Cholesterol ester hydroperoxides

Free fatty acid hydroperoxides and phospholipid hydroperoxides partition into the aqueous methanol layers, whereas triglyceride hydroperoxides and cholesterol ester hydroperoxides are recovered in... 

Abbreviations NL = normolipidemic subjects, HC = hypercholesterolemic, PCOOH = phosphatidylcholine hydroperoxides, CEOOH = cholesterol ester hydroperoxides. LDL subtractions were oxidized with copper at 37°C and monitored at 234 nm continuously, while time points were taken at the propagation half-time (T, ), and the end of the propagation time (T ). 

Ashidate K, Kawamura M, Mimura D, Tohda Fi, Miyazaki S, Teramoto T, Hirata Y, Yamamoto Y (2005) Gentisic acid, an aspirin metabolite, inhibits oxidation of low-density lipoprotein and the formation of cholesterol ester hydroperoxides in human plasma. Fur J Pharmacol 513 173... 

Contrary to LDL, high-density lipoproteins (HDL) prevent atherosclerosis, and therefore, their plasma levels inversely correlate with the risk of developing coronary artery disease. HDL antiatherogenic activity is apparently due to the removal of cholesterol from peripheral tissues and its transport to the liver for excretion. In addition, HDL acts as antioxidants, inhibiting copper- or endothelial cell-induced LDL oxidation [180], It was found that HDL lipids are oxidized easier than LDL lipids by peroxyl radicals [181]. HDL also protects LDL by the reduction of cholesteryl ester hydroperoxides to corresponding hydroperoxides. During this process, HDL specific methionine residues in apolipoproteins AI and All are oxidized [182]. 

The antiatherosclerotic effect of proanthocyanidin-rich grape seed extracts was examined in cholesterol-fed rabbits. The proanthocyanidin-rich extracts [0.1% and 1% in diets (w/w)] did not change the serum lipid profile, but reduced the level of the cholesteryl ester hydroperoxides (ChE-OOH) induced by 2,2/-azo-bis(2-amidinopropane-dihydrochloride (AAPH), the aortic malonaldehyde (MDA) content and severe atherosclerosis. The immuno-histochemical analysis revealed a decrease in the number of the oxidized LDL-positive macrophage-derived foam cells on the atherosclerotic lesions of the aorta in the rabbits fed the proanthocyanidin-rich extract. When the proanthocyanidin-rich extract was administered orally to the rats, proantho-cyanidin was detected in the plasma. In an in vitro experiment using human plasma, the addition of the proanthocyanidin-rich extract to the plasma inhibited the oxidation of cholesteryl linoleate in the LDL, but not in the LDL isolated after the plasma and the extract were incubated in advance. From these results, proanthocyanidins of the major polyphenols in red wine might trap ROSs in the plasma and interstitial fluid of the arterial wall, and consequently display antiatherosclerotic activity by inhibiting the oxidation of the LDL [92]. 

A) Fluorescence/Chemiluminescence Techniques. Lipid hydroperoxides can be reacted with chemiluminescent indicators such as luminol or diphenyl-l-pyrenylphosphine post-HPLC , which allows separation and identification of phospholipid and cholesterol ester peroxides . This technique is applicable to both conjugated and non-conjugated lipids, however it tends to involve a relatively long delay between injection and final fluorescent analysis, and it probably provides inaccurate assessments of total levels of peroxide . ... 

Sevanian et al. (1994) applied GLC and LC/TS/MS for the analysis of plasma cholesterol-7-hydroperoxides and 7-ketocholesterol. Analysis of human and rabbit plasma identified the commonly occurring oxidation products, yet dramatic increases in 7-ketocholesterol and cholesterol-5p, 6P-epoxide were observed. The study failed to reveal the presence of choles-terol-7-hydroperoxides, which were either too unstable for isolation, metabolized or further decomposed. The principal ions of cholesterol oxides monitored by LC/TS/MS were m/z 438 (cholestane triol) m/z 401 (cholesterol-7-hydroperoxide) m/z 401 (7-ketocholesterol) m/z 367 (7a-hydroxycholesterol) m/z 399 (cholesta-3,5-dien-7-one) and m/z 385 (choles-terol-5a,6a-epoxide). The major ions were supported by minor ions consistent with the steroid structure. Kamido et al. (1992a, b) synthesized the cholesteryl 5-oxovaleroyl and 9-oxononanoyl esters as stable secondary oxidation products of cholesteryl arachidonate and linoleate, respectively. These compounds were identified as the 3,5-dinitrophenylhydrazone (DNPH) derivatives by reversed-phase LC/NICI/MS. These standards were used to identify cholesteryl and 7-ketocholesteryl 5-oxovaleroyl and 9-oxononanoyl esters as major components of the cholesteryl ester core aldehydes generated by copper-catalysed peroxidation of low-density lipoprotein (LDL). In addition to 9-oxoalkanoate (major product), minor amounts of the 8, 9, 10, 11 and 12 oxo-alkanoates were also identified among the peroxidation products of cholesteryl linoleate. Peroxidation of cholesteryl arachidonate yielded the 4, 6, 7, 8, 9 and 10 oxo-alkanoates of cholesterol as minor products. The oxysterols resulting from the peroxidation of the steroid ring were mainly 7-keto, 7a-hydroxy and 7P-... 

Table 13.3. Lag time of LDL subfractions during copper initiated oxidation and ratios of phosphatidylcholine (PCOOH) and cholesterol ester (CEOOH) hydroperoxides to polyunsaturated fatty acids ...

Separation of reaction products HPLC or GC analysis of aldehydes, lipid hydroperoxides, cholesterol esters, and phospholipids. 

During a study, there has been evaluated the effect of supplementation with a low dose of co-3, obtained by olive oil, on the oxidative modification of low density lipoprotein (LDL) in a group of healthy volunteers, for 16 weeks. Oxidative modification of LDL was assessed measuring the concentrations of free cholesterol, cholesteryl esters and cholesteryl linoleate hydroperoxide in LDL, following copper-induced lipid peroxidation for 0, 2, 3 and 4 h. LDL eicosapentaenoic acid and docosahexaenoic acid compositions were significantly lower in the group treated with )-3 olive oil than the group treated with w-3 fish oil. 

Other oxidation products include epoxides that can arise from hydroperoxide rearranganent [25-27], but are also formed by enzymic processes [28,29], Products of lipid oxidation may be quantified after formation from simple lipids, for example, oxidation of cholesterol or PUFA. These lipids may be components of more complex lipids like cholesteryl esters [30] or PUFA-containing phospholipids [31]. An analysis of the oxidized products can be performed on the intact lipid or after the individual Upid components are separated by hydrolysis. 

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