Susceptibility Of Low-density Lipoprotein Research Articles

Effects of Capsaicin, Dihydrocapsaicin, and Curcumin on Copper-Induced Oxidation of Human Serum Lipids

The oxidation of low-density lipoprotein (LDL) is believed to be the initiating factor for the development and progression of atherosclerosis. The active ingredients of spices such as chili and turmeric (capsaicin and curcumin, respectively) have been shown to reduce the susceptibility of LDL to oxidation. One of the techniques used to study the oxidation of LDL is to isolate LDL and subject it to metal-induced (copper or iron) oxidation. However, whole serum may represent a closer situation to in vivo conditions than using isolated LDL. We investigated the effects of different concentrations (0.1-3 microM) of capsaicin, dihydrocapsaicin, and curcumin on copper-induced oxidation of serum lipoproteins. The lag time (before initiation of oxidation) and rate of oxidation (slope of propagation phase) were calculated. The lag time increased, and the rate of oxidation decreased with increasing concentrations of the tested antioxidants (p < 0.05). A 50% increase in lag time (from control) was observed at concentrations between 0.5 and 0.7 microM for capsaicin, dihydrocapsaicin, and curcumin. This study shows that oxidation of serum lipids is reduced by capsaicinoids and curcumin in a concentration-dependent manner.

A fibre cocktail of fenugreek, guar gum and wheat bran reduces oxidative modification of LDL induced by an atherogenic diet in rats

LDL (low-density lipoprotein) oxidation is a key trigger factor for the development of atherosclerosis. Relatively few studies exist on the impact of dietary fibre on LDL oxidation. This study was undertaken to evaluate the influence of a novel fibre mix of fenugreek seed powder, guar gum and wheat bran (Fibernat) on LDL oxidation induced by an atherogenic diet. Male Wistar albino rats were administered one of the following diets: (1) a control diet that was fibre-free (Group I); (2) an atherogenic diet containing 1.5% cholesterol and 0.1% cholic acid (Group II) or (3) an atherogenic diet supplemented with Fibernat (Group III). Peroxidative changes in low-density lipoprotein (LDL) and the oxidative susceptibility of LDL and the LDL + VLDL (very low-density lipoprotein) fraction were determined. As a corollary to the oxidative modification theory, the titer of autoantibodies to oxidised LDL (oxLDL) was determined at various time points of the study. In addition, plasma homocysteine (tHcy) and lipoprotein (Lp (a)), apolipoprotein (apoB), cholesterol, triglyceride, phospholipid and alpha-tocopherol content of LDL were determined. A decrease in malonaldehyde (MDA) content (p<0.05) and relative electrophoretic mobility (REM) of LDL was observed in the group III rats as compared to the group II rats. An increase in lag time to oxidation (p<0.01) and decrease in maximum oxidation (p<0.01) and oxidation rate (p<0.01) were observed in the LDL + VLDL fraction of group III rats. In group II rats, formation of autoantibodies to oxLDL occurred at an earlier time point and at levels greater than in the group III rats. Fibernat, had a sparing effect on LDL alpha-tocopherol, which was about 51% higher in the group III rats than in the group II rats; apo B content of LDL was reduced by 37.6% in group III rats. LDL of group III rats displayed a decrease in free and ester cholesterol (p<0.01) as compared to that of group II. A decrease in plasma homocysteine (p<0.01) and an increase in GSH (p<0.05) were also observed in group III rats when compared with that of group II. Fibernat administration appears to combat oxidative stress resulting in a trend to lower oxidative modification of LDL. In addition, the cholesterol and apo B content of LDL were reduced significantly with a sparing effect on LDL alpha-tocopherol. This novel fibre preparation could be an effective diet therapy and therefore needs further investigation.

