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Biomedical subjects

G G Duthie

Publications and source records attributed to G G Duthie.

At least 19 recordsLinked to original sources

The effects of cranberry juice consumption on antioxidant status and biomarkers relating to heart disease and cancer in healthy human volunteers.

BACKGROUND: Consumption of fruit and vegetables is associated with a decreased risk of heart disease and cancer. This has been ascribed in part to antioxidants in these foods inactivating reactive oxygen species involved in initiation or progression of these diseases. Non-nutritive anthocyanins are present in significant amounts in the human diet. However, it is unclear whether they have health benefits in humans. AIM: To determine whether daily consumption of anthocyanin-rich cranberry juice could alter plasma antioxidant activity and biomarkers of oxidative stress. METHODS: 20 healthy female volunteers aged 18-40 y were recruited. Subjects consumed 750 ml/day of either cranberry juice or a placebo drink for 2 weeks. Fasted blood and urine samples were obtained over 4 weeks. The total phenol, anthocyanin and catechin content of the supplements and plasma were measured. Anthocyanin glycosides were identified by tandem mass spectrometry (MS-MS). Vitamin C, homocysteine (tHcy) and reduced glutathione (GSH) were measured by HPLC. Total antioxidant ability was determined using electron spin resonance (ESR) spectrometry and by the FRAP assay. Plasma total cholesterol, high density lipoprotein (HDL), and low density lipoprotein (LDL) cholesterol and triglycerides (TG) were measured. Glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD) activities were measured in erythrocytes. Urine was collected for analysis of malondialdehyde (MDA) by HPLC and 8-oxo-deoxyguanosine (8-oxo-dG) by ELISA. Endogenous and induced DNA damage were measured by single cell gel electrophoresis (SCGE) in lymphocytes. RESULTS: Vitamin C, total phenol, anthocyanin and catechin concentrations and FRAP and ESR values were significantly higher in the cranberry juice compared with the placebo. Cyanidin and peonidin glycosides comprised the major anthocyanin metabolites [peonidin galactoside (29.2%) > cyanidin arabinoside (26.1%) > cyanidin galactoside (21.7%) > peonidin arabinoside (17.5%) > peonidin glucoside (4.1%) > cyanidin glucoside (1.4 %)]. Plasma vitamin C increased significantly (P<0.01) in volunteers consuming cranberry juice. No anthocyanins (plasma) or catechins (plasma or urine) were detectable and plasma total phenols, tHcy,TC,TG,HDL and LDL were unchanged. The antioxidant potential of the plasma, GSH-Px, CAT and SOD activities, and MDA were similar for both groups. Supplementation with cranberry juice did not affect 8-oxo-deoxyguanosine in urine or endogenous or H(2)O(2)-induced DNA damage in lymphocytes. CONCLUSIONS: Cranberry juice consumption did not alter blood or cellular antioxidant status or several biomarkers of lipid status pertinent to heart disease. Similarly, cranberry juice had no effect on basal or induced oxidative DNA damage. These results show the importance of distinguishing between the in vitro and in vivo antioxidant activities of dietary anthocyanins in relation to human health.

Adolescent↗

Oxidative stress in colon tissue induced by vitamin E depletion.

Inflammatory disorders of the bowel and colon cancer are associated with elevated indices of oxidative stress. Analogous elevations in markers of oxidative stress and loss of cell-membrane integrity are also observed in the colons of rats deficient in vitamin E (D-alpha-tocopherol), the major lipid-soluble antioxidant in biological systems. The causal relationship between colon pathologies associated with oxidative stress and dietary deficiency in antioxidant vitamins such as vitamin E is still uncertain. Investigation of potential mechanisms by which lack of dietary vitamin E may lead to clinically relevant pathological changes in colon tissue was conducted using gene expression profiling strategies on vitamin E-sufficient and -deficient rats. Morphological changes and increased indices of lipid peroxidation were linked to vitamin E deficiency. These changes in colon tissue are potentially important in disease pathogenesis of the colon linked with oxidative stress or other direct consequences of inadequate levels of vitamin E.

Animals↗

Anthocyanin-rich extract decreases indices of lipid peroxidation and DNA damage in vitamin E-depleted rats.

