Competitive and seasonal oxidative stress in elite alpine ski racers.

We investigated competitive- and long-term oxidative stress during a competition season in eight top-ranked members of the Austrian Men's Alpine Ski Team. Serum total peroxides, antibody titers against oxidized LDL (oLAb) and lag time of the degradation of the fluorophore 1-palmitoyl-2-((2-(4-(6-phenyl-trans-1,3,5-hexatrienyl)phenyl)ethyl)-carbonyl)-sn-glycero-3-phosphocholine were measured, along with plasma concentrations of ascorbate, alpha- and gamma-tocopherol, beta-carotene, uric acid and the lipid status. Competitive stress was indicated through an increased post-race uric acid level (286 +/- 50 microM pre-race vs 456 +/- 77 microM post-race, P<0.001) in December. Long-term effects were already apparent in November, with the highest concentrations of total peroxides (680 +/- 458 microM H(2)O(2) equivalents vs December 47 +/- 58 microM H(2)O(2) equivalents and January 15 +/- 28 microM H(2)O(2) equivalents, P<0.001) and a concomitant decrease in oLAb titers with an antibody trough in December (439 +/- 150 mU/mL vs baseline 1036 +/- 328 mU/mL; P=0.003). In January, after recovery, they attained nearly pre-season levels of oxidative stress biomarkers. This study indicates midseason oxidative stress in top-level skiers, which was associated with the performance in these athletes.

The Genome Austria Tissue Bank (GATiB).

In the context of the Austrian Genome Program, a tissue bank is being established (Genome Austria Tissue Bank, GATiB) which is based on a collection of diseased and corresponding normal tissues representing a great variety of diseases at their natural frequency of occurrence from a non-selected Central European population of more than 700,000 patients. Major emphasis is put on annotation of archival tissue with comprehensive clinical data, including follow-up data. A specific IT infrastructure supports sample annotation, tracking of sample usage as well as sample and data storage. Innovative data protection tools were developed which prevent sample donor re-identification, particularly if detailed medical and genetic data are combined. For quality control of old archival tissues, new techniques were established to check RNA quality and antigen stability. Since 2003, GATiB has changed from a population-based tissue bank to a disease-focused biobank comprising major cancers such as colon, breast, liver, as well as metabolic liver diseases and organs affected by the metabolic syndrome. Prospectively collected tissues are associated with blood samples and detailed data on the sample donor's disease, lifestyle and environmental exposure, following standard operating procedures. Major emphasis is also placed on ethical, legal and social issues (ELSI) related to biobanks. A specific research project and an international advisory board ensure the proper embedding of GATiB in society and facilitate international networking.

A sensitive chemiluminescence method to measure the lipoxygenase catalyzed oxygenation of complex substrates.

Oxidative modification of low-density lipoprotein (LDL) has been implicated as a patho-physiological process in early atherogenesis and 15-lipoxygenases (15-LOX) may be involved. While studying the in vitro kinetics of the 15-LOX/LDL interaction, we found that the conventional spectrophotometric assays failed in the range of substrate saturation owing to the high optical density of concentrated LDL solutions. Therefore, we developed a much more sensitive assay system which was based on peroxide induced isoluminol enhanced chemiluminescence. With this method reliable kinetic data were obtained at LDL concentrations of up to 1 mg/ml. To validate this luminometric method the kinetic parameters of 15-LOX catalyzed oxygenation of linoleic acid (Km=3.7 microM, kcat=17 s-1) were determined and we observed a good agreement with previously published data obtained with a spectrophotometric assay. Moreover, we found that the kinetic constants of 15-LOX catalyzed LDL oxidation (Km=0.64 microM, kcat=0.15 s-1) are quite different from those of free fatty acid oxygenation and that the cholesterol esters are preferentially oxidized during 15-LOX/LDL interaction. Vitamin E depletion does not reduce the rate of LDL oxidation and analysis of the structure of the oxygenation products suggests that the majority of the products were formed via direct LOX catalyzed oxidation of LDL ester lipids. The luminometric method described here is not restricted to the measurement of LOX catalyzed LDL oxidation, but may also be used to determine kinetic constants for the oxidation of other complex substrates such as biomembranes or liposomes.

Ascorbate prevents prooxidant effects of urate in oxidation of human low density lipoprotein.

