Low Density Lipoprotein Peroxidation Research Articles

Comparative Susceptibility to Oxidation of Different Classes of Blood Plasma Lipoproteins.

The kinetics of free radical peroxidation of different classes of blood plasma lipoproteins (nanoparticles involved in lipid transport in the body) was studied. The susceptibility of atherogenic low-density lipoproteins (LDLs) to the Cu2+-initiated free radical peroxidation in vitro was found to be more than ten times higher than that of antiatherogenic high density lipoproteins (HDLs). The baseline content of acyl hydroperoxy derivatives of phospholipids (primary products of free radical peroxidation) in the outer layer of LDL particles in vivo measured per particle exceeded the baseline content of these compounds in HDL particles by more than an order of magnitude. The susceptibility to oxidation of the HDL2 subfraction of HDLs was higher than the susceptibility of total HDL fraction and HDL3 subfraction. The data obtained confirm an important role of free radical peroxidation of LDLs in the molecular mechanisms of vascular wall damage in atherosclerosis.

Protective Effect of Lusianthridin on Hemin-Induced Low-Density Lipoprotein Oxidation.

Oxidation of low-density lipoprotein (LDL) plays a crucial role in the pathogenesis of atherosclerosis. Hemin (iron (III)-protoporphyrin IX) is a degradation product of hemoglobin that can be found in thalassemia patients. Hemin is a strong oxidant that can cause LDL oxidation and contributes to atherosclerosis in thalassemia patients. Lusianthridin from Dendrobium venustrum is a phenolic compound that possesses antioxidant activity. Hence, lusianthridin could be a promising compound to be used against hemin-induced oxidative stress. The major goal of this study is to evaluate the protective effect of lusianthridin on hemin-induced low-density lipoprotein oxidation (he-oxLDL). Here, various concentrations of lusianthridin (0.25, 0.5, 1, and 2 µM) were preincubated with LDL for 30 min, then 5 µM of hemin was added to initiate the oxidation, and oxidative parameters were measured at various times of incubation (0, 1, 3, 6, 12, 24 h). Lipid peroxidation of LDL was measured by thiobarbituric reactive substance (TBARs) assay and relative electrophoretic mobility (REM). The lipid composition of LDL was analyzed by using reverse-phase HPLC. Foam cell formation with he-oxLDL in RAW 264.7 macrophage cells was detected by Oil Red O staining. The results indicated that lusianthridin could inhibit TBARs formation, decrease REM, decrease oxidized lipid products, as well as preserve the level of cholesteryl arachidonate and cholesteryl linoleate. Moreover, He-oxLDL incubated with lusianthridin for 24 h can reduce the foam cell formation in RAW 264.7 macrophage cells. Taken together, lusianthridin could be a potential agent to be used to prevent atherosclerosis in thalassemia patients.

Possible mechanism of antioxidant action of dinitrosyl iron complexes

The antioxidant effect of dinitrosyl iron complexes (DNICs) was studied in various model systems. DNICs with glutathione ligands effectively inhibited Cu2+-induced peroxidation of low density lipoproteins (LDL). The antioxidant effect of DNICs with phosphate ligands and free reduced glutathione (GSH) was less pronounced. In addition, DNICs with glutathione suppressed the formation of reactive oxygen species during co-oxidation of lecithin liposomes and glucose. Free radical oxidation in this system was induced with a lipophilic azo initiator and evaluated by luminol-dependent chemiluminescence. NO sharply stimulated chemiluminescence during co-oxidation of glucose and liposomes, thus suggesting the formation of potent oxidants under these conditions. Glutathione DNICs scavenge the superoxide radical anion generated in the xanthine-xanthine oxidase system. Superoxide production was assessed by lucigenin-dependent chemiluminescence and electron paramagnetic resonance (EPR) spectroscopy. Chemiluminescence revealed the dose-dependent character of antiradical effect of glutathione DNICs; moreover, these complexes turned out to be more efficient than GSH. EPR spectra of the adducts of the DEPMPO spin trap with free radicals suggest that the interaction of glutathione DNICs and superoxide does not result in the formation of the thiyl radical of glutathione. Here we propose a mechanism of the antioxidant action of glutathione DNICs, suggesting that unstable intermediate complexes are formed upon their interaction with superoxide or lipid radicals. Further, as a result of intramolecular rearrangement, these intermediates decompose without the free radical as the by-products.