Anthocyanins are secondary plant metabolites responsible for the blue, purple, and red color of many plant tissues. The phenolic structure of anthocyanins conveys marked antioxidant activity in model systems via donation of electrons or hydrogen atoms from hydroxyl moieties to free radicals. Dietary intakes of anthocyanins may exceed 200 mg/day, however, little is known about their antioxidant potency in vivo. Consequently, the aim of this study was to establish whether anthocyanins could act as putative antioxidant micronutrients. Rats were maintained on vitamin E-deficient diets for 12 weeks in order to enhance susceptibility to oxidative damage and then repleted with rations containing a highly purified anthocyanin-rich extract at a concentration of 1 g/kg diet. The extract consisted of the 3-glucopyranoside forms of delphinidin, cyanidin, petunidin, peonidin, and malvidin. Consumption of the anthocyanin-repleted diet significantly improved (p <.01) plasma antioxidant capacity and decreased (p <.001) the vitamin E deficiency-enhanced hydroperoxides and 8-Oxo-deoxyguanosine concentrations in liver. These compounds are indices of lipid peroxidation and DNA damage, respectively. Dietary consumption of anthocyanin-rich foods may contribute to overall antioxidant status, particularly in areas of habitually low vitamin E intake.

8-Hydroxy-2'-Deoxyguanosine↗

Extraction of phenolics and changes in antioxidant activity of red wines during vinification.

The moderate consumption of alcoholic beverages has been associated with protection against the development of coronary heart disease. Although alcohol itself can help prevent coronary heart disease through a number of mechanisms, red wine appears to offer protection above and beyond that attributable to alcohol alone. Red wine is a complex fluid containing grape, yeast, and wood-derived phenolic compounds, the majority of which have been recognized as potent antioxidants. The aim of this study was to investigate the major phenolic contributors to the antioxidant activity of wine. To this end, four wines were followed during the first 7-9 days of vinification. Individual phenolic compounds were quantified by HPLC, and antioxidant activity was determined by electron spin resonance spectroscopy. The extraction of the phenolics was found to be influenced by vinification procedure, grape quality, and grape variety. Although fermenting wines reached a total phenolic content comparable to that of a bottled wine after 9 days of vinification, the antioxidant activity was significantly lower than that of a finished wine. This suggests that the larger polyphenolic complexes and condensation products that appear during aging make a sizable contribution to the overall antioxidant activity of red wines.

Anthocyanins↗

High-performance liquid chromatographic determination of quercetin and isorhamnetin in rat tissues using beta-glucuronidase and acid hydrolysis.

Quercetin is a plant polyphenol which is present in the diet as an aglycone and as sugar conjugates. Despite potent vasodilatory and antioxidant effects in vitro, destruction by intestinal organisms has been assumed to limit its nutritional relevance in the rat. However, we have refined extraction techniques using beta-glucuronidase followed by acid hydrolysis. Following this with HPLC methodology with post-column derivatisation, we have detected significant concentrations of quercetin and its metabolite, isorhamnetin, in tissues of rats maintained on quercetin-rich diets. Percentage recoveries are greater than 95% and intra-batch variation does not exceed 7% suggesting that the method may be useful in further studies of the biological role of this flavonoid.

Acids↗

Relationship among antioxidant activity, vasodilation capacity, and phenolic content of red wines.

The relationship among antioxidant activity, based on the electron-spin resonance determination of the reduction of Fremy's radical, vasodilation activity, and phenolic content was investigated in 16 red wines. The wines were selected to provide a range of origins, grape varieties, and vinification methods. Sensitive and selective HPLC methods were used for the analysis of the major phenolics in red wine: free and conjugated myricetin, quercetin, kaempferol, and isorhamnetin; (+)-catechin, (-)-epicatechin, gallic acid, p-coumaric acid, caffeic acid, caftaric acid, trans-resveratrol, cis-resveratrol, and trans-resveratrol glucoside. Total anthocyanins were measured using a colorimetric assay. The total phenolic content of the wines was determined according to the Folin-Ciocalteu colorimetric assay and also by the cumulative measurements obtained by HPLC. The 16 wines exhibited a wide range in the values of all parameters investigated. However, the total phenol contents, measured both by HPLC and colorimetrically, correlated very strongly with the antioxidant activity and vasodilation activity. In addition, the antioxidant activity was associated with gallic acid, total resveratrol, and total catechin. In contrast, only the total anthocyanins were correlated with vasodilation activity. The results demonstrate that the different phenolic profiles of wines can produce varying antioxidant and vasodilatant activities, which opens up the possibility that some red wines may provide enhanced health benefits for the consumer.

Antioxidants↗

Effects of blueberry and cranberry juice consumption on the plasma antioxidant capacity of healthy female volunteers.

