Degree Name

PhD (Doctor of Philosophy)

Program

Biomedical Sciences

Date of Award

December 1994

Abstract

The hypothesis that antioxidant vitamins (ascorbate and tocopherols) along with urate protect blood plasma lipids from oxidation was tested. Dietary fat is also an important factor influencing plasma lipid peroxidation. The purpose of this study was to investigate the role of plasma antioxidants and dietary fat on low density lipoprotein (LDL) and plasma lipid oxidation. In the first part of this study, we compared the ability of urate and ascorbate to protect human LDL from in vitro oxidation. LDL oxidation was initiated by 15 mM of a water soluble azo-initiator in the presence or absence of ascorbate or urate. The rate of lipid hydroperoxide (LOOH) formation was increased after the LDL tocopherols were totally consumed, i.e., after the lag phase. Urate (50 $\mu$M) was more effective than ascorbate (50 $\mu$M) in extending the lag phase. Moreover, urate was consumed more slowly than ascorbate under identical oxidation conditions. The combination af 25 $\mu$M ascorbate and 25 $\mu$M urate was more effective in extending the lag phase than ascorbate alone but less effective than urate alone. An empirical mathematical model was developed to describe the oxidation kinetics of LDL tocopherols. In the second part of this study, we studied the role of dietary fat and dietary $\alpha$-tocopherol ($\alpha$-toc) levels on rat plasma oxidation. The fatty acid composition of plasma was found to be modulated by the type of dietary fat. Neither dietary fat nor $\alpha$-toc influenced the plasma levels of water soluble antioxidants (ascorbate, urate and sulfhydryl content). Rat plasma was oxidized either by a water soluble azo-initiator (25 mM) or a lipid soluble azo-initiator (10 mM). In both cases, the rate of LOOH formation in plasma from rats fed butter oil diets was markedly suppressed compared to the plasma from rats fed corn oil diets. When oxidation was initiated by a lipid soluble azo-initiator, plasma from rats fed $\alpha$-toc supplemented diets showed higher LOOH levels than plasma from rats fed $\alpha$-toc deficient diets. Surprisingly, when oxidation was initiated by water soluble azo-initiator, tocopherol appeared to act as a pro-oxidant. The results suggest that urate may be more significant than ascorbate in delaying the consumption of tocopherols in human LDL and that low dietary PUFAs levels are more important in preventing the in vitro oxidation of plasma lipids than high dietary levels of $\alpha$-tocopherol.

Document Type

Dissertation - unrestricted

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