Serum paraoxonase-1 levels as an indicator of oxidative stress in patients with vitiligo

ObjectiveTo evaluate the use of serum paraoxonase-1 (PON1) activity as an indicator of oxidative stress in patients with active generalized vitiligo.BackgroundVitiligo is an acquired cutaneous disorder of pigmentation, characterized by destruction of melanocytes. One of the major hypotheses in the pathogenesis of vitiligo is the oxidative stress hypothesis. In patients with vitiligo, lower levels of PON1 prevent lipoprotein peroxidation and oxidation of low-density lipoprotein and cholesterol.Patients and methodsA case–control study was conducted on 40 patients: 20 patients with recent active generalized vitiligo and 20 age-matched and sex-matched healthy volunteers served as controls. All the included patients underwent full history taking, full examination, routine laboratory investigations, and assessment of serum PON1.ResultsThe serum PON1 level in patient group A (101.64 ± 25.48) was significantly lower than that in the control group B (181.88 ± 95.12) (P < 0.001). There was a significant negative correlation between serum PON1 level and vitiligo area severity index score (r = −0.780, P < 0.001).ConclusionVitiligo is probably mediated through a process of oxidative stress and imbalance of oxidant–antioxidant system. Oxidative stress present in vitiligo disease can be determined by measurement of serum PON1 in these patients.

Wide Biological Role of Hydroxytyrosol: Possible Therapeutic and Preventive Properties in Cardiovascular Diseases.

The growing incidence of cardiovascular disease (CVD) has promoted investigations of natural molecules that could prevent and treat CVD. Among these, hydroxytyrosol, a polyphenolic compound of olive oil, is well known for its antioxidant, anti-inflammatory, and anti-atherogenic effects. Its strong antioxidant properties are due to the scavenging of radicals and the stimulation of synthesis and activity of antioxidant enzymes (SOD, CAT, HO-1, NOS, COX-2, GSH), which also limit the lipid peroxidation of low-density lipoprotein (LDL) cholesterol, a hallmark of atherosclerosis. Lowered inflammation and oxidative stress and an improved lipid profile were also demonstrated in healthy subjects as well as in metabolic syndrome patients after hydroxytyrosol (HT) supplementation. These results might open a new therapeutic scenario through personalized supplementation of HT in CVDs. This review is the first attempt to collect together scientific literature on HT in both in vitro and in vivo models, as well as in human clinical studies, describing its potential biological effects for cardiovascular health.

The effect of passive and active exposure to tobacco smoke on lipid profile parameters and the activity of certain membrane enzymes in the blood of women in the first trimester of pregnancy

The effect of tobacco smoke on lipid peroxidation, the lipid profile and membrane-bound enzymatic activity in the first trimester of pregnancy was investigated.In the plasma of women with active exposure to tobacco smoke, we have found increased lipid peroxidation and higher total concentrations of cholesterol, triglycerides and low-density lipoproteins in the blood, as well as a decreased concentration of high-density lipoproteins. A higher concentration of low-density lipoproteins and a lower concentration of high-density lipoproteins were also found in the plasma of passive smokers. In contrast, women who smoked before pregnancy had only a higher low-density lipoprotein concentration. In the group of active and passive smoking women, lower arylesterase and phosphotriesterase activities of paraoxonase were observed, while the lactonase activity of paraoxonase decreased only in the group of active smoking women. In women with active exposure to tobacco smoke, a higher activity level of alanine aminopeptidase and γ-glutamyltransferase in the plasma was found.It is important to monitor the lipid profile during pregnancy, especially when exposure to tobacco smoke occurs.

