Stress oxydant chez l'enfant prématuré : causes, biomarqueurs et possibilités thérapeutiques [Oxidative stress after preterm birth: Origins, biomarkers, and possible therapeutic approaches].

The survival of preterm babies has increased over the last few decades. However, disorders associated with preterm birth, known as oxygen radical diseases of neonatology, such as retinopathy, bronchopulmonary dysplasia, periventricular leukomalacia, and necrotizing enterocolitis are severe complications related to oxidative stress, which can be defined by an imbalance between oxidative reactive species production and antioxidant defenses. Oxidative stress causes lipid, protein, and DNA damage. Preterm infants have decreased antioxidant defenses in response to oxidative challenges, because the physiologic increase of antioxidant capacity occurs at the end of gestation in preparation for the transition to extrauterine life. Therefore, preterm infants are more sensitive to neonatal oxidative stress, notably when supplemental oxygen is being delivered. Furthermore, despite recent advances in the management of neonatal respiratory distress syndrome, controversies persist concerning the oxygenation saturation targets that should be used in caring for preterm babies. Identification of adequate biomarkers of oxidative stress in preterm infants such as 8-iso-prostaglandin F2α, and adduction of malondialdehyde to hemoglobin is important to promote specific therapeutic approaches. At present, no therapeutic strategy has been validated as prevention or treatment against oxidative stress. Breastfeeding should be considered as the main measure to improve the antioxidant status of preterm infants. In the last few years, melatonin has emerged as a protective molecule against oxidative stress, with antioxidant and free-radical scavenger roles, in experimental and preliminary human studies, giving hope that it can be used in preterm infants in the near future.

Role of nitric oxide in genotoxicity: implication for carcinogenesis.

Reactive oxygen species can initiate carcinogenesis by virtue of their capacity to react with DNA and cause mutations. Recently, it has been suggested that nitric oxide (NO) and its derivatives produced in inflamed tissues could contribute to the carcinogenesis process. Genotoxicity of NO follows its reaction with oxygen and superoxide. It can be due either to direct DNA damage or indirect DNA damage. Direct damage includes DNA base deamination, peroxynitrite-induced adducts formation and single strand breaks in the DNA. Indirect damage is due to the interaction of NO reactive species with other molecules such as amines, thiols and lipids. The efficiency of one pathway or another might depend on the cellular antioxidant status or the presence of free metals.

FemHab: The effects of bed rest and hypoxia on oxidative stress in healthy women.

Independently, both inactivity and hypoxia augment oxidative stress. This study, part of the FemHab project, investigated the combined effects of bed rest-induced unloading and hypoxic exposure on oxidative stress and antioxidant status. Healthy, eumenorrheic women were randomly assigned to the following three 10-day experimental interventions: normoxic bed rest (NBR;n= 11; PiO2 = 133 mmHg), normobaric hypoxic bed rest (HBR;n= 12; PiO2 = 90 mmHg), and ambulatory hypoxic confinement (HAMB;n= 8: PiO2 = 90 mmHg). Plasma samples, obtained before (Pre), during (D2, D6), immediately after (Post) and 24 h after (Post+1) each intervention, were analyzed for oxidative stress markers [advanced oxidation protein products (AOPP), malondialdehyde (MDA), and nitrotyrosine], antioxidant status [superoxide dismutase (SOD), catalase, ferric-reducing antioxidant power (FRAP), glutathione peroxidase (GPX), and uric acid (UA)], NO metabolism end-products (NOx), and nitrites. Compared with baseline, AOPP increased in NBR and HBR on D2 (+14%; +12%;P< 0.05), D6 (+19%; +15%;P< 0.05), and Post (+22%; +21%;P< 0.05), respectively. MDA increased at Post+1 in NBR (+116%;P< 0.01) and D2 in HBR (+114%;P< 0.01) and HAMB (+95%;P< 0.05). Nitrotyrosine decreased (-45%;P< 0.05) and nitrites increased (+46%;P< 0.05) at Post+1 in HAMB only. Whereas SOD was higher at D6 (+82%) and Post+1 (+67%) in HAMB only, the catalase activity increased on D6 (128%) and Post (146%) in HBR and HAMB, respectively (P< 0.05). GPX was only reduced on D6 (-20%;P< 0.01) and Post (-18%;P< 0.05) in HBR. No differences were observed in FRAP and NOx. UA was higher at Post in HBR compared with HAMB (P< 0.05). These data indicate that exposure to combined inactivity and hypoxia impairs prooxidant/antioxidant balance in healthy women. Moreover, habitual activity levels, as opposed to inactivity, seem to blunt hypoxia-related oxidative stress via antioxidant system upregulation.