Acarbose ameliorates atherogenecity of low-density lipoprotein in patients with impaired glucose tolerance

Acarbose, an α-glucosidase inhibitor, is administered to control blood glucose levels. The drug also reduces the risk of cardiovascular disease, but the underlying mechanism is still to be elucidated. We therefore hypothesized that treatment with acarbose ameliorates the atherogenecity of low-density lipoprotein (LDL), a key molecule in atherogenesis. Patients with impaired glucose tolerance were or were not treated with acarbose (acarbose-treated group [n = 20] and control group [n = 20], respectively) for 3 months under dietary therapy. The oxidative susceptibility of LDL was determined by measuring lag time for the formation of dienes in the presence of CuSO 4. The lag time was significantly longer in the acarbose-treated group than in the control group before treatment. Moreover, the density gradient lipoprotein separation and disk polyacrylamide gel electrophoresis analyses showed that acarbose reduced the amount of small dense LDL, a more atherogenic and oxidatively susceptible form of LDL. We also found that the fatty acid composition of LDL changed after the treatment: polyunsaturated ( ω-3) fatty acid, a beneficial substance for preventing cardiovascular disease, was significantly increased, whereas saturated fatty acids and triglyceride were decreased in the LDL of the acarbose-treated group. The present findings suggest that acarbose treatment reduces the risk of cardiovascular diseases by ameliorating the atherogenecity of LDL.

Role of ascorbic acid on in vitro oxidation of low-density lipoprotein derived from hypercholesterolemic patients

Background The susceptibility of low-density lipoprotein (LDL) to oxidation is thought to be a crucial factor responsible for atherogenesis. There is substantial evidence for a role of dietary antioxidants in the prevention of atherogenesis and the protective effect of antioxidant nutrients may be mediated through inhibition of the oxidative modification of LDL. Methods We performed in vitro oxidation of LDL derived from normal and hypercholesterolemic individuals in absence and presence of different doses of ascorbic acid. Results: The serum lipid peroxidation level was significantly increased in hypercholesterolemic patients and their LDL has shown a greater propensity towards in vitro oxidation. Hypercholesterolemic LDL required a higher amount of ascorbic acid to reduce its oxidation level as compared to LDL isolated from normocholesterolemic individuals. Conclusion This observation may be of importance in designing future studies of antioxidant supplementation in patients with hypercholesterolemia which is one of the major risk factors for atherosclerosis.

Plasma asymmetric dimethylarginine (ADMA), nitrate and the indices of low-density lipoprotein oxidation

Background Oxidative modification of low-density lipoprotein (LDL) is an important contributor to atherosclerosis. Also, oxidized LDL is suspected to cause accumulation of asymmetric dimethylarginine (ADMA), an endogenous competitive nitric oxide synthase inhibitor, which is suggested to be an independent risk factor for atherosclerosis. This study was performed to evaluate how plasma ADMA is related to plasma nitric oxide production, oxidized LDL and ex vivo susceptibility of LDL to oxidation in mildly hypercholesterolemic otherwise healthy subjects. Methods Plasma ADMA was determined using high performance liquid chromatography tandem mass spectrometry. LDL oxidation was estimated by the lag time and rate of copper-induced LDL oxidation. The nitric oxide production in plasma was estimated based on nitrate (NO 3 −) determination and plasma oxidized LDL was determined by a capture ELISA. Results Low ADMA was a significant determinant for high LDL oxidation rate and concentration of plasma ADMA was associated with nitrate levels. Conclusions There may be an interplay between LDL fatty acid oxidation rate and plasma ADMA and nitrate. We hypothesize that plasma ADMA has a bivalent role: high ADMA may have a protective role in decelerating LDL fatty acid oxidation and also a risk factor for endothelial dysfunction by decreasing availability of nitric oxide.