Antioxidative and Inhibitory Effects of the Fruiting Body of Black Lingzhi Mushroom, Amauroderma rugosum (Agaricomycetes), on LDL Oxidation and HMG-CoA Reductase Activity.

Amauroderma rugosum fruiting bodies possess excellent cardiovascular benefits, including antioxidative, antihyperlipidemic, antihypertensive, antiinflammatory, anti-platelet aggregation, and antithrombotic effects. In this article, we describe our investigations of the in vitro antioxidant activity and in vitro antiatherosclerotic potential through inhibitory effects on low-density lipoprotein (LDL), LDL peroxidation, and 3-hydroxy3-methylglutaryl-coenzyme A (HMG-CoA) reductase catalytic activity using various fruiting body extracts partitioned with an organic solvent. Among 5 extracts/fractions tested, the semipolar ethyl acetate (EA) fraction demonstrated good antioxidant capacity based on total phenolic content, 2,2-diphenyl-1-picrylhydrazyl free radical scavenging, ferrous ion-chelating ability, cupric ion-reducing antioxidant capacity, and lipid peroxidation assays. The EA fraction also showed the strongest inhibitory effect on Cu2+-induced LDL oxidation via thiobarbituric acid reactive substances formation and HMG-CoA reductase activity. Chemical analysis conjointly identified 10 phenolic compounds (4 benzoic acid derivatives, 3 flavonoids, 1 cinnamic acid, 1 hexahydroxydiphenic acid dilactone, and 1 xanthone derivative), some of which play pivotal roles in arresting the physiopathogenesis of atherosclerosis, thereby attenuating the risk of cardiovascular events occurring.

Assessment of the relationship between serum paraoxonase activity and epicardial adipose tissue in hemodialysis patients.

Paraoxonase-1 (PON-1) is a high-density lipoprotein-associated (HDL) enzyme, which has been shown to reduce susceptibility to low-density lipoprotein (LDL) peroxidation. Epicardial adipose tissue (EAT) is a marker of atherosclerosis. The aim of this study was to determine the relationship between PON-1 activity and EAT in hemodialysis (HD) patients. This is a cross-sectional study conducted on 72 (43 males) HD patients with end-stage renal disease. Serum levels for lipid profiles, C-reactive protein, calcium, phosphate, and parathyroid hormone were measured. PON-1 activity was also measured and compared to the rate of enzymatic hydrolysis of paraoxon to p-nitrophenol. Echocardiography was used to measure EAT thickness (EATT). The correlation between PON-1 and EATT was assessed, while independent predictors of EATT in HD patients were similarly assessed using multivariate regression analysis. There was a significant low mean value of PON-1 activity in HD patients compared with the control group (82.1±31.6 vs. 164.3±61.5 U/l, p=0.0001) and significant high mean value of EATT in HD patients, compared with controls (6.2±1.7 vs. 3.9±1.1mm, p=0.0001). In addition, there was a significant negative correlation between PON-1 activity and EATT (r=-0.484, p=0.0001) and a significant positive correlation between PON-1 activity and HDL-C (r=0.417, p=0.0003). PON-1, total cholesterol, triglycerides, LDL, HDL, age, and body mass index were found to be independent predictors of EATT. Our study demonstrated that PON-1 activity was significantly lower in HD patients compared with healthy controls and that PON-1 activity was inversely correlated with EATT in this population.

Phenolics of selected lentil cultivars: Antioxidant activities and inhibition of low-density lipoprotein and DNA damage

Free, esterified, and insoluble-bound phenolics were extracted from selected lentil cultivars. Total phenolics, flavonoids and proanthocyanidin contents were determined. Catechin, epicatechin and procyanidins B were predominant in all fractions of all tested samples as evaluated using HPLC-DAD-ESI-MSn. Methyl vanillate, procyanidin dimer A, and prodelphinidin dimer A were identified and quantified in lentils for the first time. Procyanidin dimer A was detected only in the insoluble-bound form, methyl vanillate was present in the esterified and insoluble-bound one and prodelphinidin dimer A was found in all forms. The presence of unrevealed compounds present only in the insoluble-bound form shows that ignoring the presence of phenolics linked to the cell wall of lentils may underestimate their potential health benefits. The antioxidant activities and the inhibition of cupric ion-induced human low-density lipoprotein peroxidation and peroxyl radical induced supercoiled plasmid DNA strand scission demonstrated that lentil seeds may be considered as a functional food.

