Plasma Lipid Peroxide Concentrations Research Articles

Does Increased Intake of Salmon Increase Markers of Oxidative Stress in Pregnant Women? The Salmon in Pregnancy Study

The Salmon in Pregnancy Study provided two meals of salmon per week to pregnant women from week 20 of gestation; the control group maintained their habitual diet low in oily fish. Salmon is a rich source of marine n-3 fatty acids. Since marine n-3 fatty acids may increase oxidative stress, we investigated whether increased salmon consumption could affect markers of oxidative stress in mid and late pregnancy. Urinary 8-iso-prostaglandin F(2α), urinary 8-hydroxy-2'-deoxyguanosine, and plasma lipid peroxide concentrations did not change from week 20 to 38 of pregnancy and were not altered by increased consumption of salmon. Thus, increased intake of salmon during pregnancy does not increase oxidative stress, as judged by the markers of oxidative damage to lipids and DNA measured herein.

Increased lipid peroxidation in adult GH-deficient patients: Effects of short-term GH administration

Adult GH deficiency (GHD) syndrome is characterized by increased risk of atherosclerosis and hence of cardio- and cerebrovascular mortality. Oxidative stress appears to play an important role in early atherogenesis. Oxidized LDL represents an important predictor of cardiovascular risk and is mainly responsible for oxidative damage of the endothelium. Its concentrations are increased in GHD, but the association between this abnormality and oxidative stress is still unclear, due to the discordant results yielded by the few available studies. In 13 GHD patients, plasma lipid peroxide concentrations were measured before and after a 4-month treatment with recombinant human GH (rhGH) and compared with those of 13 age- and sex-matched controls. In the same subjects, the so-called "lag-time", an index of anti-oxidant activity and thus of plasma oxidative balance, was also measured using a fluorescence kinetics method. Before treatment, peroxide levels were significantly higher in patients than in controls (374.0+/-31.52 vs 268.0+/-8.51 U.C., p<0.01), whereas the lag-time was significantly lower (113.0+/-10.70 vs 168.0+/-7.80 min, p<0.01). RhGH administration to patients resulted both in a significant decrease in lipid peroxide levels (from 374.0+/-31.52 to 336.0+/-33.17 U.C., p<0.01) and a significant prolongation of lag-time (from 113.0+/-10.70 to 144.0+/-15.00 min, p<0.01). After treatment, both parameters were no longer significantly different in patients and controls. Lag-time and peroxide levels at baseline did not show any correlation with IGF-I concentrations in GHD patients. After replacement therapy, however, lag-time was positively (r2= 0.62, p<0.01), and peroxide levels negatively (r2=0.41, p<0.05), correlated with IGF-I levels. These data support the view that adult GHD syndrome is characterized by an unbalance between pro- and anti-oxidant factors with marked preponderance of the former. This abnormality, likely contributing to the increased atherogenic risk of GHD patients, is corrected by short-term GH administration at a dose able to increase, although not to fully normalize, IGF-I levels.

Relationship between Isoprostane Concentrations, Metabolic Acidosis, and Morbid Neonatal Outcome

When a fetus is subjected to a massive perinatal hypoxic-ischemic insult, it may suffer sufficient damage to cause intrauterine death and stillbirth (1)(2)(3)(4)(5). In less severe, nonfatal cases, prolonged or severe intrauterine hypoxia may lead to serious neonatal complications such as hypoxic-ischemic encephalopathy (HIE), cerebral palsy, and impaired myocardial function (6)(7)(8). Hypoxia during labor leads to anaerobic respiration in the fetus and an accumulation of lactic acid in the tissues, producing metabolic acidosis. Damage to the brain and heart in asphyxia neonatorum is not a direct result of hypoxia, but rather of the toxic effects of reactive oxygen species generated after reperfusion of ischemic tissues. We have demonstrated that lipid peroxidation in the fetus increases during normal labor (9) and that umbilical cord plasma lipid peroxide concentrations are higher in situations known to lead to intrapartum hypoxia (10)(11)(12) and much lower after elective cesarean delivery (13). Reperfusion of damaged organs with oxygenated blood after delivery may also be detrimental to the infant’s long-term survival. Prediction of long-term neurodevelopmental outcomes in infants with birth asphyxia remains challenging. Unfortunately, previous studies have shown that clinical and biochemical variables, such as umbilical artery blood gases or Apgar scores, are of limited value in predicting morbid neonatal outcome. We have proposed the use of lipid peroxidation products, acting as footprints of oxidative stress, as alternative measures of perinatal outcome (14). Increased concentrations of lipid peroxidation products in cord arterial blood are associated with clinical situations known to cause fetal distress, but they have not been shown to be associated with significant morbid outcomes such as HIE. This study aims to demonstrate an association between increased umbilical cord blood lipid peroxide concentrations and morbid neonatal outcomes. The study hypotheses …