The Effect of ? -Tocopherol on Copper Binding to Low Density Lipoprotein

The oxidative modification of low density lipoprotein (LDL) may play an important role in atherogenesis. Antioxidants that can prevent LDL oxidation may act as antiatherogens. Our understanding of the mechanism of LDL oxidation and factors that determine its susceptibility to oxidation is still incomplete. Copper is a candidate for oxidizing LDL in atherosclerotic lesions. The binding of copper ions to LDL is usually thought to be a prerequisite for LDL oxidation by copper. Therefore we investigated the effect of ?-tocopherol (as a major fat soluble antioxidant) on copper bound to LDL and furthermore effect of this binding on the susceptibility of LDL to oxidative modification. In this study LDL was isolated from EDTA-plasma (1 mg EDTA/ml blood) by ultracentrifugation using a single-step discontinuous gradient. Then ?-tocopherol was added to LDL and incubated for 1 h at 37° C. The oxidation rate of LDL was estimated by thiobarbitoric acid reactive substances (TBARS) after CuSO4 addition. Finally, the effect of ?-tocopherol on formation of LDL-copper complex by gel filtration was studied. Our results showed that ?-tocopherol (dose dependently) suppressed the formation of TBARS and LDL-copper complex. The ?-tocopherol with concentrations of 10, 50 and 100 µM reduced susceptibility of LDL to oxidative modification approximately by 2, 13 and 21 percent, respectively. Furthermore, addition of ?-tocopherol to the LDL and CuSO4 mixture containing before hand prevented the formation of LDL-copper complex, approximately by 30 percent. In conclusion we found that ?-tocopherol with inhibition of copper binding to LDL may decrease the susceptibility of LDL oxidation to this ion and thus could play a role in prevention of atherosclerosis.

Hemodialysis reduces inhibitory effect of plasma ultrafiltrate on LDL oxidation and subsequent endothelial reactions

Oxidative modification of low-density lipoprotein (LDL) and its deleterious effect on endothelium is implicated in the pathogenesis of atherosclerosis. Endothelium responds to such an insult by upregulating the synthesis of heme oxygenase-1 (HO-1) and ferritin. Endothelial cell damage and dysfunction have been observed in patients with chronic kidney disease (CKD) on maintenance hemodialysis (HD). We studied the effect of low-molecular-weight components of uremic plasma on LDL oxidation and LDL-oxidation-provoked endothelial cell reactions, such as the induction of cytotoxicity and the upregulation of cell-protective HO-1 and ferritin. Plasma ultrafiltrate (molecular weight<5000 Da) from CKD patients on HD or when treated conservatively exhibited a pronounced inhibition on heme-mediated oxidative modification of LDL. Endothelial cell cytotoxicity provoked by LDL oxidation was also attenuated by plasma ultrafiltrate from CKD patients. During HD treatment, a dramatic drop occurred in the retardation of oxidative reactions, and a loss of endothelial cytoprotection exerted by plasma ultrafiltrate was noted. The upregulation of HO-1 and ferritin in response to oxidative stress of LDL was blunted by uremic plasma ultrafiltrate that was released by the end of HD. The decreased antioxidant capacity of ultrafiltrate after HD occurred as a consequence of the intradialytic removal of L-ascorbic acid, uric acid, bilirubin, 3-indoxyl sulfate, indoxyl-beta-D-glucuronide, p-cresol, and phenol. Intradialytic removal of L-ascorbic acid, uric acid, bilirubin, 3-indoxyl sulfate, indoxyl-beta-D-glucuronide, p-cresol, and phenol increases the risk of LDL oxidation and subsequent endothelial cell damage, which underlines the importance of activation of cytoprotective HO-1 and ferritin in endothelium.

We-P14:407 Effect of coffee on the oxidative susceptibility of low-density lipoprotein

We-P14:407 Effect of coffee on the oxidative susceptibility of low-density lipoprotein

Impaired plasma nitric oxide availability and extracellular superoxide dismutase activity in healthy humans with advancing age