Increased oxidative stress markers may be a promising indicator of risk for primary ovarian insufficiency: a cross-sectional case control study

PURPOSE: The aim of this study was to evaluate serum levels of inducible nitric oxide synthase (INOS), myeloperoxidase (MPO), total antioxidant status (TAS), and total oxidative status (TOS) in women with primary ovarian insufficiency (POI) and to compare them with healthy fertile women. We also examined the possible risk factors associated with POI.METHODS: This cross-sectional case control study was conducted in Zekai Tahir Burak Women's Health Education and Research Hospital. The study population consisted of 44 women with POI (study group) and 36 healthy fertile women (control group). In all patients, serum levels of INOS, MPO, TAS, and TOS were determined. INOS and MPO levels were measured by enzyme-linked immunosorbent assay whereas colorimetric method was used for evaluating TAS and TOS levels. Age, body mass index (BMI), obstetric history, smoking status, family history, comorbidities, sonographic findings, complete blood count values, C-reactive protein and baseline hormone levels were also analyzed. Student's t-test or Mann-Whitney U test was used to compare continuous variables between the groups; categorical data were evaluated by using Pearson χ2 or Fisher exact test, when appropriate. Binary logistic regression method was used to identify risk factors for POI.RESULTS: We found significantly elevated levels of INOS (234.1±749.5 versus133.8±143.0; p=0.005), MPO (3,438.7±1,228.6 versus 2,481.9±1,230.1; p=0.001), and TOS (4.3±1.4 versus 3.6±1.4; p=0.02) in the sera of the study group when compared to the BMI-age matched control group. However, difference in serum levels of TAS were not significant between the 2 groups (1.7±0.2 versus 1.6±0.2; p=0.15). Logistic regression method demonstrated that BMI <25 kg/m2, nulliparity, family history of POI, smoking, and elevated serum levels of INOS, MPO, and TOS were independent risk factors for POI.CONCLUSION: We found an increase in INOS, MPO, and TOS in women with POI. These serum markers may be promising in early diagnosis of POI. Further large-scale studies are required to determine whether oxidative stress markers have a role in diagnosing POI.

Oxidative stress in the latissimus dorsi muscle of diabetic rats

The purpose of the present study was to investigate the effects of experimental diabetes on the oxidant and antioxidant status of latissimus dorsi (LD) muscles of male Wistar rats (220 ± 5 g, N = 11). Short-term (5 days) diabetes was induced by a single injection of streptozotocin (STZ, 50 mg/kg, iv; glycemia >300 mg/dl). LD muscle of STZ-diabetic rats presented higher levels of thiobarbituric acid reactive substances (TBARS) and chemiluminescence (0.36 ± 0.02 nmol/mg protein and 14706 ± 1581 cps/mg protein) than LD muscle of normal rats (0.23 ± 0.04 nmol/mg protein and 7389 ± 1355 cps/mg protein). Diabetes induced a 92% increase in catalase and a 27% increase in glutathione S-transferase activities in LD muscle. Glutathione peroxidase activity was reduced (58%) in STZ-diabetic rats and superoxide dismutase activity was similar in LD muscle of both groups. A positive correlation was obtained between catalase activity and the oxidative stress of LD, as evaluated in terms of TBARS (r = 0.78) and by chemiluminescence (r = 0.89). Catalase activity also correlated inversely with glutathione peroxidase activity (r = 0.79). These data suggest that an increased oxidative stress in LD muscle of diabetic rats may be related to skeletal muscle myopathy.

