Anthocyanins are detected in human plasma after oral administration of an elderberry extract.
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Administration, Oral↗
Biomedical subjects
R L Prior
Publications and source records attributed to R L Prior.
Long-term dietary strawberry, spinach, or vitamin E supplementation retards the onset of age-related neuronal signal-transduction and cognitive behavioral deficits.
Recent research has indicated that increased vulnerability to oxidative stress may be the major factor involved in CNS functional declines in aging and age-related neurodegenerative diseases, and that antioxidants, e.g., vitamin E, may ameliorate or prevent these declines. Present studies examined whether long-term feeding of Fischer 344 rats, beginning when the rats were 6 months of age and continuing for 8 months, with diets supplemented with a fruit or vegetable extract identified as being high in antioxidant activity, could prevent the age-related induction of receptor-mediated signal transduction deficits that might have a behavioral component. Thus, the following parameters were examined: (1) oxotremorine-enhanced striatal dopamine release (OX-K+-ERDA), (2) cerebellar beta receptor augmentation of GABA responding, (3) striatal synaptosomal 45Ca2+ clearance, (4) carbachol-stimulated GTPase activity, and (5) Morris water maze performance. The rats were given control diets or those supplemented with strawberry extracts (SE), 9.5 gm/kg dried aqueous extract (DAE), spinach (SPN 6.4 gm/kg DAE), or vitamin E (500 IU/kg). Results indicated that SPN-fed rats demonstrated the greatest retardation of age-effects on all parameters except GTPase activity, on which SE had the greatest effect, whereas SE and vitamin E showed significant but equal protection against these age-induced deficits on the other parameters. For example, OX-K+-ERDA enhancement was four times greater in the SPN group than in controls. Thus, phytochemicals present in antioxidant-rich foods such as spinach may be beneficial in retarding functional age-related CNS and cognitive behavioral deficits and, perhaps, may have some benefit in neurodegenerative disease.
Aging↗
Increases in human plasma antioxidant capacity after consumption of controlled diets high in fruit and vegetables.
BACKGROUND: The putative beneficial effects of an increased consumption of fruit and vegetables have been associated with antioxidant nutrients. However, the effect of fruit and vegetable consumption on the overall antioxidant status in humans is unclear. OBJECTIVE: The objective of this study was to investigate whether a diet rich in fruit and vegetables would affect the antioxidant capacity of human plasma. DESIGN: Thirty-six healthy nonsmokers resided in a metabolic research unit and consumed 2 sets of controlled diets. Diet A contained 10 servings of fruit and vegetables each day for 15 d. Diet B was the same as diet A, except diet B also provided 2 servings of broccoli each day on days 6-10. There was a free-living period of a minimum of 6 wk between the 2 experiments using either diet A or diet B. Fasting plasma antioxidant capacity, measured as oxygen radical absorbance capacity (ORAC), and alpha-tocopherol concentrations were determined on days 1, 6, 11, and 16. RESULTS: The fasting baseline plasma ORAC of these subjects was significantly correlated with their estimated daily intake of total antioxidants from fruit and vegetables during the previous year. Plasma ORAC of these subjects was significantly increased by both diets A and B. This increase in ORAC could not be explained by the increase in the plasma alpha-tocopherol concentration. CONCLUSION: Increased consumption of fruit and vegetables can increase the plasma antioxidant capacity in humans.
Adult↗
Serum antioxidant capacity is increased by consumption of strawberries, spinach, red wine or vitamin C in elderly women.