This study is aimed to verify the modifications of extracellular superoxide dismutase (EC-SOD) activity and its potential involvement on the mechanism responsible for the impairment of plasma nitric oxide (NO) availability occurring with advancing age in healthy humans. For this purpose, plasma samples were drawn from 40 healthy men, aged 20–92 years, in fasting state and used for measurements of stable end-product nitrite/nitrate (NO x ), as expression of NO availability, EC-SOD activity, thiobarbituric acid reactive substances (TBARS) as marker of lipid peroxidation, Trolox equivalent antioxidant capacity (TEAC) as a measure of plasma total antioxidant capacity, and in vitro susceptibility of low density lipoprotein (LDL) to copper-mediated oxidation, evaluated as lag time. As indicated by our results, advancing age was significantly related to decreased plasma values of NO x ( r = − 0.877, P < 0.001), EC-SOD activity ( r = − 0.888, P < 0.001), TEAC ( r = − 0.647, P < 0.001) and lag time ( r = − 0.621, P < 0.001) as well as to an increased plasma amount of TBARS ( r = 0.858, P < 0.001). NO x plasma level resulted independently predicted by EC-SOD activity and age. EC-SOD activity, in turn, was determined by age and TEAC. Taken together, findings of the present study give further insight into the mechanism related to age-associated endothelial dysfunction, indicating that the decreased EC-SOD activity may be involved in the progressive reduction of plasma NO availability with advancing age through the age-related impairment of oxidant/antioxidant balance.

Alterations in the oxidant‐antioxidant status in prepubertal children with growth hormone deficiency: effect of growth hormone replacement therapy

Growth hormone deficiency (GHD) in adults is associated with increased oxidative stress determined by the underlying GH-IGF-1 axis alterations. Despite GHD being a common diagnosis in children with short stature, no data on the oxidant/antioxidant status are available in this age group. This study was designed to detect differences in oxidative stress parameters between prepubertal GH-deficient children and healthy controls. Furthermore, the effect of 12 months of conventional GH replacement (rGH) on oxidant-antioxidant status was evaluated in the GHD group only. Ten (nine males and one female) prepubertal children (mean age 9.1 +/- 1.3 years) with GHD were recruited and matched for sex and age (9.2 +/- 1.9 years) with 20 healthy controls (18 males and two females). At study entry, lag phase, an index of susceptibility of low density lipoprotein (LDL) to in vitro oxidation, malondialdehyde (MDA) and vitamin E were measured in all subjects. These parameters were also evaluated in GH-deficient children after 12 months of rGH treatment. The lag phase was significantly decreased in GH-deficient children compared to healthy controls (15.50 +/- 7.4 vs. 43.00 +/- 9.2 min; P = 0.0007), while MDA was significantly increased (1.33 +/- 0.38 vs. 0.46 +/- 0.10 nmol/mg; P = 0.0006). Vitamin E levels were significantly decreased (22.44 +/- 9.57 vs. 35.38 +/- 16.49 micromol/l; P = 0.001). IGF-1 and IGFBP-3 correlated directly to lag phase (r = 0.48; P = 0.01; r = 0.63, P = 0.002, respectively) and to vitamin E (r = 0.59, P = 0.003; r = 0.58, P = 0.006, respectively). By contrast, IGF-1 and IGFBP-3 correlated indirectly to MDA (r = -0.47, P = 0.01; r =-0.65, P = 0.002, respectively). After 1 year of rGH therapy, lag phase (39.32 +/- 15.24 min; P = 0.005) and vitamin E (34.9 +/- 7.7 micromol/l; P = 0.005) increased significantly, while MDA decreased significantly (0.71 +/- 0.42 nmol/mg; P = 0.005), reaching normal levels. These data show that children with GHD have substantially increased oxidative stress parameters compared to healthy controls and demonstrate a normalization of these parameters after 1 year of rGH therapy.

L-arginine improves endothelial function and reduces LDL oxidation in patients with stable coronary artery disease

We investigated the effects of oral L-arginine on endothelial function, intravascular oxidative stress, and circulating inflammatory markers in patients with stable coronary artery disease (CAD). Thirty-one stable CAD patients were randomly assigned to oral L-arginine (10 g) or vitamin C (500 mg, an antioxidant, as active control) daily for 4 weeks, with crossover to the alternate therapy after 2 weeks off therapy, in this study. Brachial artery endothelial function studies were performed and serum concentrations of lipids and inflammatory markers were measured at baseline, at the end of each 4-week treatment period and at the 2-week wash-out period. Susceptibility of low-density lipoprotein (LDL) particles to oxidation, a marker of oxidative stress, was determined in 11 patients at random before and after 4-week treatment of oral L-arginine. We demonstrates that consumption of either L-arginine or vitamin C significantly increased brachial artery flow-mediated dilatation (mean diameter change from baseline of 4.87%, P<0.0001 and of 3.17%, P=0.0003, respectively). Neither oral L-arginine nor vitamin C affected lipid profiles and circulating levels of inflammatory markers. However, in the 11 patients whose LDL susceptibility to oxidation was determined, lag time significantly increased by 27.1% (P=0.045) after consumption of L-arginine for 4 weeks. Oral L-arginine supplement improved endothelial function and reduced LDL oxidation in stable CAD patients.

