Lipid Peroxidation In Humans Research Articles

A diet containing rapeseed oil-based fats does not increase lipid peroxidation in humans when compared to a diet rich in saturated fatty acids

A diet containing rapeseed oil-based fats does not increase lipid peroxidation in humans when compared to a diet rich in saturated fatty acids

The Superoxide Scavenger And Antioxidant, L-Propionyl-carnitine, Is Metabolically Enhanced Following Exercise In Hypoxia

L-Propionyl-carnitine, a propionyl ester of L-carnitine, is known to scavenge the superoxide anion, inhibit lipid peroxidation, and protect against H2O2-induced DNA strand scission. While exogenous L-propionyl-carnitine supplementation modulates lipid peroxidation in humans, the endogenous metabolic response following exercise is currently unknown. PURPOSE: To investigate the metabolic profile of L-propionyl-carnitine following exercise in hypoxia. METHODS: Twenty-four (n=24) apparently healthy male participants were recruited (age 28 ± 5 years; mass 74 ± 8 kg; stature 177 ± 6 cm; 2max hypoxia 45 ± 2 ml·kg-1·min-1: normoxia 60 ± 9 ml·kg-1·min-1), and completed 1 hr of exercise at a workload corresponding to 75% of pre-determined 2max in hypoxia (Fio2 = 0.16%), and repeated in normoxia (Fio2 = 0.21%). Serum L-propionyl-carnitine was quantified using a LC ESI-qTOF-MS untargeted metabolomics approach at pre-, post-exercise and 3 h post-exercise (Recovery). RESULTS: Exercise performed in hypoxia and normoxia independently increased L-propionyl-carnitine metabolism (p<0.05, pre vs. post-exercise), and hypoxia per se did not induce a selective metabolic change when compared to normoxia (p>0.05). Recovery from exercise was similar for both hypoxia and normoxia (p<0.05, post vs. 3 hrs post-exercise). There was a main effect for time observed for pooled hypoxia and normoxia values (pre vs. post-exercise vs. 3 hrs post-exercise, p<0.05). CONCLUSION: This is the first data to show a metabolic response in L-propionyl-carnitine following exercise. As such, we propose the increased mobilisation of L-propionyl-carnitine may be beneficial to counteract deleterious free radical production and protect against vascular exercise-induced oxidative stress.

A shortened treatment with rosemary tea (rosmarinus officinalis) instead of glucose in patients with diabetes mellitus type 2 (TSD).

Rosemary leaves powder has been reported to reduce in a dose-dependent manner, glucose levels, lipid profile and lipid peroxidation in humans. However, patients should ingest high doses of powder contained in capsules. This formulation constitutes the intake of 10 capsules per day, so the active metabolite must first, be released and then absorbed (for which, rosemary leaf powder must be mixed with gastric juice). Evaluate whether a shortened dose and time of treatment as well as the pharmaceutical presentation in rosemary tea (Rosmarinus officinalis) instead of powder have a therapeutic effect in the treatment of T2D. The complementary therapy with Rosemary tea (2g/1 litre of water per day) were evaluate on resistance to insulin, oxidative stress, biochemical parameters and anthropometric measurements in forty patients T2D under treatment with metformin and/or glibenclamide afther giving your authorization through informed consent. The data indicated that Rosemary tea intake after 90 days, statistically decreased (p < 0.05) anthropometric parameters like the body mass index and waist-hip ratio. Remarkably, this treatment decreased the percentages of glycated hemoglobin, insulin resistance, and the pancreatic β-cell function and lastly, a significant difference in lipid peroxide levels was found. These data show that shortening time and dose, as well as changing the formulation of the Rosemary plant constitutes a promising treatment for drug-resistant T2D patients.