The effect of pre-germinated brown rice intake on blood glucose and PAI-1 levels in streptozotocin-induced diabetic rats.

Effects of pre-germinated brown rice (PGBR) on streptozotocin-induced diabetic rats were studied. The feeding of a PGBR diet to diabetic rats ameliorated the elevation of blood glucose and PAI-1 concentrations significantly, and tended to decrease the plasma lipid peroxide concentrations in comparison with rats fed a white rice diet. These results suggest that intake of PGBR instead of white rice is effective for the prevention of diabetic vascular complications.

Low density lipoprotein immunoapheresis does not increase plasma lipid peroxidation products in vivo

Extracorporeal elimination of low density lipoprotein (LDL) is frequently used in drug-resistant hypercholesterolemia. LDL-immunoapheresis selectively removes LDL and lipoprotein(a) [Lp(a)] from plasma. Lipid peroxidation is one unwanted side effect, that occurs during extracorporeal plasma treatment. The purpose of this study was to investigate the effect of LDL immunoapheresis on lipid peroxidation. Before and after a single LDL-immunoapheresis treatment, plasma concentrations of lipid hydroperoxides, determined with two different spectophotometric assays, thiobarbituric acid-reacting substances (TBARS), determined spectrophotometrically and malondialdehyde (MDA), determined by an MDA-TBA/HPLC method, were measured in 13 hypercholesterolemic patients. In addition MDA was also determined in the eluate of the apheresis column. Before treatment, plasma cholesterol and LDL cholesterol concentrations were significantly higher in patients than in healthy control subjects, as were the lipid peroxidation products. LDL-immunoapheresis treatment of the patients led to significant decreases in total cholesterol (69±8%), LDL-cholesterol (79±7%), HDL-cholesterol (35±17%), triglycerides (38±21%), apolipoprotein-B (77±6%), apolipoprotein-A1 (25±5%) and Lp(a) concentrations (76±10%). Changes in plasma lipid peroxide concentrations (17±8 nmol/l before vs. 14±5 nmol/l after treatment) were not significant, neither were those in TBARS (3.0±2.6 μmol/l vs. 2.3±1.3 μmol/l) or MDA concentrations (1.03±0.17 μmol/l vs. 1.0±0.20 μmol/l). Patients with high baseline values showed a decrease, whereas others did not. MDA was present (0.57±0.13 μmol/l) in the eluate of the apheresis column, suggesting that, along with LDL, lipid peroxidation products are also removed. From these results we conclude that a single LDL-immunoapheresis treatment effectively reduces LDL and Lp(a) in the absence of increases in plasma lipid peroxidation products.

Coronary artery surgery is associated with different forms of atherogenic lipoprotein modifications

Background. Increasing evidence shows that thrombogenicity and atherogenicity of lipoproteins are related to modifications involving oxidative, enzymatic, or physical alterations of these molecules. Findings on lipid peroxidation associated with cardiopulmonary bypass are conflicting, and the possible other forms of atherogenic lipid modification are unknown. The various forms of lipoprotein modifications including lipid peroxidation, desialylation, and leukocytic elastase activity after coronary artery bypass graft operations are examined. Methods. In patients undergoing coronary artery bypass graft operations, plasma total lipid hydroperoxides (n = 102), plasma leukocytic elastase activity (n = 125), free radical formation (n = 30), low-density lipoprotein oxidation, and sialic acid content before operation and at 2, 24, 48, and 72 hours after cardiopulmonary bypass and 3 months after operation were measured. Results. Preoperative plasma lipid peroxide concentration (2.2 μmol/L) increased after cardiopulmonary bypass (peak, 7.5 μmol/L; p < 0.001) and remained significantly elevated at 3 months after surgery (4.2 μmol/L; p < 0.01). There was a significant correlation between increased free radical generation and lipid peroxide levels in blood at all postoperative intervals. Low-density lipoprotein separated from plasma samples showed increased oxidation 48 hours after bypass. Sialic acid content of low-density lipoprotein was significantly reduced 48 hours after bypass. Plasma elastase activity increased significantly at all postoperative intervals. Conclusions. Coronary artery bypass graft operation is associated with generation of sustained blood levels of modified lipoproteins. These thrombogenic and atherogenic particles may play an important role in hemostatic and arteriosclerotic complications of coronary artery bypass graft operations.