Short-term levosimendan treatment protects rat testes against oxidative stress

The objective of this study was to evaluate the effect of short-term levosimendan exposure on oxidant/antioxidant status and trace element levels in the testes of rats under physiological conditions. Twenty male Wistar albino rats were randomly divided into two groups of 10 animals each. Group 1 was not exposed to levosimendan and served as control. Levosimendan (12 µg/kg) diluted in 10 mL 0.9% NaCl was administered intraperitoneally to group 2. Animals of both groups were sacrificed after 3 days and their testes were harvested for the determination of changes in tissue oxidant/antioxidant status and trace element levels. Tissue malondialdehyde (MDA) was significantly lower in the levosimendan group (P < 0.001) than in the untreated control group and superoxide dismutase and glutathione peroxidase (GSH-Px) levels were significantly higher in the levosimendan group (P < 0.001). Carbonic anhydrase, catalase and GSH levels were not significantly different from controls. Mg and Zn levels of testes were significantly higher (P < 0.001) and Co, Pb, Cd, Mn, and Cu were significantly lower (P < 0.001) in group 2 compared to group 1. Fe levels were similar for the two groups (P = 0.94). These results suggest that 3-day exposure to levosimendan induced a significant decrease in tissue MDA level, which is a lipid peroxidation product and an indicator of oxidative stress, and a significant increase in the activity of an important number of the enzymes that protect against oxidative stress in rat testes.

Oxidative stress and cellular immunity in patients with recurrent aphthous ulcers

Recurrent aphthous ulcer (RAU) is an inflammatory condition of the oral mucosa characterized by painful, well-circumscribed, single or multiple round or ovoid ulcerations. The exact etiologic factor(s) of these ulcerations are not yet understood. The objective of this study was to evaluate inflammatory processes and free radical metabolism of 25 patients with RAUs compared to 25 healthy controls. The levels of malondialdehyde (MDA) and glutathione (GSH) were determined by high-performance liquid chromatography. Tumor necrosis factor-alpha (TNF-α), interleukin-2 (IL-2), IL-10, and IL-12 were determined by ELISA. Nitric oxide (NO), myeloperoxidase (MPO), total antioxidant status (TAS), and total oxidant status (TOS) levels were measured spectroscopically in serum. The levels of MDA, GSH, TNF-α, IL-2, IL-12, MPO, and TOS, and oxidative stress index (OSI) were higher, and the levels of NO, IL-10, and TAS were lower in patients with RAU than in controls. Statistical analysis showed that GSH, TNF-α, IL-2, IL-10, and OSI differed significantly in patients with RAU compared to controls. These parameters have important roles in oxidant/antioxidant defense.