Increased Susceptibility of Low-Density Lipoprotein to Ex Vivo Oxidation in Mice Transgenic for Human Apolipoprotein B Treated with 1 Melatonin-Related Compound Is Not Associated with Atherosclerosis Progression

Considerable evidence supports the hypothesis that LDL oxidation has an important role in atherosclerosis. It has been demonstrated that the feeding of hypercholesterolemic mice on an atherogenic diet supplemented with melatonin highly increases the surface of atherosclerotic lesions in aorta and the sensitivity of atherogenic lipoprotein to ex vivo oxidation even though high melatonin doses inhibit lipoprotein oxidation in vitro. A melatonin-related compound (DTBHB: N-[2-(5-methoxy-1H-indol-3-yl)ethyl]-3,5-di-tert-butyl-4-hydroxybenzamide) has been reported to strongly inhibit lipid peroxidation in vitro. In the present study, DTBHB treatment considerably increased the sensitivity of atherogenic lipoproteins to ex vivo oxidation but did not modify atherosclerotic lesion development in mice. Moreover, DTBHB treatment did not induce detectable lipidic alteration. These data confirm that the capacity of molecules to inhibit atherogenic lipoprotein oxidation in vitro offers no prediction of their capacity to inhibit in vivo atherosclerosis development.

Weight loss associated with reduced intake of carbohydrate reduces the atherogenicity of LDL in premenopausal women

The effect of a 3-tier intervention including dietary modifications (ie, moderate energy restriction, decreased carbohydrate, increased protein), increased physical activity, and the use of carnitine as a dietary supplement was evaluated on plasma lipids and the atherogenicity of low-density lipoprotein (LDL) particles in a population of overweight and obese premenopausal (aged 20-45 years) women. Carnitine or a placebo (cellulose) was randomly assigned to the participants using a double-blind design. Carnitine supplementation was postulated to enhance fat oxidation resulting in lower concentrations of plasma triglycerides. Seventy women completed the 10-week protocol, which followed a reduction in their energy intake by 15% and a macronutrient energy distribution of 30% protein, 30% fat, and 40% carbohydrate. In addition, subjects increased the number of steps taken per day by 4500. As no differences were observed between the carnitine and placebo groups in all the measured parameters, all subjects were pooled together for statistical analysis. Participants decreased ( P < .01) their caloric intake (between 4132.8 and 7770 kJ) and followed prescribed dietary modifications as assessed by dietary records. The average number of steps increased from 8950 ± 3432 to 12 764 ± 4642 ( P < .001). Body weight, plasma total cholesterol, LDL cholesterol, and triglyceride were decreased by 4.5%, 8.0%, 12.3%, and 19.2% ( P < .0001), respectively, after the intervention. Likewise, apolipoproteins B and E decreased by 4.5% and 15% ( P < .05) after 10 weeks. The LDL mean particle size was increased from 26.74 to 26.86 nm ( P < .01), and the percent of the smaller LDL subfraction ( P < .05) was decreased by 26.5% ( P < .05) after 10 weeks. In addition, LDL lag time increased by 9.3% ( P < .01), and LDL conjugated diene formation decreased by 23% ( P < .01), indicating that the susceptibility of LDL to oxidation was decreased after the intervention. This study suggests that moderate weight loss (<5% of body weight) associated with reduced caloric intake, lower dietary carbohydrate, and increased physical activity impacts the atherogenicity of LDL.