Supplementation with vitamins C and E enhances cytokine production by peripheral blood mononuclear cells in healthy adults

The effect of supplementation with vitamins C and E on cytokine production of healthy adult volunteers was studied in a single-blind trial. Ten subjects in each group received daily vitamin C (1 g ascorbic acid), vitamin E (400 mg dl-alpha-tocopheryl acetate), or vitamins C and E for 28 d. Plasma concentrations of alpha-tocopherol, ascorbate, and lipid peroxides as well as the production of cytokines by peripheral blood mononuclear cells (PBMCs) were measured before, during, and at the end of the supplementation and 1 wk later. PBMCs were cultured in the presence of absence of lipopolysaccharide for 24 h. The interleukin 1 (IL-1), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) in the culture supernates were assayed by enzyme-linked immunosorbent assay methods. Production of IL-1 beta and TNF-alpha in the group supplemented with vitamins C and E was significantly higher (P < 0.05) than that of the groups given vitamin E or vitamin C alone. The enhancing effect of supplementation with a combination of vitamins E and C coincided with peak plasma alpha-tocopherol and ascorbate concentrations and the lowest plasma lipid peroxide concentrations (P < 0.05) on day 14. In addition, an in vitro experiment with PBMCs showed that vitamins E and C reduced lipopolysaccharide-induced prostaglandin E2 production and enhanced TNF-alpha production. These results indicate that combined supplementation with vitamins C and E is more immunopotentiating than supplementation with either vitamin alone in healthy adults.

The nutritional effect of a-linolenic acid-rich emulsion with total parenteral nutrition in a rat model with inflammatory bowel disease.

The purpose of this study was to investigate the nutritional effect of perilla oil emulsion (POE) in a rat model with inflammatory bowel disease (IBD) induced by 2,4,6-trinitrobenzenesulfonic acid. POE and soybean oil emulsion (SOE) were infused at 20% of nonprotein energy during 7 days' total parenteral nutrition (TPN). After infusion of test solutions, body weight gain and cumulative nitrogen balance in the POE group were significantly higher than those in the fat-free TPN (FF) group after infusion of test solutions. Moreover, those in the POE group were higher than those in the SOE group, but no significant difference was observed between the POE and SOE groups. In the POE group, total cholesterol and phospholipid concentration in the plasma was significantly decreased compared with the FF and SOE groups. Triglyceride concentration in the plasma did not significantly differ between the POE, SOE and FF groups. Plasma lipid peroxide concentration in the POE group was significantly lower than that in the SOE group, but it was not different from the FF group. In fatty acid composition in the plasma total lipids, linoleic acid in the POE and SOE groups and alpha-linolenic acid in the POE group were significantly increased compared with those in the FF group. Arachidonic acid (AA) in the POE and FF groups were significantly decreased compared with that in the SOE group. Otherwise, eicosapentaenoic acid (EPA) in the POE group was significantly increased compared with that in the SOE and FF groups. EPA/AA ratio in the POE group was significantly increased compared with the SOE group. The thickness and damage score of the colon were significantly depressed in the POE group compared with the SOE group. These results suggest that POE has a superior nutritional effect and improves inflammation in the IBD.