Uric acid and ascorbic acid are important low molecular weight antioxidants in plasma. Their interactions and combined effect on Cu(2+)-catalysed oxidation of human low density lipoprotein were studied in vitro. It was found that uric acid alone becomes strongly prooxidant whenever it is added to low density lipoprotein shortly after the start of oxidation (conditional prooxidant). Ascorbic acid, which is present in human plasma at much lower concentrations (20-60 microM) than urate (300-400 microM), is in itself not a conditional prooxidant. Moreover, ascorbate prevents prooxidant effects of urate, when added to oxidising low density lipoprotein simultaneously with urate, even at a 60-fold molar excess of urate over ascorbate. Ascorbate appears to have the same anti-prooxidant effect with other aqueous reductants, which, besides their antioxidant properties, were reported to be conditionally prooxidant. Such interactions between ascorbate and urate may be important in preventing oxidative modification of lipoproteins in the circulation and in other biological fluids.

Ceruloplasmin as low-density lipoprotein oxidase: activation by ascorbate and dehydroascorbate.

The ability of ceruloplasmin (Cp) to oxidize low-density lipoproteins (LDL) in the presence of water-soluble antioxidants was investigated and a reaction mechanism proposed. Ascorbate strongly enhanced LDL oxidation, but only after its rapid consumption. Dehydroascorbate enhanced Cp-mediated LDL oxidation even more strongly. Lipid-soluble antioxidants and water-soluble peroxides did not show noticeable activation. However, loading of LDL with lipid hydroperoxides increased the initial oxidation rate. We conclude that Cp mediates a localized redox cycle, where reduction of Cp-Cu2+ is effected by water-soluble reductants and reoxidation by liposoluble hydroperoxides.

Antioxidant role of melatonin in lipid peroxidation of human LDL.

The antioxidant effect of melatonin on LDL oxidation was studied in vitro using either a thermolabile initiator or copper ions to induce lipid peroxidation. Loading of LDL with melatonin showed only weak protection against oxidative damage as compared to alpha-tocopherol. In the presence of high concentrations of melatonin (1000 mol/mol LDL) in the medium a clear protective effect was found during lag- and propagation phase, albeit weaker than after loading with alpha-tocopherol. It is concluded that melatonin is not incorporated into LDL in sufficient concentrations to prevent lipid peroxidation effectively. When melatonin is present in the incubation medium during oxidation, a partitioning equilibrium between aqueous and lipid phase is established. Only under these conditions can melatonin act as a chain breaking antioxidant. The concentrations required, however, are far beyond those found in human plasma. Therefore, the data in this study do not support a direct physiological relevance of melatonin as an antioxidant in lipid peroxidation processes.

Copper can promote oxidation of LDL by markedly different mechanisms.

Oxidation of LDL (0.1 microM) in PBS with copper concentrations ranging from 0.03 to 10 microM, equal to 0.3-100 Cu2+/LDL, was investigated by monitoring the formation of conjugated dienes at 234 nm. With all 8 LDL samples examined, the kinetics changed strongly at submicromolar Cu2+ concentrations. Based on time-course of the formation of conjugated dienes, cholesteryl linoleate hydroxides and hydroperoxides as well as the antioxidant consumption, two oxidation types were distinguished. Type A oxidations, observed at relatively high Cu2+ concentrations of 10-100 Cu2+/ LDL, represented the conventional kinetics of LDL oxidation with an inhibition period (= lag-time) followed by a propagation phase. In contrast, type C oxidations proceeded after a negligibly short lag time followed by a distinct propagation phase. The rate of this propagation increased rapidly to 0.5 mol diene/mol LDL and then slowed down in the presence of alpha-,gamma-tocopherols and carotenoids, which were consumed faster than tocopherols. The increase in diene absorption was due to the formation of both hydroxides and hydroperoxides suggesting a high initial decomposition of hydroperoxides. At submicromolar concentrations of about 0.1 to 0.5 microM, type C and type A oxidation can be combined resulting in 4 consecutive oxidation phases, i.e. 1st inhibition and 1st propagation (belonging to type C), followed by 2nd inhibition and 2nd propagation (belonging to type A). Increasing copper concentrations lowered the 1st propagation and shortened the 2nd inhibition periods until they melted into one apparent kinetic phase. Decreasing [Cu2+] increased the 1st propagation and 2nd inhibition but lowered the 2nd propagation phase until it completely disappeared. A threshold copper concentration, denoted as Cu(lim), can be calculated as a kinetic constant based on the Cu2+-dependence for the rate of 2nd propagation. Below Cu(lim), LDL oxidation proceeds only via type C kinetics. The Cu2+-dependence of the oxidation kinetics suggests that LDL contains two different Cu2+ biding sites. Cu2+ at the low-affinity binding sites, with half-saturation at 5-50 Cu2+/LDL, initiates and accelerates the 2nd propagation by decomposing lipid hydroperoxides. Cu2+ bound to the high-affinity binding sites, with half-saturation at 0.3-2.0 Cu2+/LDL, is responsible for the 1st propagation. Arguments in favor and against this propagation being due to tocopherol mediated peroxidation (TMP) are discussed. If the lag-time concept is extended to the conjugated diene curves seen for combined oxidation profiles, then a true inhibition phase does not apply to this time interval, but instead represents the time elapsed before the onset of the 2nd propagation phase.