Acute consumption of Black walnuts increases fullness and decreases lipid peroxidation in humans

Walnuts are a nutrient dense food, but most health research is on English walnuts (EW). Black walnuts (BW) contain a different antioxidant and fatty acid profile, and more protein, compared to EW. The purpose of the study was to compare postprandial responses following the consumption of 3 breakfast meals containing either butter (control), BW, or EW. We hypothesized that walnut-containing meals would mitigate post-meal increases in glucose, insulin, triglycerides, and lipid peroxidation while increasing TAC compared to the traditional meal without nuts. Furthermore, we hypothesized that the BW meal would exhibit greater TAC and subjective fullness while mitigating postprandial increases in lipid peroxidation better than the EW. This was a randomized, double-blind control crossover study in 30 healthy adults with three testing visits. At each visit, subjects consumed either the control, BW, or EW meal. Blood draws and visual analog scale appetite ratings were obtained at fasting, 30, 60, 120, and 180 min postprandially. The BW and EW meals resulted in greater suppression of appetite vs. control (P < .01 and P = .03, respectively), and the BW meal also increased fullness more than EW and control (P < .01 and P < .001, respectively). Finally, the BW meal also had a greater suppression of lipid peroxidation vs. control (P = .01). There were no other treatment differences in the other measures of appetite or for glycemia, triglycerides, or total antioxidant capacity. Substituting butter in a breakfast meal with BW or EW increased fullness; however, the BW meal was superior for suppressing overall appetite while also lowering postprandial lipid peroxidation.

Reinterpreting the best biomarker of oxidative stress: The 8-iso-PGF2α/PGF2α ratio distinguishes chemical from enzymatic lipid peroxidation

The biomarker 8-iso-prostaglandin F2α (8-iso-PGF2α) is regarded as the gold standard for detection of excessive chemical lipid peroxidation in humans. However, biosynthesis of 8-iso-PGF2α via enzymatic lipid peroxidation by prostaglandin-endoperoxide synthases (PGHSs), which are significantly induced in inflammation, could lead to incorrect biomarker interpretation. To resolve the ambiguity with this biomarker, the ratio of 8-iso-PGF2α to prostaglandin F2α (PGF2α) is established as a quantitative measure to distinguish enzymatic from chemical lipid peroxidation in vitro, in animal models, and in humans. Using this method, we find that chemical lipid peroxidation contributes only 3% to the total 8-iso-PGF2α in the plasma of rats. In contrast, the 8-iso-PGF2α levels in plasma of human males are generated >99% by chemical lipid peroxidation. This establishes the potential for an alternate pathway of biomarker synthesis, and draws into question the source of increases in 8-iso-PGF2α seen in many human diseases. In conclusion, increases in 8-iso-PGF2α do not necessarily reflect increases in oxidative stress; therefore, past studies using 8-iso-PGF2α as a marker of oxidative stress may have been misinterpreted. The 8-iso-PGF2α/PGF2α ratio can be used to distinguish biomarker synthesis pathways and thus confirm the potential change in oxidative stress in the myriad of disease and chemical exposures known to induce 8-iso-PGF2α.

Do n-3 polyunsaturated fatty acids increase or decrease lipid peroxidation in humans?

Abstract Background: Despite many known health benefits of n-3 polyunsaturated fatty acids (PUFA), there is a concern that their high degree of unsaturation may actually increase oxidative stress, lipid peroxidation (LPO), and chronic inflammatory diseases. In this review, we have analyzed results from published human studies regarding the effects of n-3 PUFA supplementation on markers of lipid peroxidation. Of the 22 published human studies, nine found no change, eight a decrease, and five an increase in markers of LPO. These inconsistencies may be due to methods, subject characteristics, dose, duration, fatty acid and antioxidant composition of supplements, and basal diets. METHODS used for analysis seem to be the most significant factor. Six of eight studies with a decrease in LPO determined F2-isoprostanes produced in vivo, and two determined plasma antioxidant capacity or hydroperoxides. n-3 PUFA can serve as scavengers for free radicals and also modulate expression of genes that determine the balance between oxidative and antioxidative status. Recent studies that monitored oxidation products of cholesterol and fatty acids support the hypothesis that n-3 PUFA decrease LPO. Most of the studies showing no change or increase in LPO determined markers that involved ex vivo sample preparation or oxidation (malondialdehyde, low-density lipoprotein oxidation, lipid hydroperoxides). A majority of studies do not indicate that n-3 PUFA increased LPO. Future studies need to investigate the effects of dose, duration, and composition of n-3 PUFA with standardized diets and methods on concentrations and types of LPO products produced.