Evaluation of the Antioxidant Activities of Ya-hom Intajak, a Thai Herbal Formulation, and its Component Plants

Purpose: To evaluate the antioxidant effect of 80 % ethanol extract and its n-hexane and dichloromethane fractions of Ya-hom Intajak, and its 47 medicinal plants components.Methods: The 80 % ethanol extract and its n-hexane and dichloromethane fractions were investigated on human low-density lipoprotein (LDL) peroxidation by thiobarbituric acid reactive substances (TBARS) assay. Antioxidant effect was also determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity and ferric reducing antioxidant power (FRAP) assays.Results: The extract of Ya-hom Intajak exhibited moderate DPPH scavenging activity with an IC50 value of 99.08 µg/ml and a FRAP value of 1.12 mmol FeSO4/g. Among the individual plants, Terminalia chebula Retz., Caesalpinia sappan L., Cinnamomum bejolghota (Buch.-Ham.) and Ci. verum J. Presl, showed strong antioxidant activities. T. chebula was the most potent plant in the DPPH assay while Ca. sappan had the highest FRAP value. Among the extracts, the dichloromethane fraction showed the highest inhibitory effect on LDL peroxidation with a half maximal inhibitory concentration (IC50) value comparable to that of probucol (0.82 µg/ml). Pearson correlation analysis revealed that total phenolic content (TPC) showed high positive correlations with FRAP (r = 0.908, p &lt; 0.01) and DPPH activities (r= 0.648, p &lt; 0.01).Conclusion: Ya-hom Intajak is a valuable source of natural antioxidants and has a potential application as a cardiovascular protective formulation.Keywords: Ya-hom Intajak, Antioxidant activity, Terminalia chebula Retz., Caesalpinia sappan L., Cinnamomum bejolghota (Buch.-Ham.), Ci. verum J. Presl , Phenolic content

The initiation of free radical peroxidation of low-density lipoproteins by glucose and its metabolite methylglyoxal: a common molecular mechanism of vascular wall injure in atherosclerosis and diabetes.

It was found that glucose in the range of concentrations 12.5-100mM stimulated Cu(2+)-mediated free radical peroxidation of low-density lipoproteins (LDL) from human blood plasma. Considering the kinetic parameters of LDL peroxidation we proposed that intensification of this process may be caused by formation of free radical intermediates of glucose auto-oxidation. Addition of SOD to the medium inhibited LDL oxidation, indicating the formation of superoxide anion-radicals under autoxidation of glucose. Similarly, SOD inhibited free radical peroxidation of liposomes from egg lecithin in the presence of glucose that confirms the generation of superoxide radicals under co-oxidation of unsaturated lipids and glucose. Normalization of glucose level in the blood of patients with type 2 diabetes mellitus during therapy was accompanied by a significant decrease in LDL oxidation in vivo (the decrease in primary and secondary lipoperoxidation products). The formation of superoxide anion-radicals was observed during interaction of aminoacid L-lysine with a product of glucose oxidative metabolism-methylglyoxal, but not with a product of lipoperoxidation malonyldialdehyde. In accordance with the foregoing the administration of sugar-lowering drug metformin, which binds and utilizes methylglyoxal, caused a stronger inhibition of LDL peroxidation in the blood of patients with diabetes mellitus, probably due to decrease in methylglyoxal-dependent generation of superoxide anion-radicals. Based on the results we set out the hypothesis about autocatalytic mechanism of free radical reactions involving natural dicarbonyls and suppose the common molecular mechanism of vascular wall injury in atherosclerosis and diabetes.

Effect of Persea americana (avocado) fruit extract on the level of expression of adiponectin and PPAR-γ in rats subjected to experimental hyperlipidemia and obesity.