Lipid peroxidation of circulating low density lipoproteins with age, smoking and in peripheral vascular disease

In this study, lipid peroxides in plasma and the low density lipoprotein (LDL) fraction and plasma concentrations of vitamin E, lipids and lipoproteins were measured in 22 smokers (mean age 35 years), 26 non-smoking patients with peripheral vascular disease (PVD, mean age 66 years), and 23 younger (ages ⩽55 years) and 26 older (ages > 55 years) healthy subjects. Plasma lipid peroxide concentrations in the PVD patients (105.9 ± 20.6 vs. 91.8 ± 15.8 ng malondialdehyde (MDA)/ml plasma, mean ± S.D.) and the smokers (94.1 ± 16.5 vs. 74.0 ± 13.9 ng MDA/ml plasma) were significantly elevated compared with levels in the appropriate control subjects and levels were significantly higher in older compared with younger control subjects. Plasma LDL lipid peroxides were also significantly raised in patients with PVD and smokers compared with control values (PVD: 37.1 ±7.7 vs. 26.3 ± 4.1 ng MDA/ml plasma; smokers: 30.4 ± 6.9 vs. 24.9 ± 7.5 ng MDA/ml plasma). The ratio of LDL lipid peroxides:LDL-cholesterol was significantly higher in the smokers, and plasma cholesterol and LDL-cholesterol were significantly higher in patients with PVD compared with other groups of subjects. The ratio of vitamin E:total lipid was not significantly different between the study groups. These data show that lipid peroxide levels in the plasma LDL fraction are elevated along with raised circulating levels in patients with PVD and smokers but that LDL lipid peroxide concentrations were independent of age in the healthy subjects. Elevated LDL lipid peroxide concentrations may be mainly due to abnormally high LDL levels in PVD patients, whereas in smokers, the concentration of lipid peroxides in the LDL particles is raised and might render the lipoprotein more atherogenic.

Oxidized lipids in insulin-dependent diabetes mellitus: A sex-diabetes interaction?

The increased cardiovascular risk experienced by patients (particularly women) with insulin-dependent diabetes mellitus (IDDM) is not fully explained by conventional risk factors including lipid and lipoprotein concentrations. To determine if plasma lipid peroxide concentrations are relevant to these observations, levels of thiobarbituric acid reactive substances (TBARS) were measured in 56 young adult subjects with IDDM (mean age, 33 years; duration, 24 years) and 56 age- and sex-matched healthy controls. The TBARS concentration was significantly higher in women with diabetes than in female controls (7.4 v 4.5 nmol/mL, P = .001), but not in men with IDDM (5.1 v 5.3 nmol/mL). Diabetic men showed a significant correlation between triglyceride and TBARS concentrations ( P < .01), a finding not seen in diabetic women. Furthermore, there was a correlation between glycemic control (hemoglobin A 1 [HBA 1]) and TBARS in diabetic men, but not in women ( P < .01). These findings raise the possibility that the relatively greater increase in cardiovascular disease risk seen in IDDM women compared with men may relate to their increased degree of lipid peroxidation, which is independent of their degree of glycemic control.

Dietary Ascorbic Acid Depresses Plasma and Low Density Lipoprotein Lipid Peroxidation in Genetically Scorbutic Rats

The effects of dietary ascorbic acid on plasma lipoprotein and liver lipid peroxide concentrations were examined using ODS od/od rats with a genetic defect in the ability to synthesize ascorbic acid. ODS od/od rats were fed purified diets supplemented with 0 to 300 mg ascorbic acid/kg diet for 21 d. An ascorbic acid-free diet induced body weight loss, depleted ascorbic acid in the plasma and increased thiobarbituric acid-reactive substances in the plasma and liver as compared with rats fed ascorbic acid supplemented diets and with normal ODS +/+ rats fed the ascorbic acid-free diet. Increasing ascorbic acid concentration in the diet inhibited the development of these ascorbic acid deficiency symptoms in a dose-dependent manner. The dietary requirement of ascorbic acid to maintain normal body weight gain and plasma lipid peroxide concentrations was ∼150 mg ascorbic acid/kg diet. On the other hand, even 300 mg ascorbic acid/kg diet was insufficient to maintain a hepatic concentration of ascorbic acid comparable to that in the liver of ODS +/+ rats. The lipid peroxide concentration in plasma LDL and liver was significantly elevated in ODS od/od rats fed the ascorbic acid-free diet. Supplementing the diet with 300 mg ascorbic acid/kg kept those concentrations within the normal ranges seen in the ODS +/+ rats.

Levels of plasma lipid peroxides before and after choledocholithotomy in patients with obstructive jaundice.