Importance du stress oxydant dans le diabète secondaire à la fibrose kystique

Introduction : La fibrose kystique (FK) est une maladie génétique mortelle qui touche principalement les poumons et l’appareil digestif. Elle est causée par des mutations sur le gène codant la protéine du CFTR, un canal chlore exprimé à la surface des organes à sécrétions exocrines. Les fonctions principales du CFTR sont les suivantes: 1) la régulation de l’homéostasie ionique des sécrétions; 2) le maintien de la fluidité des sécrétions et; 3) le transport du glutathion. Le dysfonctionnement de la protéine du CFTR rend les sécrétions visqueuses et épaisses, avec des phénomènes obstructifs qui sont responsables de l’apparition de fibrose au sein des divers organes. Dans le poumon, l’accumulation du mucus épais rend difficile l’élimination des bactéries inhalées, ces dernières établissent alors des cycles d’infection qui endommagent les tissus pulmonaires à travers des processus inflammatoires. Dans le tube digestif, le mucus épais entrave l’absorption d’une quantité suffisante d’éléments nutritifs incluant les principaux antioxydants. L’infection et l’inflammation des poumons favorisent l’apparition d’un stress oxydant qui détruit davantage le tissu pulmonaire. Le déficit en glutathion, probablement lié au dysfonctionnement de la proteine du CFTR, et la malabsorption des antioxydants favorisent l’augmentation du stress oxydant. Une augmentation du stress oxydant a été démontrée au cours du diabète et les produits dérivés du stress oxydant ont été mis en évidence dans la pathogenèse des complications associées au diabète. Une augmentation du stress oxydant a également été montrée durant la FK, mais sans pour autant expliquer la survenue du diabète secondaire à la FK dont la prévalence augmente sans cesse. Objectifs : Notre étude consiste à évaluer l’impact du stress oxydant dans les anomalies du métabolisme du glucose durant la FK, et à étudier son rôle dans les mécanismes de sécrétion d’insuline induite par le glucose. Pour ce faire, nous avons déterminé l’impact de la peroxydation lipidique sur la tolérance au glucose et la défense antioxydante globale, in vivo, chez des patients FK présentant une altération du métabolisme du glucose. De plus, nous avons évalué le rôle du stress oxydatif sur la synthèse et la sécrétion d’insuline, in vitro, dans les cellules pancréatiques βTC-tet. Résultats : Dans l’étude in vivo, nous avons démontré que l’intolérance au glucose et le diabète étaient associés à une augmentation de la peroxydation lipidique, traduite par la hausse des niveaux sanguins de 4-hydroxynonenal lié aux protéines (HNE-P). La défense antioxydante évaluée par la mesure du glutathion sanguin démontre que les niveaux de glutathion oxydé restent également élevés avec l’intolérance au glucose. Dans l’étude in vitro, nos résultats ont mis en évidence que l’exposition de la cellule βTC-tet au stress oxydant: 1) induit un processus de peroxydation lipidique; 2) augmente la sécrétion basale d’insuline; 3) diminue la réponse de la sécrétion d’insuline induite par le glucose; et 4) n’affecte que légèrement la synthèse de novo de l’insuline. Nous avons aussi démontré que les cellules pancréatiques βTC-tet résistaient au stress oxydant en augmentant leur synthèse en glutathion tandis que la présence d’un antioxydant exogène pouvait restaurer la fonction sécrétoire de ces cellules. Conclusion : Le stress oxydant affecte le fonctionnement de la cellule pancréatique β de plusieurs manières : 1) il inhibe le métabolisme du glucose dont les dérivés sont nécessaires à la sécrétion d’insuline; 2) il active la voie de signalisation impliquant les gènes pro-inflammatoires et; 3) il affecte l’intégrité membranaire en induisant le processus de peroxydation lipidique.

Influence of Selected Dietary Micronutrient Elements on Growth and Biochemistry of Farmed Prawns

From the present study, it is clear that all the three metals, selenium, molybdenum and cobalt have significant effect on the antioxidant status of the shrimps. Selenium and molybdenum were observed to induce peroxidative damage at elevated levels. But at the same level, cobalt did not show such an effect. Selenium was found to be growth promoting at lower levels of dietary supplementation. Even though low levels of dietary selenium had a protective effect against the lipid peroxidation, the present study indicates that high levels of dietary selenium could promote lipid peroxidation. The selenium-dependent antioxidant enzyme, GPx behaved differently in muscle and hepatopancreas. A high concentration of selenium was required for the active expression of the enzyme in the muscle, where as in hepatopancreas maximum activity was observed at lower selenium concentration. Selenium supplementation had a positive effect on GSH concentration. The other antioxidant enzymes such as GST, SOD and CAT showed enhanced activity at higher concentration of selenium. Molybdenum supplementation significantly reduced the free radical scavenger enzymes SOD and CAT. This resulted in enhanced lipid peroxidation in tissues. The activity of antioxidant enzyme GPx and the concentration of the substrate for the enzyme, GSH also were lower at elevated levels of molybdenum supplementation. In addition to this amino acids and fatty acids were also altered in molybdenum supplemented groups. In trace amounts, dietary molybdenum exerts a beneficial effect on the growth and also in the activities of the enzymes XO and SO. At the same time it also indicates a possibility of oxidative damage as a result of the peroxidation caused by the activities of the enzymes SO and XO at elevated concentrations of molybdenum is also indicated. The absorption of various trace elements was also altered by molybdenum supplementation.Among the three metals studied, cobalt was the least toxic one at the administered levels. But this metal has a significant effect on the lipid content, amino acid composition, cholesterol levels and phospholipid levels. Increased growth was also observed as a result of cobalt supplementation in shrimps. The antioxidant system of the animal was activated by dietary cobalt. Tissue levels of the trace metals were also found to be altered in cobalt supplemented groups of shrimps.These studies, thus shows that influence of dietary trace metals calls for more detailed studies in farmed shrimp. They may hold the key to growth and even disease resistance in shrimp. But this still remains as a virgin field which demands more attention, especially in view of the increasing importance of shrimp farming.