Interference of Metals and Medications with the Detection of Lipid Peroxidation in Humans by Photometric TBARS Assay

The thiobarbituric acid (TBA) reaction with malondialdehyde (MDA) is commonly used to measure free radical- mediated oxidative changes in lipids containing polyunsaturated fatty acids (PUFA). This test has had a broad range of applications since it was introduced in 1949; among others, researchers have used this test to evaluate toxic outcomes of chemical exposure in many environmental and occupational settings. However, the test has been criticized because of its low specificity. It has been reported that several endogenous or exogenous compounds, including drugs and metals, may interfere with a photometric or fluorimetric assay. The wide use of this test in occupational toxicology to measure lipid peroxidation (LPO) in humans led us to investigate whether simultaneous medications with drugs or exposure to metals interfere with the assay. We show here that, in the presence of bismuth or medazepam, the test gives erroneous results in a spectrophotometric assay. Among the tested 45 compounds, bismuth inhibits the formation of the MDA-TBA complex. In contrast, medazepam caused 2-fold higher absorbance compared to the absorbance obtained in the absence of the drug. UV spectrum analysis revealed that another unknown product is formed with an absorption maximum of 458 nm. In addition, medazepam yielded a second product with TBA whose absorption spectrum was essentially identical to that of the MDA standard. We have succeeded in separating this product and quantifying the MDA-TBA complex accurately by a HPLC method. Though it requires more sophisticated equipment, we suggest using HPLC for MDA quantification in biological samples, which might contain potentially interfering compounds. Keywords: TBARS assay, malondialdehyde, interference, medazepam, bismuth, photometry, HPLC

Hexavalent chromium and its effect on health: possible protective role of garlic (Allium sativum Linn)

Hexavalent chromium or chromium (VI) is a powerful epithelial irritant and a confirmed human carcinogen. This heavy metal is toxic to many plants, aquatic animals, and bacteria. Chromium (VI) which consists of 10%-15% total chromium usage, is principally used for metal plating (H2Cr2O7), as dyes, paint pigments, and leather tanning, etc. Industrial production of chromium (II) and (III) compounds are also available but in small amounts as compared to chromium (VI). Chromium (VI) can act as an oxidant directly on the skin surface or it can be absorbed through the skin, especially if the skin surface is damaged. The prooxidative effects of chromium (VI) inhibit antioxidant enzymes and deplete intracellular glutathione in living systems and act as hematotoxic, immunotoxic, hepatotoxic, pulmonary toxic, and nephrotoxic agents. In this review, we particularly address the hexavalent chromium-induced generation of reactive oxygen species and increased lipid peroxidation in humans and animals, and the possible role of garlic (Allium sativum Linn) as a protective antioxidant.

Lipid Peroxidation in Workers Exposed to Aluminium, Gallium, Indium, Arsenic, and Antimony in the Optoelectronic Industry

The objective of this study was to investigate whether exposure to aluminum, gallium, indium, arsenic, and antimony induces lipid peroxidation in humans. Whole blood and urine levels of 103 exposed electronic industry workers and 67 referents were analyzed by use of inductively coupled plasma mass spectrometry. Malondialdehyde (MDA), the product of lipid peroxidation, was determined by high-performance liquid chromatography. The mean plasma MDA level in the 103 workers was significantly higher than that in 67 referents. The levels of MDA in the exposed workers were correlated significantly with the levels of urinary gallium and arsenic. Malondialdehyde as an index of lipid peroxidation can be induced by gallium and arsenic exposure. By reducing exposure to these metals, biologic effects such as lipid peroxidation may also be diminished.