OBJECTIVE: To assess whether consumption of 500 ml of blueberry juice or cranberry juice by healthy female subjects increased plasma phenolic content and antioxidant capacity. DESIGN: Latin square arrangement to eliminate ordering effects. After an overnight fast, nine volunteers consumed 500 ml of blueberry juice, cranberry juice or a sucrose solution (control); each volunteer participated on three occasions one week apart, consuming one of the beverages each time. Blood samples were obtained by venipuncture at intervals up to four hours after consumption of the juices. Urine samples were also obtained four hours after consuming the juice. RESULTS: Consumption of cranberry juice resulted in a significant increase in the ability of plasma to reduce potassium nitrosodisulphonate and Fe(III)-2,4, 6-Tri(2-pyridyl)-s-triazine, these measures of antioxidant capacity attaining a maximum after 60-120 min. This corresponded to a 30% increase in vitamin C and a small but significant increase in total phenols in plasma. Consumption of blueberry juice had no such effects. CONCLUSION: The increase in plasma antioxidant capacity following consumption of cranberry juice could mainly be accounted for by an increase in vitamin C rather than phenolics. This also accounted for the lack of an effect of the phenolic-rich but vitamin C-low blueberry juice. SPONSORSHIP: Funded by the Scottish Executive Rural Affairs Department and the Danish Government.

Adult↗

Effects of organic and inorganic selenium supplementation on selenoenzyme activity in blood lymphocytes, granulocytes, platelets and erythrocytes.

The blood selenium (Se) concentration in the U.K. population has declined by approx. 50% between 1974 and 1991, reflecting a large decrease in dietary Se supply, with intakes only half the reference nutrient intake of 1 microg/kg body weight. Tissue levels of Se are readily influenced by dietary intake. Therefore selenoprotein activity may be sub-optimal due to low Se status, and thus compromise normal cell function. To examine the effects of changing Se intake on selenoproteins, we have determined the relative effectiveness of organic selenomethionine and inorganic sodium selenite (50 microg of Se daily for 28 days) in modulating glutathione peroxidase activities in blood cells from 45 healthy men and women, from a U.K. population. Transient and acute changes in lymphocyte, granulocyte and platelet phospholipid-hydroperoxide glutathione peroxidase (GPx4) activity occurred by day 7 or 14 of sodium selenite treatment and by day 7 in lymphocytes from selenomethionine-treated subjects compared with controls taking a placebo. In contrast, GPx4 activity in granulocytes and platelets in the selenomethionine group increased gradually over the 28 days. Cytosolic glutathione peroxidase (GPx1) activity in these blood cells from both treatment groups increased gradually over the 28 days. For each cellular selenoenzyme activity a significant inter-individual difference (P<0.001) in the extent of the response to Se supplementation was observed, but this was not related to blood Se concentrations either before or after treatments. Significant inverse correlations were evident between baseline enzyme activities and percentage change in activity after 28 days of supplementation [e.g. lymphocyte GPx4, r=-0.695 (P<0.001)], indicating that pre-treatment activity may be sub-optimal as a result of poor Se status. The different and contrasting effects that Se supplementation had on blood selenoenzyme activities may be indicative of a difference in metabolic need for Se regulated at the level of Se-dependent cell function.

Adult↗

Determination of activity of antioxidants in human subjects.

Evidence from biochemical and animal models suggests that nutritional antioxidants should inhibit the development of diseases such as CHD and certain cancers. This evidence is not clearly corroborated by intervention studies in human subjects, due, in part, to inadequacies in current analytical methodologies. Although in vitro assays can give useful information on the attributes required by a compound to act as an antioxidant, results may have little nutritional relevance due to limited bioavailability. The determination of antioxidants in blood is often used as a measure of antioxidant status in vivo, but may not necessarily reflect concentrations in target tissues where oxidative stress is greatest. In addition, the accumulation of antioxidants in selective tissues may not be apparent from plasma measurements. Participation in quality-control schemes for antioxidant determination by HPLC allows inter-laboratory comparison of results. Moderation of indices of oxidative damage to lipids, proteins and DNA can provide information on the effectiveness of compounds as nutritional antioxidants. However, most current methods of assessing oxidative stress are subject to confounding factors of non-oxidative origin. Assays for total antioxidant capacity in plasma differ in their type of oxidation source, target and measurement used to detect the oxidized product. They give different results, should never be used in isolation, and results should be interpreted with caution. Until more is known about the activity and metabolic fate of antioxidants, caution should be exercised in the consumption of large amounts of commercially-available antioxidant preparations.

Antioxidants↗

Assessment of the antioxidant potential of scotch whiskeys by electron spin resonance spectroscopy: relationship to hydroxyl-containing aromatic components.