Biochemical & Pharmacological evaluation of liver oils of selected deep sea sharks and chimaeras of the Indian EEZ

With a seacoast of 8,1 18 km, an exclusive economic zone (EEZ) of 2 million square km, and with an area of about 30,000 square km under aquaculture, lndia produces close to six million tonnes of fish, over 4 per cent of the world fish production. While the marine waters upto 50m depth have been fully exploited, those beyond, remain unexplored. There is an ever increasing demand for fishery resources as food. The coastal fishery resources of the country are dwindling at a rapid pace and it becomes highly imperative that we search for alternate fishery resources for food. The option we have is to hunt for marine fishery resources. Studies pertaining to proximate composition, amino acid and fatty acid composition are essential to understand the nutraceutical values of these deep sea fishery resources. The present study was aimed to carry out proximate composition of deep sea fishery resources obtained during cruises onboard the FORV Sarise Sampada, to identify fishery resources which have appreciable lipid content and thereby analyse the bioactive potentials of marine lipids, to study the amino acid profile of these fishery resources, to understand the contents of SPA, MUFA and PUFA and to calculate the n3/n6 fatty acid contents. Though the presence of nutraceuticals was identified in the marine fishery resources their use as potential food resources deserve further investigation. So the study were carried out to calculate the hepatosomatic indices of sharks & chimaeras and conduct biochemical characterisation of liver oils of Apristurus indicus, Cenlrophorus scalprams, Centroselachus crepidater, Neoharriotta raleighana, and Harriotta pinnata obtained during cruises onboard the FORV Sugar Sampada.Therapeutic use of shark liver oil is evident from its use for centuries as a remedy to heal wounds and fight flu (Neil er al. 2006). Japanese seamen called it 'samedava' or "cure all". Shark liver oil is being promoted worldwide as a dietary supplement to boost the immune system, fight infections, to treat cancer and to lessen the side effects of conventional cancer treatment. These days more emphasis is laid on the nutritive benefits of shark liver oils especially on the omega 3 polyunsaturated fatty acids ( PUFAs) (Anandan er al. 2007) and alkylglycerols (AKGs) (Pugliese er al. I998) contained in them due to the high rise of inflammatory disorders such as arthritis, asthma and neurodegenerative diseases like Alzheimer’s, Parkinson’s and Schizophrenia. So the present study also evaluate the pharmacological properties with respect to analgesic, anti-inflammatory, anti pyretic and anti-ulcer effects of four different liver oils of sharks belonging to the Indian EEZ and to identify the components of oil responsible for these activities.The analgesic and anti-inflammatory activities of liver oils from Neoharriotra raleighana (NR), Centrosymnus crepidater (CC), Apristurus indicus (AI), and Centrophorus sculpratus (CS) sharks caught from the Arabian Sea and the Indian Ocean were compared. The main objectives also include determination of the cholesterol lowering effects of liver oils of Neoharriotra raleighana (NR) and Centrophorus sculpratus (CS) on the high fat diet induced dyslipidemia and to compare the impact of four isolipidemic diets, on levels of serum diagnostic marker enzymes, on lipid profile of blood and liver and antioxidant status of heart in male Albino rats. And also to study the efficacy of Centrophorus sculpratus (CS) liver oil against Complete Freund’s Adjuvant-induced arthritis and to compare the anti-inflammatory activity of this oil with a traditionally used anti-inflammatory substance gingerol (oleoresin extracted from ginger.). The results of the present study indicated that both (Centrophorus sculpratus liver oils as well as gingerol extracts proved to be effective natural remedies against CFA-induced arthritis in Albino rats.