Laser sensors for trace gases in human breath

Ethylene and ethane as biomarkers for lipid peroxidation in humans can be detected in the exhaled breath by means of very sensitive gas sensors based on high-resolution molecular spectroscopy. To this purpose, a laser photoacoustic spectroscopy sensor (PAS) for online ethylene monitoring and a tunable diode laser absorption spectroscopy sensor (TDLAS) for ethane detection were developed at ENEA Frascati Molecular Spectroscopy Laboratory. The sensors have been calibrated by certified mixtures. The main advantages of the breath analysis by spectroscopic technique are the high sensitivity and the absolutely non-invasive character. During an experimental study in cooperation with Umberto I Hospital (Radiology Institute) of Rome, we were able to detect very low concentrations (under 1 ppb) of trace ethylene content in the air exhaled by patients, following X-ray therapy; results are reported in this article.

Effects of vitamin C and aspirin in ischemic stroke‐related lipid peroxidation: Results of the AVASAS (Aspirin Versus Ascorbic acid plus Aspirin in Stroke) Study

A condition of oxidative stress is known to occur in ischemic stroke, the current therapeutic intervention of which is largely limited to thrombolysis. To assess the effect of vitamin C - in conjunction to aspirin - in ischemic stroke-related lipid peroxidation, we measured plasma levels of ascorbate, of 8,12-isoprostanes F2alpha-VI (8,12-iPF2alpha-VI) and activities and levels of a broad spectrum of antioxidant enzymes and micronutrients in stroke patients randomized to receive, from stroke onset and up to three months, either vitamin C (200 mg/day) plus aspirin (300 mg/day) or only aspirin (300 mg/day). By the end of the first week, patients treated with vitamin C plus aspirin had higher vitamin C levels (p = 0.02) and lower 8,12-iPF2alpha-VI levels (p = 0.01) than patients treated with aspirin alone. The significance was maintained for the increase of vitamin C after three months of therapy (p < 0.01). The clinical functional outcome for both groups of patients similarly ameliorated after three months of treatment. We conclude that vitamin C, at the dose of 200 mg/day and in conjunction with aspirin, significantly decreases ischemic stroke-related lipid peroxidation in humans. Further studies are warranted to clarify whether the use of vitamin C may add clinical long-term beneficial effects in patients with stroke.

Vitamin E supplementation, exercise and lipid peroxidation in human participants.

The theoretical benefits of using antioxidant vitamin supplements to quench oxygen free radicals appear large. The major function of vitamin E is to work as a chain-breaking antioxidant in a fat soluble environment so as to protect polyunsaturated fatty acids within membrane phospholipids and in plasma lipoproteins. The purpose of this critical review was to determine whether vitamin E supplementation decreases exercise-induced lipid peroxidation in humans. If vitamin E alone is ineffective, researchers can turn their efforts to other individual antioxidants or combinations. Using the search words "vitamin E", "exercise", "lipid peroxidation" and "antioxidant", all relevant studies since 1985 were identified through a computer search using Pub Med and Sport Discuss databases. Additional articles were reviewed from the reference list of the retrieved articles. Nine vitamin E studies met the criteria of using human participants in an experimental design. Studies were analyzed to determine the strength of evidence regarding the efficacy of vitamin E supplementation. Strength of evidence was based on: (1) number of participants, (2) intensity of the exercise test, (3) type of research design, (4) other controls, (5) the biomarker of lipid peroxidation, (6) the timing of the biomarker measurement, (7) measurement of vitamin E status and (8) correction for plasma volume change. Overall, the six studies showing no effect of vitamin E supplementation had a much higher total score (67) in comparison to the three studies showing positive effects (38). Although limitations have plagued much of the research, vitamin E supplementation does not appear to decrease exercise-induced lipid peroxidation in humans.

Periodic dip of lipidperoxidation in humans: a redox signal to synchronize peripheral circadian clocks?