Increased Low-Density Lipoprotein Susceptibility to Oxidation in Pregnancies and Fetal Growth Restriction

Atherosis and placental infarction have been observed in pregnancies complicated by fetal growth restriction (FGR). Low-density lipoprotein (LDL) oxidation plays a central role in the pathogenesis of atherosclerosis; therefore, it could be involved in the placental alterations observed in FGR. The aims of the present study were to estimate LDL susceptibility to oxidation in pregnancies complicated by FGR and to evaluate their relationship with fetal growth and placental hormone secretion. A cohort prospective study was carried out in 50 women with uncomplicated pregnancies and 55 women with FGR. Blood was drawn at 15, 24, and 32 weeks of gestation. Low-density lipoprotein oxidation was initiated by the addition of CuCl2 and formation of conjugated dienes was monitored. Cholesterol, triglycerides, vitamin E, estradiol, progesterone, and placental lactogen were determined. Women with FGR showed a lag phase (minutes from addition of CuCl2) similar to the control group in the first trimester of pregnancy (85.3 +/- 3.3 versus 81.3 +/- 5.6). But in the second and third trimester, they showed a lower lag phase than the control group: 69.6 +/- 3.6 versus 84.4 +/- 3.5 (P < .05) and 69.9 +/- 3.4 versus 95.6 +/- 3.4 (P < .001). During the third trimester, pregnancies complicated with FGR showed lower levels of estradiol, progesterone, and human placental lactogen than those in the control group. In the third trimester, a positive correlation was found between the lag phase and the birth weight (P = .001) and with the plasma levels of estradiol (P = .002). Fetal growth restriction is associated with an increased LDL susceptibility to oxidation, a process that could damage the placenta, leading to alterations in placental endocrine function and fetal weight. Pregnancies complicated by fetal growth restriction show an increased LDL susceptibility to oxidation, a process that may lead to placental dysfunction and growth delay.

Effects of estrogen-only therapy on LDL oxidation in women with hysterectomy: Does paraoxonase genotype play a role?

Objectives This study investigated the effects of estrogen-only therapy on lipid profile (through susceptibility of low density lipoproteins to oxidation) and on oxidant-antioxidant parameters in surgical menopausal women. PON genotypes are also evaluated considering that they may be associated with the personal differences observed in antioxidant effects induced by estrogen. Methods Thirty women who had undergone hysterectomy + bilateral ovariectomy in the last 3 years, with causes other than malignancy were included and given estrogen-only (Premarin-Wyeth Inc. 0.625 mg/day/6 months, equine conjugated estrogen). Blood samples were collected at baseline, first and sixth month of treatment. Serum (total antioxidant activity-TAO and PON activity), erythrocyte (TBARS and catalase activity), LDL and Cu 2+ induced ox-LDL (TBARS and diene levels) samples were evaluated and PON1 192 polymorphisms were determined by PCR amplification & restriction enzyme digestion. Results At the sixth month, a higher TAO activity ( p = 0.016) and a lower eTBARS ( p = 0.028) were detected compared to the basal values. LDL and Cu induced ox-LDL TBARS levels at the sixth month of treatment were significantly ( p = 0.012 and 0.026, respectively) lower compared to the pretreatment values. Baseline eTBARS ( p = 0.007), LDL TBARS ( p = 0.044) and eCAT ( p = 0.033) activities were significantly higher in homozygote Q allele carriers compared to subjects with R allele. LDL TBARS and Cu 2+ induced ox-LDLTBARS of QQ subjects ( p = 0.018 and 0.050) as well as LDL TBARS of QR subjects ( p = 0.044) showed a significant decrease with estrogen-only treatment. Conclusions Our study drives the attention to PON polymorphism in postmenopausal women who have risk for atherosclerosis. Although our data is limited, this study is the first that focuses on the role of PON genotypes in antiatherosclerotic effects of estrogen-only and provides important points for further studies.