Supplementation with fruit and vegetable soups and beverages increases plasma carotenoid concentrations but does not alter markers of oxidative stress or cardiovascular risk factors

This study was aimed at determining whether an increase of 5 portions of fruits and vegetables in the form of soups and beverages has a beneficial effect on markers of oxidative stress and cardiovascular disease risk factors. The study was a single blind, randomized, controlled, crossover dietary intervention study. After a 2-wk run-in period with fish oil supplementation, which continued throughout the dietary intervention to increase oxidative stress, the volunteers consumed carotenoid-rich or control vegetable soups and beverages for 4 wk. After a 10-wk wash-out period, the volunteers repeated the above protocol, consuming the other intervention foods. Both test and control interventions significantly increased the % energy from carbohydrates and decreased dietary protein and vitamin B-12 intakes. Compared with the control treatment, consumption of the carotenoid-rich soups and beverages increased dietary carotenoids, vitamin C, alpha-tocopherol, potassium, and folate, and the plasma concentrations of alpha-carotene (362%), beta-carotene (250%) and lycopene (31%) (P < 0.01) and decreased the plasma homocysteine concentration by 8.8% (P < 0.01). The reduction in plasma homocysteine correlated weakly with the increase in dietary folate during the test intervention (r = -0.35, P = 0.04). The plasma antioxidant status and markers of oxidative stress were not affected by treatment. Consumption of fruit and vegetable soups and beverages makes a useful contribution to meeting dietary recommendations for fruit and vegetable consumption.

Effects of chronic and acute fruit and vegetable juice consumption on cardiovascular disease risk factors

Diets low in fruit and vegetables are reportedly responsible for 2.7 million deaths annually from cardiovascular diseases (CVD) and certain cancers. A daily fruit and vegetable intake of five 80 g portions is recommended for chronic disease prevention. However, in the UK, average adult consumption is less than three portions. It is suggested that fruit juice should only count as one portion. However, fruit juices are a beneficial source of phytochemicals. The preliminary results of two randomized, controlled, crossover, dietary intervention studies investigating the effects of chronic and acute consumption of fruit and vegetable puree and juice based drinks (FVPJ) on bioavailability, antioxidant status, vascular reactivity, and risk factors for CVD are reported. In the first study, 39 volunteers consumed 200 ml FVPJ, or fruit-flavoured control, daily for six weeks. In the second study, 24 volunteers consumed 400 mL FVPJ, or sugar-matched control, on the morning of the study day. Blood and urine samples were collected throughout both studies and real-time measurements of vascular tone were performed using laser Doppler imaging with iontophoresis. Overall, the studies showed that the fruit and vegetable puree and juice based drink increased dietary phytochemicals. There was a trend towards increased vasodilation following both acute and chronic fruit juice consumption. Measurements of antioxidant status, oxidative stress and other cardiovascular disease risk factors are currently being determined.

Effects of chronic and acute consumption of fruit- and vegetable-puree-based drinks on vasodilation, risk factors for CVD and the response as a result of the eNOS G298T polymorphism

The average UK adult consumes less than three portions of fruit and vegetables daily, despite evidence to suggest that consuming five portions daily could help prevent chronic diseases. It is recommended that fruit juice should only count as one of these portions, as juicing removes fibre and releases sugars. However, fruit juices contain beneficial compounds such as vitamin C and flavonoids and could be a useful source of dietary phytochemicals. Two randomised controlled cross-over intervention studies investigating the effects of chronic and acute consumption of commercially-available fruit- and vegetable-puree-based drinks (FVPD) on bioavailability, antioxidant status and CVD risk factors are described. Blood and urine samples were collected during both studies and vascular tone was measured using laser Doppler imaging. In the chronic intervention study FVPD consumption was found to significantly increase dietary carotenoids (P = 0.001) and vitamin C (P = 0.003). Plasma carotenoids were increased (P = 0.001), but the increase in plasma vitamin C was not significant. There were no significant effects on oxidative stress, antioxidant status and other CVD risk factors. In the acute intervention study FVPD were found to increase total plasma nitrate and nitrite (P = 0.001) and plasma vitamin C (P = 0.002). There was no effect on plasma lipids or uric acid, but there was a lower glucose and insulin peak concentration after consumption of the FVPD compared with the sugar-matched control. There was a trend towards increased vasodilation following both chronic and acute FVPD consumption. All volunteers were retrospectively genotyped for the eNOS G298T polymorphism and the effect of genotype on the measurements is discussed. Overall, there was a non-significant trend towards increased endothelium-dependent vasodilation following both acute and chronic FVPD consumption. However, there was a significant time x treatment effect (P < 0.05) of acute FVPD consumption in individuals with the GG variant of the eNOS gene.