The output generated by the endogenous circadian clock to control circadian functions and temporal organization in metazoans is unknown. Redox state perturbations generated by reactive oxygen species (ROS) and antioxidants are known to influence the expression of a number of genes and signal transduction pathways. Evidence has been recently provided that the reduced redox cofactors NAD and NADP both regulate clock gene activity in the suprachiasmatic nucleus (SCN) and are induced by it. Significant periodic variations of lipidperoxidation in human blood with a dip at 04.00 h have been previously reported. Such variations could be expected to alter the cellular redox state, thus possibly functioning as periodic redox signals from the master clock. To verify the existence of the mentioned variations the serum levels of malondialdehyde (MDA), a marker of lipidperoxidation, were monitored by High-Performance Liquid Chromatography in 39 healthy subjects at 3-h intervals over a 24-h period. Throughout the test period, only biological noise could be detected in all test persons. However, the normalized MDA levels at 03.00 h were significantly lower ( p <0.05 to <0.00005) in 38 (97%) of the cases and showed a significantly lower standard deviation ( p <0.004) than at any of the other 3-h intervals, indicating a periodic dip of lipidperoxidation (PDL) in diurnal active subjects. We hypothesize that the PDL, on the basis of its time of appearance, its frequency and its potential influence on cellular redox state, represents a periodic systemic redox output of the SCN, in terms of a relatively short and sudden interruption of the daily oxidative noise. According to recent research, it could be the result of redox alterations induced by the SCN activity and at the same time the pathway by which the master clock resets and synchronizes peripheral oscillators to the light/dark cycle. Additionally, the antioxidative function of the pineal gland activity postulated elsewhere could play a part in generating the described phenomenon. The PDL could be useful as a circadian phase marker in research dealing with treatment of jet lag and other sleep disorders.

Isomer-specific effects of conjugated linoleic acid on lipid peroxidation in humans: regulation by alpha-tocopherol and cyclo-oxygenase-2 inhibitor.

We have found previously that supplementation with conjugated linoleic acid (CLA) induces lipid peroxidation and inflammation in humans as indicated by an increase of 8-iso-prostaglandin F2alpha (PGF2alpha) and 15-keto-dihydro-PGF2alpha respectively. The present study was undertaken firstly to study the regulatory mechanisms behind these effects, and secondly to see if these effects are specific to different isomers of CLA. Sixty healthy men and women, divided into six groups, were given a cyclo-oxygenase (COX)-2 inhibitor (rofecoxib; 12 mg/day), alpha-tocopherol (200 mg/day) or neither treatment (control group) over a period of 6 weeks. During the last 4 weeks, three groups were given a CLA preparation (3.5 g/day) mainly containing the isomers cis-9, trans-11 and trans-10, cis-12 (CLA mix), and the three other groups a CLA preparation mainly containing the isomer trans-10, cis-12 (CLA 1012; 4.0 g/day). Treatment with alpha-tocopherol or COX-2 inhibitor did not alter the basal urinary levels of either 8-iso-PGF2alpha or 15-keto-dihydro-PGF2alpha. Both CLA preparations induced an increase in 8-iso-PGF2alpha and 15-keto-dihydro-PGF2alpha in the urine, with a larger increase being found in the CLA 1012 group. Treatment with the COX-2 inhibitor suppressed the increase in urinary 15-keto-dihydro-PGF2alpha in the CLA 1012 group, but not in the CLA mix group. Neither the COX-2 inhibitor nor alpha-tocopherol had any effect on 8-iso-PGF2alpha levels after supplementation with CLA. The CLA-induced production of PGF2alpha metabolites is probably partially mediated by COX-2. Levels of the induced lipid peroxidation may be dependent on the isomeric property of CLA.

Periodic dip of lipidperoxidation in humans: a redox signal to synchronize peripheral circadian clocks?

The output generated by the endogenous circadian clock to control circadian functions and temporal organization in metazoans is unknown. Redox state perturbations generated by reactive oxygen species (ROS) and antioxidants are known to influence the expression of a number of genes and signal transduction pathways. Evidence has been recently provided that the reduced redox cofactors NAD and NADP both regulate clock gene activity in the suprachiasmatic nucleus (SCN) and are induced by it. Significant periodic variations of lipidperoxidation in human blood with a dip at 04.00 h have been previously reported. Such variations could be expected to alter the cellular redox state, thus possibly functioning as periodic redox signals from the master clock. To verify the existence of the mentioned variations the serum levels of malondialdehyde (MDA), a marker of lipidperoxidation, were monitored by High-Performance Liquid Chromatography in 39 healthy subjects at 3-h intervals over a 24-h period. Throughout the test period, only biological noise could be detected in all test persons. However, the normalized MDA levels at 03.00 h were significantly lower ( p<0.05 to <0.00005) in 38 (97%) of the cases and showed a significantly lower standard deviation ( p<0.004) than at any of the other 3-h intervals, indicating a periodic dip of lipidperoxidation (PDL) in diurnal active subjects. We hypothesize that the PDL, on the basis of its time of appearance, its frequency and its potential influence on cellular redox state, represents a periodic systemic redox output of the SCN, in terms of a relatively short and sudden interruption of the daily oxidative noise. According to recent research, it could be the result of redox alterations induced by the SCN activity and at the same time the pathway by which the master clock resets and synchronizes peripheral oscillators to the light/dark cycle. Additionally, the antioxidative function of the pineal gland activity postulated elsewhere could play a part in generating the described phenomenon. The PDL could be useful as a circadian phase marker in research dealing with treatment of jet lag and other sleep disorders.