Persea americana, commonly known as avocado, is traditionally consumed fruit which possesses body fat lowering capacity. Adiponectin plays an important role in regulating obesity. In this study, the effect of hydro-alcoholic fruit extract of P. americana (HAEPA) on the level of blood lipids, glutathione, lipid peroxidation products, adiponectin and peroxisome proliferator activated receptor (PPAR)-γ expressions was investigated in rats fed a high-fat diet (HFD). Male Sprague Dawley rats were divided into four groups: groups 1 and 2 were fed normal rat chow (5% fat) and groups 3 and 4 were fed HFD (23% fat) for a period of 14 weeks. In addition, groups 2 and 4 rats were administered orally with 100 mg/kg body weight of HAEPA from third week. After 14 weeks, rats were sacrificed, and serum/plasma levels of total cholesterol, phospholipids, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and adiponectin were determined. The mRNA expression of adiponectin, PPAR-γ and protein expression of PPAR-γ were also evaluated. The body mass index (BMI), total fat pad mass and adiposity index were significantly decreased in HAEPA co-administered rats than in HFD-fed rats. The levels of LDL and lipid peroxides were significantly higher in HFD group than in HFD+HAEPA group. Levels of reduced glutathione, adiponectin, mRNA expression of adiponectin, PPAR-γ and protein expression of PPAR-γ were found to be increased in HFD+HAEPA group than in HFD group. The hypolipidemic effect of HAEPA is also evidenced by the histological observations in liver, heart and adipose tissue. The results indicate that HAEPA exhibits hypolipidemic activity probably by increasing the mRNA expression of adiponectin and PPAR-γ, which reduce the risk of hyperlipidemia and obesity.

Is atherosclerosis an autoimmune disease?

Immunologic research into pathogenic mechanisms operating in autoimmune-mediated atherosclerosis initially focused on adaptive immunity. Current interest is directed to more basic inflammatory mechanisms. Chronic inflammation (innate immunity-associated) may trigger initial events that can lead to atherosclerotic cardiovascular disease. This chronic inflammation may start early in life and be perpetuated by classic atherosclerosis risk factors. Lipid peroxidation of low-density lipoprotein seems to be a key event in the initiation and progression of atherosclerosis. Oxidized low-density lipoprotein triggers inflammatory and immunogenic events that promote endothelial dysfunction and the synthesis and secretion of pro-inflammatory cytokines, leading to an autoimmune response capable of accelerating the intracellular accumulation of lipids within atherosclerotic plaques. Oxidized low-density lipoprotein binds β2-glycoprotein I to form circulating complexes found in both autoimmune and non-autoimmune atherosclerosis. It is likely that β2-glycoprotein I and/or these complexes contribute to early atherogenesis by stimulating pro-inflammatory innate immunity through endogenous sensors and inflammasome/interleukin-1 pathways. We discuss the chronic inflammatory (innate) and autoimmune (adaptive) responses operating in atherosclerosis to discern the role of autoimmunity in atherosclerotic cardiovascular disease.

Low-Density Lipoprotein (LDL)-Antioxidant Biflavonoids from Garcinia madruno

Six biflavonoids were isolated from G. madruno, one of which, 7''-O-(6''''-acetyl)-glucoside of morelloflavone, is a new compound identified on the basis of 1D, 2D NMR (HMQC and HMBC) spectroscopic methods and chemical evidence. The antioxidant activity of the biflavonoids against low-density lipoprotein (LDL) peroxidation induced with Cu2+, was studied by means of a TBARS assay. The antioxidant potential of a biflavonoid fraction (BF) was also evaluated and correlated with its biflavonoid content. The flavanone-(3→8'')-flavone biflavonoids displayed antioxidant activity, particularly morelloflavone, which was significantly more potent than quercetin, with a CE50 of 12.36 μg/mL. Lipid peroxidation, was also significantly reduced in the presence of the BF (EC50 = 11.85 μg/mL). These results suggest that the BF is an excellent antioxidant.