Hypochlorite induces the formation of LDL(-), a potentially atherogenic low density lipoprotein subspecies.

Oxidation of low density lipoprotein (LDL) induced by hypochlorous acid (HOCl) leading to LDL(-), a minimally oxidized subspecies of LDL, was investigated. LDL(-) is characterized by its greater electronegativity and oxidative status, and is found in plasma in vivo. Its concentration was found to be elevated under conditions that predispose humans to atherosclerosis. We found that HOCl also converts LDL rapidly to an even more oxidized state, identified as LDL(2-), which is more electronegative than LDL(-). After milder oxidation for short durations, formation of LDL(-) takes place while less LDL(2-) is formed. Under these conditions, addition of methionine not only suppressed further oxidation of LDL but also favored the formation of LDL(-) over LDL(2-), possibly by removing chloramines at lysyl residues of LDL. The presence of lipoprotein-deficient plasma did not prevent HOCl-mediated conversion of LDL to more electronegative species. It is concluded that the HOCl-mediated conversion of LDL into more electronegative species might be physiologically relevant.

N-acetylserotonin is a better extra- and intracellular antioxidant than melatonin.

Both melatonin and its precursor N-acetylserotonin have been reported to exert antioxidant properties both in vitro and in vivo. Since little is known about their antioxidant activity in lymphocytes, we investigated their effects on spontaneous and on oxidant-induced reactive oxygen species formation in human peripheral blood lymphocytes in comparison to the antioxidant trolox, a water-soluble analogue of alpha-tocopherol. Both melatonin and N-acetylserotonin exhibited antioxidant properties against t-butylated hydroperoxide- and diamide-induced reactive oxygen species formation in peripheral blood lymphocytes. N-acetylserotonin turned out to be about three times more effective than melatonin. In resting cells, the intracellular reactive oxygen species concentration was only decreased by N-acetylserotonin and trolox, melatonin had no effect. In t-butylated hydroperoxide-mediated cell death, N-acetylserotonin was as effective as trolox in protecting peripheral blood lymphocytes from cell death and required 10-fold lower concentrations than melatonin. Furthermore, in an aqueous cell-free solution, the capacity of N-acetylserotonin to scavenge peroxyl radicals was much higher than that of melatonin. These results clearly indicate N-acetylserotonin to be a much better antioxidant than melatonin.

Prooxidant activity of melatonin promotes fas-induced cell death in human leukemic Jurkat cells.

The antioxidant activity of melatonin (MEL) has been considered to constitute part of its physiological as well as pharmacological effects. However, as described herein we found a profound prooxidant activity of micro- to millimolar concentrations of MEL in the human leukemic Jurkat cell line. This prooxidant effect was increased in glutathione-depleted cells and counteracted by antioxidants. As a consequence MEL promoted fas-induced cell death. These data therefore indicate that MEL may be a modulator of the cellular redox status, but does not necessarily act as an intracellular antioxidant.

Mechanistic aspects of the relationship between low-level chemiluminescence and lipid peroxides in oxidation of low-density lipoprotein.

In this study oxidation of low-density lipoprotein (LDL) induced by different Cu2+ concentrations was investigated. Lipid peroxidation was assessed by monitoring low-level chemiluminescence (LL-CL), conjugated diene hydroperoxide (CD) and alpha-tocopherol (TocOH), the major lipophilic antioxidant in LDL. At high Cu2+ concentration, LDL oxidation was characterised by CD formation, LL-CL emission and TocOH consumption. At low Cu2+ concentration, CD formation was independent of LL-CL and occurred in the presence of TocOH. Thus, two different mechanisms lead to lipid peroxide formation in LDL. The combination of CD assay and LL-CL monitoring makes it possible to distinguish the autocatalytic mechanism of CD formation and that associated with TocOH, found at a high and a low rate of initiation, respectively.