Plant- and marine-derived n-3 polyunsaturated fatty acids have differential effects on fasting and postprandial blood lipid concentrations and on the susceptibility of LDL to oxidative modification in moderately hyperlipidemic subjects

Background: Dietary a-linolenic acid (ALA) can be converted to long-chain n-3 polyunsaturated fatty acids (PUFAs) in humans and may reproduce some of the beneficial effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on cardiovascular disease risk factors. Objective: This study aimed to compare the effects of increased dietary intakes of ALA and EPA+DHA on a range of atherogenic risk factors. Design: This was a placebo-controlled, parallel study involving 150 moderately hyperlipidemic subjects randomly assigned to 1 of 5 interventions: 0.8 or 1.7 g EPA+DHA/d, 4.5 or 9.5 g ALA/d, or an n-6 PUFA control for 6 mo. Fatty acids were incorporated into 25 g of fat spread and 3 capsules to be consumed daily. Results: The change in fasting or postprandial lipid, glucose, or insulin concentrations or in blood pressure was not significantly different after any of the n-3 PUFA interventions compared with the n-6 PUFA control. The mean (+/-SEM) change in fasting triacylglycerols after the 1.7-g/d EPA+DHA intervention (-7.7 +/- 4.99%) was significantly (P < 0.05) different from the change after the 9.5-g/d ALA intervention (10.9 +/- 4.5%). The ex vivo susceptibility of LDL to oxidation was higher after the 1.7-g/d EPA+DHA intervention than after the control and ALA interventions (P < 0.05). There was no significant change in plasma a-tocopherol concentrations or in whole plasma antioxidant status in any of the groups. Conclusion: At estimated biologically equivalent intakes, dietary ALA and EPA+DHA have different physiologic effects.

A randomised trial to investigate the effects of acute consumption of a blackcurrant juice drink on markers of vascular reactivity and bioavailability of anthocyanins in human subjects

Objective: To study the bioavailability of anthocyanins and the effects of a 20% blackcurrant juice drink on vascular reactivity, plasma antioxidant status and other CVD risk markers. Subjects/Methods: The study was a randomised, cross over, double blind, placebo controlled acute meal study. Twenty healthy volunteers (11 females 9 males) were recruited, and all subjects completed the study. Fasted volunteers consumed a 20% blackcurrant juice drink (250 ml) or a control drink following a low-flavonoid diet for the previous 72 hours. Vascular reactivity was assessed at baseline and 120 mins after juice consumption by Laser Doppler Imaging (LDI). Plasma and urine samples were collected periodically over an 8 hour period for analysis, with a final urine sample collected at 24h. The cross over was performed after a 4-week washout. Results: There were no significant effects of the 20% blackcurrant juice drink on acute measures of vascular reactivity, biomarkers of endothelial function or lipid risk factors. Consumption of the test juice caused increases in plasma vitamin C (P=0.006), and urinary anthocyanins (P<0.001). Delphinidin-3-rutinoside and cyanidin-3-rutinoside were the main anthocyanins excreted in urine with delphinidin-3-glucoside also detected. The yield of anthocyanins in urine was 0.021 ± 0.003% of the dietary intake of delphinidin glycosides and 0.009 ± 0.002 % of the dietary intake of cyanidin glycosides. Conclusions: The juice consumption did not have a significant effect on vascular reactivity. Anthocyanins were present at low concentrations in the urine, and microbial metabolites of flavonoids were detected in plasma after juice consumption.