ScienceAsia 31 (2005): 369-381 |doi: 10.2306/scienceasia1513-1874.2005.31.369

Kinetic Modeling of Lipoprotein Peroxidation Initiated by Copper and Azo Compounds

Somchai Yanarojana,^a Udom Chantharaksri,^a Prapin Wilairat^b and Yongwimon Lenbury^c*

 
ABSTRACT: Oxidation of low density lipoprotein (LDL) has been postulated as the main cause of atherogenesis, resulting in formation of foam cells, triggering of various pathways, and leading to the development of the disease. Therefore, antioxidants would naturally be expected to attenuate the progress of atherosclerosis. - Tocopherol (-TocH) is the most abundant form of vitamin E in nature and the major antioxidant of biological membranes. -TocH is also present at a much higher concentration than other antioxidants in plasma lipoproteins. The large amount of -TocH present in LDL leads to the expectation that lipid peroxidation would be strongly inhibited by -TocH. However, advanced atherosclerotic plaques are not deficient in the presence of antioxidants such as vitamins C and E, despite the occurrence of massive lipid oxidation. Thus conventional mechanism associated with the antioxidant properties of -TocH cannot explain why lipid peroxidation occurs in atherosclerotic lesions in the presence of compounds that are usually considered to be antioxidants. A kinetic model was developed and applied to explore the mechanism of lipid peroxidation process under various conditions and to examine the possible occurrence of lipid peroxidation in the presence of -tocopherol. The model incorporated many factors, that were not included in previous models but we believe to play important roles in the different outcome of the process. As a result, the numerical simulation illustrated that lipid peroxidation in the lipoprotein particle could occur in the presence of vitamins E (-TocH) and C under certain conditions, including high initiation rate, high initial -TocH level, low ratio of [vitamin C]/[-TocH], and small lipoprotein particles. The kinetic scheme developed in this study defined the type of relationship that -TocH in an environment exhibits either pro- or antioxidative property. Thus, antioxidant and pro-oxidant effects of tocopherol merely depend on the condition in which its properties are exhibited.

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a Department of Pharmacology, Mahidol University, Bangkok 10400, Thailand.
b Department of Chemistry, Mahidol University, Bangkok 10400, Thailand.
c Department of Mathematics, Mahidol University, Bangkok 10400, Thailand.

* Corresponding author, E-mail: scylb@mahidol.ac.th

Received 2 Mar 2005, Accepted 21 Jun 2005