Human Hp1-1 and Hp2-2 Phenotype-Specific Haptoglobin Therapeutics Are Both Effective In Vitro and in Guinea Pigs to Attenuate Hemoglobin Toxicity

Infusion of purified haptoglobin (Hp) functions as an effective hemoglobin (Hb) scavenging therapeutic in animal models of hemolysis to prevent cardiovascular and renal injury. Epidemiologic studies demonstrate the phenotype heterogeneity of human Hp proteins and suggest differing vascular protective potential imparted by the dimeric Hp1-1 and the polymeric Hp2-2. In vitro experiments and in vivo studies in guinea pigs were performed to evaluate phenotype-specific differences in Hp therapeutics. We found no differences between the two phenotypes in Hb binding and intravascular compartmentalization of Hb in vivo. Both Hp1-1 and Hp2-2 attenuate Hb-induced blood pressure response and renal iron deposition. These findings were consistent with equal prevention of Hb endothelial translocation. The modulation of oxidative Hb reactions by the two Hp phenotypes was not found to be different. Both phenotypes stabilize the ferryl (Fe(4+)) Hb transition state, provide heme retention within the complex, and prevent Hb-driven low-density lipoprotein (LDL) peroxidation. Hb-mediated peroxidation of LDL resulted in endothelial toxicity, which was equally blocked by the addition of Hp1-1 and Hp2-2. The present data do not provide support for the concept that phenotype-specific Hp therapeutics offer differential efficacy in mitigating acute Hb toxicity.

Hibiscus sabdariffa leaf polyphenolic extract inhibits LDL oxidation and foam cell formation involving up-regulation of LXRα/ABCA1 pathway

The oxidative modification of low-density lipoprotein (LDL) is involved in the pathogenesis of atherosclerotic lesions through the formation of macrophage-derived foam cells. In the present study, we aimed to investigate the anti-atherosclerotic effect of Hibiscus sabdariffa leaf polyphenolic extract (HLP), which is rich in flavonoid. The inhibitory effect of HLP on oxidation and lipid peroxidation of LDL was defined in vitro. HLP showed potential in reducing foam cell formation and intracellular lipid accumulation in oxidised-LDL (ox-LDL)-induced macrophage J774A.1 cells under non-cytotoxic concentrations. Molecular data showed these influences of HLP might be mediated via liver-X receptor α (LXRα)/ATP-binding cassette transporter A1 (ABCA1) pathway, as demonstrated by the transfection of LXRα siRNA. Our data implied that HLP up-regulated the LXRα/ABCA1 pathway, which in turn led to stimulation of cholesterol removal from macrophages and delay atherosclerosis. These results suggested that HLP potentially could be developed as an anti-atherosclerotic agent.

Characterization of a novel high-density lipoprotein antioxidant capacity assay and its application to high-density lipoprotein fractions

ObjectivesHigh-density lipoprotein (HDL) inhibits low-density lipoprotein (LDL) oxidation therefore it is involved in the prevention of atherogenesis. HDL particles originating from different persons possess different antioxidant activities. Our aim was to establish a method for the measurement of HDL antioxidant capacity, which is suitable for testing the antioxidant activity of HDL samples in a wide range and produces data relevant to in vivo HDL–LDL interactions. Hemin was used as pro-oxidant since its role in the course of LDL oxidation and atherosclerosis is proven. MethodsHemin-induced and hydrogen peroxide catalyzed lipid peroxidation of LDL was performed in the presence and absence of HDL. The time interval required for reaching the maximum reaction velocity (ΔTVmax) was determined and HDL antioxidant capacity was expressed as the ratio of the ΔTVmax with and without HDL. HDL fractions (n=8) isolated by ultracentrifugation from healthy donors were analyzed and their antioxidant capacities were compared. ResultsIn parallel with their increasing density, HDL fractions expressed increasing antioxidant capacity (106.12–194.12%). Within-run and within-laboratory CVs of the method were 1.72–1.87% and 4.09–4.93%, respectively. Alterations of hydrogen peroxide concentration in the range of 50–125μmol/L did not influence the assay results, while the elevation of hemin concentration (between 3 and 9μmol/L) resulted in decreased antioxidant capacity. The values for hemin degradation correlated well with conjugated diene formation. ConclusionsHemin-induced LDL oxidation is a reliable assay system to test the antioxidant capacity of HDL and its subpopulations.