Plasma lipid peroxide levels were measured in a group of 40 healthy controls and 11 patients with jaundice. In the case of these 11 patients, we checked the plasma lipid peroxide concentrations prior to and after choledocholithotomy. Before choledocholithotomy, there were significantly higher mean concentrations of plasma lipid peroxides and bilirubin in patients with jaundice than in the control cases (11.8 +/- 2.3 vs. 2.0 +/- 0.1 nmol/ml and 10.3 +/- 1.82 vs. 0.7 +/- 0.03 mg/dl, respectively, P < 0.05). In addition, patients with jaundice had lower plasma vitamin E levels in comparison to the controls (8.2 +/- 0.6 vs. 12.2 +/- 0.5 micrograms/ml, P < 0.05). In patients with jaundice, the increased plasma lipid peroxides were clearly related to the serum levels of bilirubin (r = 0.87, P < 0.05). After surgery, the higher plasma levels of lipid peroxide and bilirubin were reduced markedly (11.8 +/- 2.3 vs. 3.7 +/- 0.4 nmol/ml and 10.3 +/- 1.82 vs. 3.1 +/- 0.47 mg/dl, respectively, P < 0.05) with the restoration of bile flow which was associated with improvement in liver function tests. Consequently, these results suggest that there is an involvement of lipid peroxidation in liver cells damaged by obstructive jaundice in patients with cholelithiasis, and that these high plasma lipid peroxide levels may correlate with the severity of the disease.

Simple and specific test for measuring lipid peroxides in plasma.

The specificity of an iodometric assay for measuring lipid peroxides in lipoproteins was tested, compared with the fluorimetric thiobarbituric acid assay, and adopted for detecting lipid peroxide in plasma samples. Oxidation of low density lipoproteins in vitro by Cu2+, lipoxidase, and phagocytosing polymorphonuclear leucocytes was sensitively detected by the iodometric assay. Unlike the thiobarbituric acid assay, neither non-lipid substances commonly present in plasma, nor platelet or polymorphonuclear leucocyte by-products interfered with the iodometric assay. The iodometric assay measured a normal mean (SD) plasma lipid peroxide concentration of 10.8 (2.1) microM; n = 63. Two weeks after the start of a high cholesterol diet in rabbits (n = 5), a sixfold increase in plasma lipid peroxide concentrations was measured by iodometric assay. The specificity of a simple and sensitive iodometric test of lipid peroxidation was superior to that of the thiobarbituric acid assay. This iodometric assay should therefore provide a much more accurate assessment of lipid peroxide in plasma samples.

Lipid peroxides and atherosclerosis.

Plasma lipid peroxide concentrations were measured in 100 patients with occlusive arterial disease proved angiographically (50 patients with ischaemic heart disease, 50 with peripheral arterial disease) and compared with values in 75 control patients with no clinical evidence of atherosclerosis. Lipid peroxide concentrations were significantly higher in patients both with ischaemic heart disease (median 4.37 mumol/l (interquartile range 3.85-5.75 mumol/l); p less than 0.001) and with peripheral arterial disease (median 4.37 mumol/l (3.88-5.21 mumol/l); p less than 0.001) than in controls (median 3.65 mumol/l (interquartile range 3.29-3.89 mumol/l). Overall there was a significant but weak correlation between plasma lipid peroxide and plasma triglyceride concentrations (rs = 0.25; p less than 0.001) but not between plasma lipid peroxide and plasma total cholesterol concentrations. Furthermore, hypertension, obesity, diabetes, smoking, positive family history, and intake of beta blockers and thiazide diuretics were not associated with significant differences in lipid peroxide values. This study provides clinical support to experimental data indicating that peroxidised lipids may be important in atherogenesis and its complications and also suggests that peroxidised lipids may provide an index of the severity of atherosclerosis.

Studies on lipid peroxidation in biological systems. I. Effects on various factors on lipid peroxide level on blood.

Plasma lipid peroxide concentration has been demonstrated to vary with the species, strain, sex and age of laboratory animals as well as with conditions of starvation and stress. Mice showed remarkably high plasma TBA levels as compared with other species of animals, and the ICR and ddY strains of mice, among other strains, may be useful as experimental models, since they proved to have relatively slight interindividual differences. The data obtained indicate that great care in the management and experimental handling of laboratory animals are essential because of the enhancing effect of stress on the plasma TBA level.