LDL peroxidation

Bedard et al. [7] studied quantitatively the initiation of the peroxidation of human low-density lipoproteins (LDL) with H00702 . In accord with the above findings the initiation rate increased when pH decreased from 7.6 to 6.5. It was suggested that initiation occurred via hydrogen atom abstraction by perhydroxyl radical from endogenous a-tocopherol, which in this process exhibited prooxidant and not antioxidant properties. Neutral, positively, and negatively charged alkyl peroxyl free radicals were the more efficient initiators of LDL peroxidation compared to superoxide. 

It is currently believed that the oxidative modification of low density lipoprotein (LDL) is an important initial event in pathogenesis of atherosclerosis [50], LDL peroxidation initiated by... 

L9. Lee, C., Antioxidant ability of caffeine and its metabolites based on the study of oxygen radical absorbing capacity and inhibition of LDL peroxidation. Clin. Chim. Acta 295, 141-154 (2000). 

As appears from the above, for prevention of atherogenic oxidative modification of LDL in the blood of patients with atherosclerosis HMG-CoA-reductase inhibitors must be used in combination with antioxidants. The most attractive conclusion is that synthetic antioxidant probucol may act in the LDL as a trap for lipid free radicals and may be effective in the prevention of LDL peroxidation in atherogenesis and during cholesterollowering therapy. 

This new strategy consists of the synthesis of molecules that possess hydroxyl groups in such positions that a radical species can be stabilized by mesomery. This feature is found in natural flavonol such as kaemferol that possesses undeniable antioxidant properties. The first published example is a lipophilic analogue of vitamin C, Fig (13) [40]. In this paper, we have proved that the synthesised substituted 2-hydroxyfuran-2-one is a true ascorbic acid analogue. A radical anion that gives very similar data has been generated under the same conditions as for ascorbic acid with a stability somewhat lower and a redox potential lower than those of ascorbyl radical. Its antioxidant properties are also similar to that of ascorbic acid but it inhibits LDL peroxidation induced by Cu2+ or AAPH more efficiently probably due to a higher lipophilicity. 

Iso verbascoside - Inhibition of in vitro Cu (2+)- induced LDL peroxidation Active ... 

Inhibition of in vitro peroxyl radical-induced LDL peroxidation [47]... 

The susceptibility of LDL toward oxidation can be tested in vitro and ex vivo. When LDL are isolated from human plasma and exposed to free copper ions, the amount or velocity of peroxides formed is measured. It is not until aU of the available vitamin E and other antioxidants have been consumed that LDL peroxidation occurs. In line with that theory, many studies have reported that higher intakes of PUFA (linolenate and n-3 LC-PUFA) increase LDL susceptibility to ex vivo oxidation (20-26). 

Ascorbate has been shown to provide protection against plasma lipid and low-density lipoprotein (LDL) peroxidation both in vitro (Frei et al., 1989) and in healthy men consuming ascorbate supplements (Jialal et al., 1990). This may contribute to reduced heart disease risk since oxidatively modified LDL has been implicated as a significant causal factor in the atherosclerotic process (Steinberg,... 

Peroxide assays - peroxide measurement Iodine formation - tihation, ferrous oxidation xylenol orange (FOX) in vitro assay for LDL peroxidation, glutathione peroxidase (GPX) specific for fatty acid peroxides. Cyclooxygenase (COX) used to measure trace peroxides in biological fluids... 

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