Electron spin resonance (ESR) spectroscopy has been used to assess the antioxidant capacity of eight Scotch whiskeys by measuring the extent by which the original spirits, or pyridine solutions of their residues, reduced Fremy's radical or galvinoxyl radical. All whiskeys displayed antioxidant activity greater than that of a 0.2 mM solution of Trolox in the Fremy's assay and of a 0.1 mM solution of quercetin in the galvinoxyl assay. The relative antioxidant capacities determined according to the two assays were highly correlated and strongly related to the total phenol content as determined by using the Folin-Ciocalteu method. Activity was a consequence of maturation in oak casks with the "newmake" spirit showing no effect. Of 10 aromatic constituents analyzed, activity was most strongly correlated with ellagic acid and gallic acid in both assays. The reductive capacities of four major phenolics were determined, which, in summation, accounted for 31-53% of the total antioxidant activity of the whiskeys. There was no evidence for synergistic interaction between the phenols investigated.

Alcoholic Beverages↗

Dietary intakes of polyunsaturated fatty acids and indices of oxidative stress in human volunteers.

OBJECTIVE: To assess whether nutritionally-relevant changes in polyunsaturated fatty acid (PUFA) intake alter indices of oxidative stress in human volunteers DESIGN: A split plot/change over dietary study where half the volunteers consumed a diet containing 5% PUFA (low PUFA) as food energy for 4 weeks and after a 6 week washout period consumed a 15% PUFA (high PUFA) diet for another 4 weeks. The second group of volunteers completed this protocol in reverse. Total fat, carbohydrate, protein and vitamin E contents of the diets were constant. SUBJECTS: 10 healthy, non-smoking, male volunteers aged 32.6 +/- 1.7 y RESULTS: There was a significant increase in whole blood oxidised glutathione (P < 0.05), an index of oxidative stress, after consumption of the high PUFA diet. Moreover, urinary thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation, significantly increased (P = 0.038) following consumption of the high PUFA diet and decreased (P = 0.031) after consuming the low PUFA diet. However, there was no change in non specific plasma indices of lipid peroxidation, conjugated dienes and TBARS, nor in red cell antioxidant enzymes glutathione peroxidase, glutathione reductase, and catalase. However, superoxide dismutase significantly decreased (13%, P=0.018) after consumption of the low PUFA diet. Total cholesterol increased by 13% (P=0.014) after consumption of the low PUFA diet. CONCLUSIONS: This study indicates that although increasing dietary levels of PUFA may favourably alter cholesterol profiles, the same dietary changes may adversely affect some indices of lipid peroxidation. Care should be taken when providing dietary advice on PUFA intake and an adequate intake of antioxidants to match any increased PUFA may be important for preventing oxidative stress.

Adult↗

Vitamin E supplementation increases the stability and the in vivo antioxidant capacity of refined olive oil.

Two experiments were carried out to investigate if the supplementation with vitamin E affects refined olive oil response to oxidation regarding the stability of the oil and the protection in vivo against lipid peroxidation in rats after its intake in comparison with other edible oils. In experiment 1, samples of virgin olive oil, refined olive oil, refined olive oil supplemented by us with 200 mg/kg vitamin E, and sunflower oil were collected before and after a 60 min frying process. After frying, refined olive oil supplemented with vitamin E compared with the non-supplemented refined olive oil had a higher concentration of alpha-tocopherol (240.34+/-6.07 mg/kg vs. 131.94+/-8.14 mg/kg), more resistance against oxidation (19.01+/-1.88% vs. 10.6+/-2.08%) and less polar components (4.2+/-0.06% vs. 5.45+/-0.22%). In experiment 2, 24 male Wistar rats, divided into 4 groups, were fed on diets based on the same unfried oils (8% w/w) as in experiment 1, for 4 weeks. Two days prior to the end of the experiment, the rats were intraperitoneally administered with adriamycin (10 mg/kg/ day) to provoke an oxidative stress. The rats fed on refined olive oil plus vitamin E compared to the rats fed on non-supplemented refined olive oil had lower hydroperoxides concentrations (26.8+/-2.6 nmol/mg vs. 35.6+/-2.49 nmol/mg) higher coenzyme Q levels (128.1+/-11.97 pmol/mg vs. 81.25+/-9.25 pmol/mg) and higher alpha-tocopherol values (1.23+/-0.04 mmol/mg vs. 0.93+/-0.06 mmol/mg) in microsomes of liver. In conclusion, the supplementation of refined olive oil with 200 mg/kg of vitamin E increases the stability of this oil under pro-oxidant conditions, and its intake decreases the oxidative damage generated by adriamycin in rats.

Animals↗

The effect of increased intakes of polyunsaturated fatty acids and vitamin E on DNA damage in human lymphocytes.