Relationship between classic risk factors, plasma antioxidants and indicators of oxidant stress in angina pectoris (AP) in Tehran.

Cardiovascular disease (CVD) in general seems to be the leading cause of death in the Eastern Mediterranean Region (EMR) including Iran. This may be due to classic risk factors such as high triglyceride (TG), high total cholesterol (TC), and low levels of high density lipoprotein cholesterol (HDL-C). The impact of antioxidants as potentially protective risk factors against early coronary heart disease (CHD) is unknown in Iran. Therefore, relationships between angina and plasma antioxidants and indicators of lipid peroxidation were investigated in a case-control study. In this study, 82 cases of previously undiagnosed angina pectoris (AP), identified by a modified WHO Rose chest pain questionnaire and verified by electrocardiography during treadmill exercise testing, were compared with 146 controls selected from the same population of over 4000 male civil servants aged 40-60 years. Subjects with AP declared significantly less physical activity and had higher serum TG [means (S.E.M.) 2.32 (0.18) versus 1.61 (0.07) mmol/l] but lower HDL-C [1.01 (0.04) versus 1.18 (0.03) mmol/l] than age-matched controls. Levels of total serum cholesterol, low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) [Lp(a)] were not significantly different between the two groups, while the ratio of LDL-C/HDL-C was significantly higher [4.51 (0.23) versus 3.54 (0. 11)] for subjects with AP than for the controls. There was no significant difference in plasma levels of alpha-tocopherol, vitamin C, alpha- and beta-carotene. However, retinol [1.90 (0.06) versus 2. 09 (0.05)] and beta-cryptoxanthin [0.398 (0.04) versus 0.467 (0.03)] were significantly lower in AP. Furthermore, angina cases exhibited a higher index of lipid peroxidation than controls (e.g. malondialdehyde, MDA; 0.376 (0.010) versus 0.337 (0.009) micromol/l). On multiple logistic regression analysis, retinol with odds ratio (OR) of 0.644 [95% confidence interval (CI; 0.425-0.978)], beta-cryptoxanthin, with an OR of 0.675 (CI; 0.487-0.940), oxidation indices, MDA with OR of 1.612 (95% CI; 1.119-2.322) and LDL-C/HDL-C ratio with OR of 2.006 (95% CI; 1.416-2.849) showed the most significant independent associations with AP in this group of Iranians. In conclusion, the state of lipid peroxidation as well as the status of special antioxidants may be co-determinants of AP in Iran, in parallel with the influence of classical risk factors for cardiovascular disease.

Monitoring of low density lipoprotein oxidation by low-level chemiluminescence.

A method for monitoring low-density lipoprotein (LDL) oxidation by low-level chemiluminescence (LL-CL) is described in this study. The kinetic indices obtained with this procedure, in particular lag-time and K value (related to prooxidant activity of Cu2+ bound to LDL) are compared with those of the established UV-absorbing conjugated diene assay. The correlation of lag-time values obtained by LL-CL and conjugated diene assay was very high both in the case of Cu2+- and peroxyl-radical-mediated oxidation (r = 0.99). By using the transient free radical scavenging activity of butylated hydroxytoluene, a calibration of LL-CL for lipid peroxyl radical and termination rate was obtained. The spectral analysis of LL-CL from oxidizing LDL shows a maximum peak between 420 and 500 nm, corresponding to the emission of triplet carbonyl compounds. LL-CL allows continuous and direct monitoring of LDL oxidation as extraction and derivatization of lipid peroxidation products are not required. Moreover, some limitations of UV spectroscopy such as by absorbing compounds need not be considered. Therefore, the present procedure represents a simple and convenient tool for continuous monitoring of LDL oxidation which may be applied to mechanistic and clinical studies.

Prooxidant and antioxidant properties of Trolox C, analogue of vitamin E, in oxidation of low-density lipoprotein.