Application of gas chromatography-mass spectrometry for analysis of isoprostanes: their role in cardiovascular disease.

Cardiovascular disease (CVD) is the major cause of death in the Western hemisphere. Oxidative stress is involved in the pathophysiology of cancer, neurodegenerative conditions and CVD. Lipid peroxidation is one of the oxidative modifications possible in biological systems. The isoprostanes are derivatives of one specific lipid, i.e., arachidonic acid, after lipid peroxidation. Several isoprostanes have been identified in biological tissues and fluids, among them 8-iso prostaglandin F2alpha (8-iso-PGF2alpha, 8-epi-PGF2alpha, iPF2alpha-III, 15-F2t-IsoP) and its metabolite, 2,3-dinor-4,5-dihydro-8-iso-PGF2alpha. The isoprostanes are reliable in vivo markers of lipid peroxidation in humans: they are endogenously formed, characteristic in structure, ubiquitous in nature, stable in- and ex vivo and reliably quantitatable. In this Review, different analytical approaches will be discussed including immunologic, chromatographic and spectrometric techniques with the main emphasis on mass spectrometry. Analysis of isoprostanes applying radio immunoassay (RIA), enzyme immunoassay (EIA), high performance-liquid chromatography (HPLC), liquid chromatography-tandem mass spectrometry (LC-tandem MS), gas chromatography-mass spectrometry (GC-MS) and GC-tandem MS will be exemplified in the field of cardiovascular research. Results from several clinical studies are included indicating the validity of isoprostanes as surrogate parameters of oxidative stress in cardiovascular disease.

Regular Ingestion of Tea Does Not Inhibit In Vivo Lipid Peroxidation in Humans

Prospective studies suggest that tea may protect against cardiovascular disease. A potential mechanism for such an effect involves inhibition of lipid peroxidation by polyphenolic antioxidants derived from tea. Our objective was to determine whether regular ingestion of tea could inhibit in vivo lipid peroxidation. Two controlled intervention studies assessed the effects of regular ingestion of tea on lipid peroxidation determined by measurement of urinary F(2)-isoprostane excretion. Study 1: The effects of 1000 mL/d of green tea and black tea were compared with hot water containing caffeine in 13 subjects with elevated blood pressure using a randomized 3-period (7 d each) crossover design. Study 2: The effects of 1250 mL/d of black tea were compared with hot water in 22 subjects with mildly raised serum total cholesterol concentrations using a randomized 2-period (4 wk each) crossover design. F(2)-isoprostane excretion was not altered after regular ingestion of green tea (273 +/- 48 pmol/mmol creatinine) or black tea (274 +/- 39 pmol/mmol creatinine) in comparison with hot water (263 +/- 47 pmol/mmol creatinine; Study 1), or by regular ingestion of black tea (334 +/- 71 pmol/mmol creatinine) in comparison with hot water (355 +/- 75 pmol/mmol creatinine; Study 2). These results do not support the suggestion that polyphenolic antioxidants derived from tea inhibit in vivo lipid peroxidation.