Protective effect of dietary capsaicin on induced oxidation of low-density lipoprotein in rats

An animal study was carried out to examine the beneficial influence of the known hypocholesterolemic spice principle-capsaicin on the susceptibility of low-density lipoprotein to oxidation in normal and hypercholesterolemic condition. In rats rendered hypercholeterolemic by maintaining them on a cholesterol-enriched diet for eight weeks, inclusion of capsaicin (0.015%) in the diet, produced significant hypocholesterolemic effect. Oxidation of low-density lipoprotein was induced either by copper ion in vitro after its isolation, or by ferrous ion in vivo in experimental rats under either normal or hypercholesterolemic situation and the beneficial effect of dietary capsaicin on the same was evaluated. LDL oxidation was measured by the thiobarbituric acid reactive substances (TBARS) formed and relative electrophoretic mobility of oxidized LDL. Dietary capsaicin was found to be protective to the LDL oxidation in vitro in the case of normal rats as indicated by reduction in TBARS by more than 40%. In the case of LDL isolated from hypercholesterolemic rats the extent of copper induced LDL oxidation was significantly lower than that of LDL isolated from normal rats. Dietary capsaicin did not make any difference in the extent of LDL oxidation in vitro in hypercholesterolemic rats. Ferrous ion induced in vivo oxidation of LDL was 71% lower in capsaicin fed normal rats. In high cholesterol feeding, Fe-induced in vivo oxidation of LDL was 73% lower, while the same was still marginally lower in capsaicin fed hypercholesterolemic rats. Hepatic lipid peroxidation was significantly decreased by dietary capsaicin in normal rats. While a significantly decreased level of lipid peroxidation was observed in hypercholesterolemic rats compared to normal rats, the same was not significantly altered by dietary capsaicin. Results suggest that dietary spice principle capsaicin is protective to LDL oxidation both in vivo and in vitro under normal situation, while in hypercholesterolemic situation where the extent of LDL oxidation is already lowered, capsaicin does not offer any further reduction.

Changes in plasma antioxidant capacity and oxidized low-density lipoprotein levels in men after short-term cranberry juice consumption

Low-density lipoprotein (LDL) oxidation is closely implicated in the development of atherosclerotic cardiovascular disease (CVD), and thus, reducing LDL susceptibility to oxidation with antoxidants could be of importance in CVD prevention. Flavonoids, polyphenolic compounds found in a large selection of fruits and vegetables, have been characterized as having a strong antioxidant potential, and intake of flavonoid-rich foods has been related to decreased morbidity and mortality from heart disease. The present study was therefore undertaken to investigate the effect of flavonoid-rich cranberry juice supplementation on plasma lipoprotein levels and LDL oxidation. For that purpose, 21 men (age ± SD, 38 ± 8 years) were enrolled in a 14-day intervention and instructed to drink cranberry juice 7 mL/kg body weight per day. Physical and metabolic measures including plasma lipid and oxidized LDL (OxLDL) concentrations as well as antioxidant capacity were performed before and after the intervention. At baseline, we found that plasma OxLDL levels were significantly associated with waist circumference ( r = 0.47, P = .0296) as well as plasma triglyceride ( r = 0.68, P = .0007) and apolipoprotein B ( r = 0.91, P < .0001) concentrations. The intervention led to a reduction in plasma OxLDL levels (−9.9% ± 17.8%, P = .0131) and increase in antioxidant capacity (+6.5% ± 10.3%, P = .0140). However, no relationship was found between both of these changes ( r = −.01, not significant). The intervention did not result in any improvement of plasma lipoprotein-lipid or inflammatory marker concentrations. Our results show that short-term cranberry juice supplementation is associated with significant increase in plasma antioxidant capacity and reduction in circulating OxLDL concentrations. Although the physiological relevance of our observations needs to be further examined, our study supports the potential role of antioxidant-rich foods in maintaining health and preventing CVD.