It is often assumed that antioxidant nutrients contribute to the protection afforded by fruits, vegetables, and red wine against diseases of aging. However, the effect of fruit, vegetable and red wine consumption on the overall antioxidant status in human is unclear. In this study we investigated the responses in serum total antioxidant capacity following comsumption of strawberries (240 g), spinach (294 g), red wine (300 ml) or vitamin C (1250 mg) in eight elderly women. Total antioxidant capacity was determined using different methods: oxygen radical absorbance capacity (ORAC) assay, Trolox equivalent antioxidant capacity (TEAC) assay and ferric reducing ability (FRAP) assay. The results showed that the total antioxidant capacity of serum determined as ORAC, TEAC and FRAP, using the area under the curve, increased significantly by 7-25% during the 4-h period following consumption of red wine, strawberries, vitamin C or spinach. The total antioxidant capacity of urine determined as ORAC increased (P < 0.05) by 9.6, 27.5, and 44.9% for strawberries, spinach, and vitamin C, respectively, during the 24-h period following these treatments. The plasma vitamin C level after the strawberry drink, and the serum urate level after the strawberry and spinach treatments, also increased significantly. However, the increased vitamin C and urate levels could not fully account for the increased total antioxidant capacity in serum following the consumption of strawberries, spinach or red wine. We conclude that the consumption of strawberries, spinach or red wine, which are rich in antioxidant phenolic compounds, can increase the serum antioxidant capacity in humans. J. Nutr. 2383-2390, 1998
Aged↗
Postprandial plasma carotenoid responses following consumption of strawberries, red wine, vitamin C or spinach by elderly women.
This study investigated the postprandial plasma responses of carotenoids for 24 h after feeding five specific breakfast beverages; four of which had low or no carotenoid content. In seven fasting healthy elderly female subjects a blood sample (baseline) was obtained, after which they were given a breakfast beverage, containing one of the following: 1) strawberries (240 g); 2) ascorbic acid (1250 mg); 3) spinach (294 g); 4) red wine (300 mL); and 5) control (breakfast beverage only). Blood samples were collected at 0.5, 1, 4, 7, 11, 15 and 24 h. Plasma carotenoids were measured using HPLC. No significant differences were found in the levels of the plasma carotenoids measured among the various treatments at baseline. In the spinach treatment, plasma lutein, zeaxanthin and beta-carotene levels at 7, 11, 15 and 24 h were significantly higher than those at baseline, as expected. All of the carotenoids measured in the control and vitamin C treatments, at subsequent sampling times were not significantly different from those at baseline. However, for most carotenoids, strawberry and red wine feeding resulted in significantly lower carotenoids values from baseline at 11 and 15 h. Subjects who received a diet with low levels of carotenoids, but whose postprandial plasma levels of carotenoids remain steady, might be explained by a mechanism that promotes secretion of carotenoids into the circulation. Assuming that plasma carotenoids are being used over time, we hypothesize that strawberries and red wine contain some substances that interfere with the secretion of carotenoids into the circulation.
Aged↗
Comparison of different analytical methods for assessing total antioxidant capacity of human serum.
Three assays were compared for the determination of total antioxidant capacity in human serum: the oxygen radical absorbance capacity (ORAC) assay, the Randox Trolox-equivalent antioxidant capacity (Randox-TEAC) assay, and the ferric reducing ability (FRAP) assay. There was a weak but significant linear correlation between serum ORAC and serum FRAP. There was no correlation either between serum ORAC and serum TEAC or between serum FRAP and serum TEAC. The effect of dilution on the serum TEAC value and the use of inhibition percentage at a fixed time, without considering the length of inhibition time in the quantitation of results, adversely affected the Randox-TEAC assay. The FRAP assay is simple and inexpensive but does not measure the SH-group-containing antioxidants. The ORAC assay has high specificity and responds to numerous antioxidants. By utilizing different extraction techniques in the ORAC assay, one can remove serum proteins and also make some gross differentiation between aqueous and lipid-soluble antioxidants. However, the ORAC assay requires approximately 60 min more than the FRAP or Randox-TEAC assay to quantitate results.
Aged↗
Responses of circulating urea cycle and branched-chain amino acids to feeding in adult and aged Fischer-344 rats.