Consumption of flavonoids in onions and black tea: lack of effect on F2-isoprostanes and autoantibodies to oxidized LDL in healthy humans

Oxidative damage to lipids in vivo may be involved in the development of atherosclerosis and cancer. Onions and black tea are foods rich in flavonoids, predominantly the flavonoid quercetin, which is a potent in vitro inhibitor of membrane lipid peroxidation and LDL oxidation. Our objective was to investigate the effects of consuming a high-flavonoid (HF) diet enriched with onions and black tea on indexes of oxidative damage in vivo compared with a low-flavonoid (LF) diet. Thirty-two healthy humans were studied in a randomized crossover design. Indexes of oxidative damage used were plasma F2-isoprostanes (a biomarker of lipid peroxidation in vivo) and the titer of antibodies to malondialdehyde (MDA)-modified LDL. There were no significant differences in the intake of macronutrients or assessed micronutrients, plasma F2-isoprostane concentrations, and MDA-LDL autoantibody titer between the HF and LF dietary treatments. In the men, however, plasma concentrations of the F2-isoprostane 8-epi-prostaglandin F2alpha were slightly higher after the HF treatment phase than after the LF treatment [0.31 +/- 0.029 nmol/L (111 +/- 10.4 ng/L) compared with 0.26 +/- 0.022 nmol/L (92 +/- 7.8 ng/L); P = 0.041]. In all subjects, plasma quercetin concentrations were significantly higher after the HF treatment phase than after the LF treatment: 221.6 +/- 37.4 nmol/L compared with less than the limit of detection of 66.2 nmol/L. Flavonoid consumption in onions and tea had no significant effect on plasma F2-isoprostane concentrations and MDA-LDL autoantibody titer in this study and thus does not seem to inhibit lipid peroxidation in humans.

Conjugated linoleic acid induces lipid peroxidation in humans

Conjugated linoleic acid (CLA) is shown to have chemoprotective properties in various experimental cancer models. CLA is easily oxidised and it has been suggested that an increased lipid oxidation may contribute to the antitumorigenic effects. This report investigates the urinary levels of 8-iso-PGF 2α, a major isoprostane and 15-keto-dihydro-PGF 2α, a major metabolite of PGF 2α, as indicators of non-enzymatic and enzymatic lipid peroxidation after dietary supplementation of CLA in healthy human subjects for 3 months. A significant increase of both 8-iso-PGF 2α and 15-keto-dihydro-PGF 2α in urine was observed after 3 months of daily CLA intake (4.2 g/day) as compared to the control group ( P<0.0001). Conjugated linoleic acid had no effect on the serum α-tocopherol levels. However, γ-tocopherol levels in the serum increased significantly ( P=0.015) in the CLA-treated group. Thus, CLA may induce both non-enzymatic and enzymatic lipid peroxidation in vivo. Further studies of the mechanism behind, and the possible consequences of, the increased lipid peroxidation after CLA supplementation are urgently needed.

Quantitative high performance liquid chromatography/tandem mass spectrometric analysis of the four classes of F(2)-isoprostanes in human urine.

Isoprostanes (iPs) are free radical catalyzed prostaglandin isomers. Analysis of individual isomers of PGF(2alpha)-F(2)-iPs-in urine has reflected lipid peroxidation in humans. However, up to 64 F(2)-iPs may be formed, and it is unknown whether coordinate generation, disposition, and excretion of F(2)-iPs occurs in humans. To address this issue, we developed methods to measure individual members of the four structural classes of F(2)-iPs, using liquid chromatography/tandem mass spectrometry (LC/MS/MS), in which sample preparation is minimized. Authentic standards of F(2)-iPs of classes III, IV, V, and VI were used to identify class-specific ions for multiple reaction monitoring. Using iPF(2alpha)-VI as a model compound, we demonstrated the reproducibility of the assay in human urine. Urinary levels of all F(2)-iPs measured were elevated in patients with familial hypercholesterolemia. However, only three of eight F(2)-iPs were elevated in patients with congestive heart failure, compared with controls. Paired analyses by GC/MS and LC/MS/MS of iPF(2alpha)-VI in hypercholesterolemia and of 8, 12-iso-iPF(2alpha)-VI in congestive heart failure were highly correlated. This approach will permit high throughput analysis of multiple iPs in human disease.