Trolox C (Trolox), a water-soluble analogue of vitamin E lacking the phytyl chain, was investigated with respect to its effect on the oxidation of low-density lipoprotein (LDL). Trolox was added at different time points of LDL oxidation induced by Cu2+ and aqueous peroxyl radicals. In the case of Cu2+ -induced LDL oxidation, the effect of Trolox changed from antioxidant to prooxidant when added at later time points during oxidation; this transition occurred whenever alpha-tocopherol was just consumed in oxidizing LDL. Thus, in the case of Cu2+ -dependent LDL oxidation, the presence of lipophilic antioxidants in the LDL particle is likely to be a prerequisite for the antioxidant activity of Trolox. When oxidation was induced by peroxyl radicals, as a model of metal-independent oxidation, the effect of Trolox was always antioxidant, suggesting the importance of Cu2+ /Cu+ redox-cycling in the prooxidant mechanism of Trolox. Our data suggest that, in the absence of significant amounts of lipophilic antioxidants, LDL becomes highly susceptible to oxidation induced by transition metals in the presence of aqueous reductants.

Methods for monitoring oxidative stress, lipid peroxidation and oxidation resistance of lipoproteins.

After a brief discussion of lipid peroxidation mechanism and the action of antioxidants and their potential to exhibit prooxidant effects, we give an overview on the clinical relevance of oxidative stress parameters. Many diseases are associated with oxidative stress e.g. by radical damage, among them atherosclerosis, diabetes mellitus, chronic renal failure, rheumatoid arthritis, and neurodegenerative diseases, and in many cases the investigation of parameters of oxidative stress has brought substantial insights into their pathogenesis. We then briefly review methods for the continuous monitoring of lipid peroxidation processes in vitro, which has helped in elucidating their mechanism and in some more detail cover such methods which have been proposed more recently to assess oxidative status and antioxidant activity in biological samples.

Site-specific effect of radical scavengers on the resistance of low density lipoprotein to copper-mediated oxidative stress: influence of alpha-tocopherol and temperature.

The radical scavenging capacity of active nitroxide spin label radicals located at different depths in the surface monolayer of native and alpha-tocopherol enriched low density lipoprotein (LDL) has been evaluated at early stages of copper-mediated lipid peroxidation. Spin labels induced a concentration-dependent prolongation in lag time and a pronounced decrease in the initial rate of conjugated diene (CD) formation. These effects strongly argue for a protective, antioxidative action of spin labels, which in turn become destroyed with the extent of oxidation by radical recombination reactions. The results revealed that the decrease in spectral intensity proceeds at a higher rate for nitroxide radicals located in a more hydrophobic environment. The loss in spin label activity is accompanied by simultaneous alpha-tocopherol consumption and progresses rather independently of initial alpha-tocopherol content. The data provided no evidence that spin labels either save alpha-tocopherol or compete with it for radicals. The authors, therefore, deduce that due to enhanced accessibility and mobility, spin labels located in the interior of LDL eliminate lipid-derived radicals, which otherwise would promote lipid peroxidation. Lowering of temperature clearly below the core-lipid phase transition temperature of LDL exerts a significant effect on the kinetics of copper-induced LDL oxidation, whereas the characteristics of the radical scavenging mechanisms of the spin label molecules located in the surrounding phospholipid monolayer are conserved. Taken together, the susceptibility of LDL to primary oxidative stress conditions was efficiently retarded by small amounts of radical scavengers. This effect was more pronounced for nitroxide radicals embedded deeper in the phospholipid monolayer and was rather independent of alpha-tocopherol enrichment.

The effect of glycosaminoglycans and proteoglycans on lipid peroxidation.

Recent investigations show that glycosaminoglycans (GAGs) and proteoglycans (PGs) have the ability to affect lipid peroxidation, one the best characterized forms of free radical mediated biological damage. A protective effect of these extracellular matrix (ECM) components has been demonstrated in various experimental systems, including fatty acids and liposomes, where oxidation was induced by transition metals, including copper and iron. The effect was specific and dependent on the type and structural features of GAGs and PGs. The mechanism of peroxidation inhibition was likely to be dependent, at least to a large extent, on the sequestration of transition metals by GAG chains. Thus, it is conceivable that GAGs in the ECM and in the pericellular space may contribute to protecting cells against free radical damage. It is of particular interest that in certain tissues (cornea and aorta) aging was associated with a decrease of content of the GAGs which were most effective as anti-oxidant. This suggests that age-induced modifications of ECM composition in certain tissues may increase the susceptibility to oxidative stress. The investigation on the effect of GAGs on lipoprotein oxidation led to apparently conflicting results. An interesting reconciliation is possible, according to which GAGs exerted their protective effect under experimental conditions not compatible with the formation of lipoprotein-GAG complexes; rather, lipoproteins exhibited increased susceptibility to metal-catalyzed oxidation (MCO), possibly due to structural modifications of the particle after binding to GAGs or PGs. This process is likely to occur in the intimal matrix of arteries.