Amino acid concentrations in plasma and blood were compared between adult (6 months) and aged (22 months) male rats in fed and food-deprived (fasted) states. Since feeding is known to elevate plasma amino acids, rats were sampled after food had been freely available to them and after food was withheld for 20 hours. Fourteen amino acids increased (8 to 74%) in blood and plasma in fed rats compared to food-deprived rats. Blood concentrations of four amino acids (cystine, aspartate, threonine, and phosphoserine) were increased in aged compared to adult rats, while tyrosine was 10% lower. The interaction between fed state and age was significant for the branched-chain amino acids (BCAA) as they increased 23% in the blood and plasma of fed compared to food-deprived adult rats; however, BCAA were not affected by feeding state in the aged rats. Plasma arginine concentration was 12% lower (p < 0.001) and citrulline was 20% higher (p < 0.005) in aged compared to adult rats, and consequently the citrulline:arginine ratio was elevated by 36% in aged rats. Our results demonstrate that, although the total arginine in whole blood is not altered or is increased with aging, less of the arginine is transported in the plasma of aged compared to adult rats. Furthermore, these results indicate altered metabolism of the urea cycle amino acids and BCAA with aging in the rat.
Aging↗
Antioxidant and prooxidant behavior of flavonoids: structure-activity relationships.
The antioxidant and prooxidant behavior of flavonoids and the related activity-structure relationships were investigated in this study using the oxygen radical absorbance capacity assay. Three different reactive species were used in the assay: 2,2'-azobis(2-amidino-propane) dihydrochloride, a peroxyl radical generator; Cu(2+)-H2O2, mainly a hydroxyl radical generator; and Cu2+, a transition metal. Flavonoids including flavones, isoflavones, and flavanones acted as antioxidants against peroxyl and hydroxyl radicals and served as prooxidants in the presence of Cu2+. Both the antioxidant and the copper-initiated prooxidant activities of a flavonoid depend upon the number of hydroxyl substitutions in its backbone structure, which has neither antioxidant nor prooxidant action. In general, the more hydroxyl substitutions, the stronger the antioxidant and prooxidant activities. The flavonoids that contain multiple hydroxyl substitutions showed antiperoxyl radical activities several times stronger than Trolox, an alpha-to copherol analogue. The single hydroxyl substitution at position 5 provides no activity, whereas the di-OH substitution at 3' and 4' is particularly important to the peroxyl radical absorbing activity of a flavonoid. The conjugation between rings A and B does not affect the antioxidant activity but is very important for the copper-initiated prooxidant action of a flavonoid. The O-methylation of the hydroxyl substitutions inactivates both the antioxidant and the prooxidant activities of the flavonoids.
Antioxidants↗
Conditions altering plasma concentrations of urea cycle and other amino acids in elderly human subjects.
OBJECTIVE: Describe plasma amino acid concentrations and total urinary amino acid excretion in subjects from an elderly female population. SUBJECTS: Fasting plasma samples, complete 24-hour urine samples, and 3-day diet records were obtained from 96 healthy postmenopausal women in one study and fasting plasma samples were obtained from an additional 44 subjects in 3 separate studies. In one study, nonfasting plasma samples were also collected. The subjects ranged in age from 49 to 80 years of age. Samples were obtained to allow the evaluation of the effects of fasting vs. nonfasting, normal vs. Alzheimers subjects, and level of protein intake effects. MEASURES OF OUTCOME: Heparinized plasma samples were deproteinized with a 5-sulfosalicylic acid solution and centrifuged at 14,900 x g. Deproteinized plasma and urine samples were analyzed for free amino acids on a Beckman System 6300 analyzer using a postcolumn reaction with ninhydrin to quantitate the amino acids. RESULTS AND CONCLUSIONS: It is concluded that: 1) From fasting plasma samples, 1 or 2 sampling days are sufficient to establish a characteristic concentration for most plasma amino acids. 2) Fasting amino acid concentrations do not reflect levels of dietary protein intake when dietary amino acid composition is similar. Shifts in fasting amino acid concentrations would be more indicative of changes in relative amounts of amino acids absorbed rather than level of dietary protein per se. 3) Totals of fasting plasma concentrations of arginine, citrulline and ornithine were relatively constant, but fluctuations occurred in the ratio of ornithine to arginine in the different populations; and 4) Patients with Alzheimers disease exhibited altered plasma ornithine and arginine concentrations relative to active or sedentary controls.