The Antioxidant and Free Radical Scavenging Activities of Chlorophylls and Pheophytins

Chlorophylls are important antioxidants found in foods. We explored the mechanisms through which the a and b forms of chlorophyll and of pheophytin (the Mg-chelated form of chlorophyll) reduce oxidation: we used comet assay to measure prevention of H2O2 DNA damage; we tested for quenching of 1,1-diphenyl-2-picrylhydrazyl (DPPH); we measured the ability to chelate Fe(II); and, we tested their ability to prevent formation of thiobarbituric acid reactive substances (TBARS) during Cu-mediated peroxidation of low density lipoprotein (LDL) in a chemical assay. All chlorophylls and pheophytins showed significant dose-dependent activity in the assays, with the pheophytins being the strongest antioxidants. Thus, these chemicals can prevent oxidative DNA damage and lipid peroxidation both by reducing reactive oxygen species, such as DPPH, and by chelation of metal ions, such as Fe(II), which can form reactive oxygen species.

Oxidized-LDL and Paraoxonase-1 As Biomarkers of Coronary Artery Disease in Patients with Sleep-Disordered Breathing

Coronary Artery Disease (CAD) and Sleep Disordered Breathing (SDB) are both oxidative stress disorders. SDB intermittent hypoxia induces oxidative stress, and reduces NO(·) availability, causing endothelial dysfunction. Low-density lipoprotein (LDL) peroxidation is involved in atherosclerosis, and is reported in SDB. Oxidized LDL (ox-LDL) and malondialdehyde (MDA) are lipid peroxidation markers. High-density lipoprotein (HDL) presents antiatherosclerotic properties related to paraxonase-1 (PON-1) activity. PON-1 hydrolyseyses lipid peroxides as ox-LDL. This study compares the relationship of HDL and PON-1, the lipid peroxidation markers ox-LDL and MDA, and 8-OHdG DNA damage marker in the association of SDB and CAD. 29 controls and 27 cases with CAD (defined as > 30% coronary narrowing) patients were included. The apnea-hypopnea index (AHI), and several lipid and oxidative stress parameters were measured in these patients. AHI is increased in CAD patients, and PON-1 activity and HDL levels are decreased. Regression analyseyses showed that lower PON-1 activity and higher ox-LDL levels are important CAD predictors, compared to HDL or MDA levels and present an age-dependent increase. Nitrites and nitrates, indirect NO(·) markers, are positive vs correlated with PON-1 and are negatively correlated to ox-LDL. SDB is not correlated to PON-1 activity decrease or ox-LDL increase. AHI is inversely correlated to HDL levels. These results indicate that PON-1 and ox-LDL are important predictors of CAD, however they may not be directly related to SDB.

The influence of glucose on the free radical peroxidation of low density lipoproteins in vitro and in vivo

It was shown that glucose in concentration 12.5-100 mM stimulated of Cu(2+)-mediated free radical peroxidation of low density lipoproteins (LDL) from human blood plasma. On the base investigation of kinetic parameters of LDL peroxidation it was stated that intensification of this process in the conditions of our experiments is caused by formation of free radical intermediates of glucose autoxidation during active oxygen species generation in the presence of metal ions with variable valence. It was found that glucose level normalization in the blood of patients with type 2 diabetes during therapy accompanied by significant decreasing of LDL oxidizing. During therapy with sugar-lowering drug metformin which utilizate methylglyoxal the LDL peroxidation from blood diabetes mellitus in vivo inhibited in more higher degree probably in consequence of decreasing of methylglyoxal-dependent generation of superoxide anion radicals as was shown by us early [Biochemistry (Moscow), 2007, 72: 1081-1090; Biochemistry (Moscow), 20(09, 74: 461-466].