Effects of Glucose and α‐Tocopherol on Low‐Density Lipoprotein Oxidation and Glycation

Glycation of blood proteins is considered to be a major contributor to hyperglycemic complications in diabetes mellitus patients. In this study, we demonstrate the efficacy of alpha-tocopherol in reducing low-density lipoprotein (LDL) oxidation and glycation in vitro. Native LDL isolated from healthy subjects was exposed to various concentrations of glucose and malondialdehyde (MDA) with or without alpha-tocopherol enrichment for 7 days in sealed vacuum ampoules. The degree of glycation, copper-induced lag time, content of thiobarbituric acid-reactive substances (TBARS), and alpha-tocopherol levels in LDL were then assessed. LDL lag time was significantly reduced with high levels of glucose and MDA. Alpha-tocopherol enrichment dramatically inhibited the oxidation of LDL in the lag-time assay. However, the length of incubation time was inversely related to the LDL lag time. Longer incubation time resulted in shorter LDL lag time, with or without alpha-tocopherol enrichment. The level of TBARS associated with LDL oxidation was highest in native, MDA-supplemented, and high-glucose samples. The alpha-tocopherol levels were inversely related to glucose levels and incubation times. In conclusion, high-glucose concentrations heightened the oxidative susceptibility of LDL. Alpha-tocopherol enrichment reduced this trend and prevented LDL from undergoing architectural modification.

Insulin resistance, LDL particle size, and LDL susceptibility to oxidation in pediatric kidney and liver recipients

Dyslipidemia is common after solid organ transplantation. We have described hypertriglyceridemia in about 50% of our pediatric kidney, and in about 30% of our liver recipients. The aim of the present study was to find out whether this post-transplantation hypertriglyceridemia after pediatric solid organ transplantation is associated with insulin resistance and the occurrence of small, dense low-density lipoprotein (LDL). Fifty kidney and 25 liver recipients (aged 4 to 18 years) on triple immunosuppression, and 181 control children participated in the study for an average of 5.3 and 6.4 years after kidney and liver transplantation (range 1 to 11 years), respectively. Homeostasis model assessments for insulin resistance (HOMA) were calculated and fasting lipoprotein lipid profile, apolipoprotein A-I and B concentrations, LDL particle diameter, and indices of LDL susceptibility to copper-induced oxidation determined. Kidney patients had significantly higher serum total, high-density, and low-density lipoprotein cholesterol, triglyceride, apolipoprotein A-I and B concentrations than liver patients or control subjects (P < 0.003 for all). HOMA indices higher than the 95th percentile of Canadian normal children were seen in 50.0% of kidney (of liver 41.2%) recipients younger than 11 years, and in 27.3% of older recipients (of liver 37.5%). Smaller sized LDL or LDL of increased oxidizability was not more frequent in patients than in control children. Pediatric kidney recipients had significantly higher lipid and insulin concentrations than healthy control children. Combined hyperlipidemia and features of the dysmetabolic syndrome were common in children after kidney and liver transplantation. However, no small, dense LDL, or LDL prone to oxidation was seen in either group.

Polymorphonuclear Leukocytes May Impair Endothelial Function

To examine whether polymorphonuclear leukocytes (PMNs) in hypercholesterolemia (HC) are activated to generate large amount of superoxide in vivo and hence impair endothelial function and, if so, whether statins, which possess anti-inflammatory properties, may restore PMN-mediated endothelial dysfunction. At baseline, subjects with HC showed impaired endothelial function (P<0.001), estimated by flow-mediated vasodilation of the brachial artery, and increased susceptibility of low-density lipoprotein (LDL) to oxidation (P<0.0001) compared with control subjects. PMNs obtained from HC produced greater amount of superoxide (P<0.0001), showed higher adhesiveness to cultured endothelial cells (HUVECs) (P<0.0001), and impaired endothelial nitric oxide synthase (eNOS) Ser1177 phosphorylation of HUVECs compared with controls (P<0.001). Crossover administration of fluvastatin or colestimide for 3 months lowered LDL to the same levels (P<0.001 for both). Endothelial function was restored (P<0.0001). LDL oxidation (P<0.0001) and superoxide release from PMNs (P<0.0001) were diminished only in fluvastatin but not in colestimide arm. Fluvastatin attenuated PMN adhesion to HUVECs (P<0.0001) and restored eNOS Ser1177 phosphorylation of HUVECs (P<0.001). Statins may improve endothelial function at least in part by inactivating neutrophils independently of LDL reduction. Our results raise a novel concept that polymorphonuclear leukocytes may attack endothelia and play a pivotal role in the pathogenesis of atherosclerosis.