Effects of dietary fatty acids on the composition and oxidizability of low-density lipoprotein.

OBJECTIVE: The objective of this study was to compare the effects of dietary monounsaturated fatty acids (MUFA), n-6 and n-3 polyunsaturated fatty acids (PUFA) on LDL composition and oxidizability. DESIGN, SETTING AND SUBJECTS: Sixty-nine healthy young volunteers, students at a nearby college, were included. Six subjects withdrew because of intercurrent illness and five withdrew because they were unable to comply with the dietary regimen. INTERVENTIONS: The participants received a 2-week wash-in diet rich in saturated fatty acids (SFA) followed by diets rich in refined olive oil, rapeseed oil or sunflower oil for 4 weeks. Intakes of vitamin E and other antioxidants did not differ significantly between the diets. RESULTS: At the end of the study, LDL oxidizability was lowest in the olive oil group (lag time: 72.6 min), intermediate in the rapeseed oil group (68.2 min) and highest in the sunflower oil group (60.4 min, P<0.05 for comparison of all three groups). Despite wide variations in SFA intake, the SFA content of LDL was not statistically different between the four diets (25.8-28.5% of LDL fatty acids). By contrast, the PUFA (43.5%-60.5% of LDL fatty acids) and MUFA content of LDL (13.7-29.1% of LDL fatty acids) showed a wider variability dependent on diet. CONCLUSIONS: Enrichment of LDL with MUFA reduces LDL susceptibility to oxidation. As seen on the rapeseed oil diet this effect is independent of a displacement of higher unsaturated fatty acids from LDL. Evidence from this diet also suggests that highly unsaturated n-3 fatty acids in moderate amounts do not increase LDL oxidizability when provided in the context of a diet rich in MUFA.

Effects of elderberry juice on fasting and postprandial serum lipids and low-density lipoprotein oxidation in healthy volunteers: a randomized, double-blind, placebo-controlled study.

BACKGROUND: In a recent pilot study, the intake of elderberry juice resulted in a significant decrease in serum cholesterol concentrations and an increase in low-density lipoprotein (LDL) stability. This study was designed to verify the preliminary results. OBJECTIVE: We investigated the impact of elderberry juice on cholesterol and triglyceride concentrations as well as antioxidant status in a cohort of young volunteers. DESIGN: Study A: The randomized, placebo-controlled trial for studying the effect of anthocyanes on lipid and antioxidant status, 34 subjects took capsules with 400 mg spray-dried powder containing 10% anthocyanes t.i.d. equivalent to 5 ml elderberry juice for 2 weeks. A subgroup of 14 subjects continued for an additional week to test for resistance to oxidation of LDL. Study B: To investigate the short-term effects on serum lipid concentrations, six subjects took a single dose of 50 ml of elderberry juice (equivalent to 10 capsules) along with a high-fat breakfast. RESULTS: In the placebo-controlled study, there was only a small, statistically not significant change in cholesterol concentrations in the elderberry group (from 199 to 190 mg/dl) compared to the placebo group (from 192 to 196 mg/dl). The resistance to copper-induced oxidation of LDL did not change within 3 weeks. In the single-dose experiment increases in postprandial triglyceride concentrations were not significantly different when the six subjects were investigated with and without elderberry juice. CONCLUSIONS: Elderberry spray-dried extract at a low dose exerts a minor effect on serum lipids and antioxidative capacity. Higher, but nutritionally relevant doses might significantly reduce postprandial serum lipids.

Simulation of lipid peroxidation in low-density lipoprotein by a basic "skeleton" of reactions.

A minimal kinetic model describing lipid peroxidation in low-density lipoprotein (LDL) has been set up. Models have been calculated by numeric integration of the differential equations describing this system consisting of seven reactions and eleven reactants in a single compartment. The model describes the usually observed behavior of the reaction system, showing that the crucial intermediate is the lipid peroxyl radical (LOO.). During different stages of the reaction, depending on the presence of antioxidants (alpha-tocopherol), different pathways in the reaction scheme become active. Simulation also demonstrates that tocopherol-mediated propagation can occur under certain conditions, i.e., a low rate of initiation. This, however, does not mean that tocopherol enhances lipid peroxidation in LDL, as without tocopherol the process would be much faster. Further extension of the basic model by inclusion of a hypothetical antioxidant leads to a model which is capable of describing Cu(2+)-induced LPO over the whole lag phase up to full propagation.