and gallic acid showed that high (100 µM) concentrations of both were cytotoxic. However, both agents were found to have a protective effect in cells exposed to oxidative stress when present at concentrations of ~1 µM – too low to be due to direct antioxidant activity. Deeper examination of cells treated with delphinidin and gallic acid indicated that the protective effect was perhaps partially mediated by changes in expression of the intracellular antioxidant, glutathione. Taken together, the results in this thesis suggest that metabolic products of delphinidin might be responsible for the antioxidant effects seen on account of initiating cellular defence responses.
Supervisor: Megson, Ian Sponsor: INTERREG IV B North Sea Region Programme
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Anthocyanins ; Endothelial cells ; Oxidative stress