The effect of increasing dietary intakes of polyunsaturated fatty acids (PUFAs) and vitamin E on indices of oxidative DNA damage was investigated. Twenty-one healthy male, nonsmokers aged 28.9 +/- 1.3 years participated in a free-living, split plot/change over trial in which half the volunteers consumed diets containing 5% PUFA as food energy for 4 wk and, after a 10 wk washout period, consumed a 15% PUFA diet for another 4 wk. The other volunteers followed an identical protocol, except that they consumed the 15% PUFA diet first. The diets were provided to volunteers either with or without an additional 80 mg dalpha-tocopherol acetate/day; otherwise total fat, carbohydrates, protein, and basal vitamin E contents remained unchanged. DNA damage induced by 200 microM H(2)O(2) in lymphocytes from volunteers as well as endogenous DNA damage in the form of oxidized pyrimidines, measured by alkaline single-cell gel electrophoresis (the comet assay), significantly decreased after consumption of the 5% PUFA diet (P<0.001 and P=0.01, respectively), but significantly increased after consumption of the 15% PUFA diet when alpha-tocopherol levels were in the range of 5-7 mg/day (P=0. 008 and P=0.03, respectively). These changes were abolished by an additional 80 mg dalpha-tocopherol/day. This study indicates that increasing dietary levels of PUFA to 15% may adversely affect some indices of DNA stability. However, increasing the dietary intake of vitamin E by 80 mg/day ameliorates the damaging effects of PUFA. -Jenkinson, A. McE., Collins, A. R., Duthie, S. J., Wahle, K. W. J., Duthie, G. G. The effect of increased intakes of polyunsaturated fatty acids and vitamin E on DNA damage in human lymphocytes.

Adult↗

Effects of antioxidants on vascular health.

Substantial in vitro and animal model evidence implicates the free radical-mediated oxidation of low density lipoprotein and its subsequent preferential uptake by macrophages in the arterial intima as an important factor in the development of vascular disease. In addition, antioxidants which prevent the oxidation of LDL in vitro also reduce the severity of vascular disease in animal models. Although some epidemiological studies also suggest that inadequate antioxidant status is related to the development of vascular disease, particularly cardiovascular disease, results from intervention trials have been contradictory. Whereas vitamin E may have a role in reducing the incidence of vascular disease, evidence is less strong for vitamin C, flavonoids and beta-carotene. Additionally, supplementation with some antioxidants such as beta-carotene may increase the incidence of cancer in high risk groups. Although increasing antioxidant intake is generally beneficial for health, this should perhaps be achieved by an increased dietary intake of antioxidant-rich foods rather than by use of supplements.

Animals↗

Antioxidant efficacy of phytoestrogens in chemical and biological model systems.

Phytoestrogens (PEs) are diphenolic compounds from plants which can bind to estrogen receptors and have estrogen and antiestrogen effects in man and animals. Like other plant phenolics, PEs may have antioxidant properties through hydrogen/electron donation via hydroxyl groups. They might therefore act as free radical scavengers and inhibit development of coronary heart disease and cancers. The hydrogen-donating ability of a range of phytoestrogens was assessed using electron spin resonance spectroscopy, the ferric-reducing ability of plasma assay, and the Trolox equivalent antioxidant capacity. In addition, the ability of compounds to inhibit lipid peroxidation was examined in vitamin E-deficient liver microsomes. Genistein had the highest activity of the isoflavones; however, the isoflavones were relatively poor hydrogen donors compared with the other estrogenic compounds examined. Coumestrol and equol were more effective antioxidants than genistein but had relatively limited activity in comparison with Trolox. The only estrogenic compound with significant antioxidant activity was kaempferol which is better known as a dietary antioxidant than a phytoestrogen. As the concentrations of PEs used in this study exceed the estimated serum concentrations, their relatively poor antioxidant ability in vitro may indicate little significance as antioxidants in vivo.

Animals↗

An evaluation of germinating beans as a source of vitamin C in refugee foods.

OBJECTIVE: To assess whether germinating pulses and beans are a potential source of vitamin C in rations for refugee communities with poor vitamin C status. DESIGN: High pressure liquid chromatographic assessment of vitamin C content of a range of legumes following germination in light and dark and after cooking. RESULTS: Many species of pulses produced significant quantities of vitamin C up to five days following germination in both light and dark although cooking caused a marked loss of ascorbate. CONCLUSION: Germination of approximately half of the seeds of the pulse constituents of many basic rations would be likely to generate, within a 3-5 d germination period, sufficient ascorbate to provide the 10 mg needed to protect adults against the development of scurvy.

Ascorbic Acid↗