Aged↗
Antioxidant capacity in different tissues of young and old rats.
The antioxidant capacity in heart, liver, lung, and kidney was studied in young (6 months) and old (22 months) male Fischer 344 rats, using the oxygen radical absorbance capacity (ORAC) assay system with two different reactive oxygen species (ROS) generators. The results indicated that liver in old rats had significantly lower peroxyl radical absorbance capacity (ORACROO), units/g wet wt), but higher hydroxyl radical absorbance capacity (ORACOH), units/mg protein) than in young rats. The decreased liver ORACROO in the old rats was mainly due to the loss of cytosol protein, while the increased liver ORACOH in the old rats was a result of an increased resistance of cytosol proteins to the attack of ROS. This conclusion was further supported by the finding that the contribution of nonprotein fraction of liver cytosol to the ORACOH of the cytosol decreased with age. No effect of age was found on either ORACROO or ORACOH in other tissues. The antioxidant capacity for both ORACROO and ORACOH, was usually high in liver and kidney but low in lung and heart.
Aging↗
Sample pretreatment with nitrate reductase and glucose-6-phosphate dehydrogenase quantitatively reduces nitrate while avoiding interference by NADP+ when the Griess reaction is used to assay for nitrite.
An assay for the simultaneous measurement of nitrite and nitrate, products of nitric oxide metabolism, is described. Others have reported pretreating sample by using nitrate reductase (NR) and NADPH to reduce endogenous NO3- before assaying the resultant NO2- using the Griess reaction. However, we found that the NADP+ formed during pretreatment interfered with the Griess reaction when NADPH was used at concentrations necessary to drive the NR reaction. For instance, 500 microM NADP+ in 100 microM NaNO3- (without NR) causes a 90% interference with the formation of Griess reaction product. To limit interference, we modified the method by decreasing the NADPH concentration to 1 microM. NADPH was regenerated by coupling the NR reaction with that catalyzed by glucose-6-phosphate dehydrogenase (GD). Using this method, NaNO3- standard curves were linear up to 100 microM and coincided with control curves obtained using NaNO2- incubated in parallel. Addition of urine up to a strength of 20% did not interfere with the assay. Comparison with an alternative assay based on cadmium reduction resulted in the following linear regression: [Cd method] = 0.915*[NR-GD method] + 0.37, r2 = 0.997. Coupling GD to NR to recycle NADPH allows this cofactor to be used at a low concentration so that interference with the Griess reaction is negligible.
Animals↗
Dietary arginine deficiency and gut ammonium infusion alter flux of urea cycle intermediates across the portal-drained viscera of pigs.
The objective of these experiments in pigs were to test the hypotheses that 1) gut synthetic processes could adapt to additional dietary glutamate or ornithine to meet tissue needs for arginine with feeding arginine-deficient diets and 2) acute elevation of ammonium in the hepatic-portal blood leads to increased glutamine production. Arterial [117 +/- 5.3 (arginine-deficient) vs. 78 +/- 5 (arginine-adequate) mumol/L] and portal ammonium concentrations were elevated in pigs fed arginine-deficient diets. Dietary ornithine, which elevated portal-drained visceral flux of ornithine, corrected the urinary orotic aciduria, but not the hyperammonemia seen with feeding arginine-deficient diets. Concentrations or portal drained viscera fluxes of arginine, ornithine, glutamate and glutamine were not altered even though portal and arterial ammonium concentrations were increased 8- and 3.5-fold with mesenteric infusion of ammonium. It was concluded that 1) substitution of glutamate for glycine or alanine does not alter gut production of ornithine, citrulline or arginine; 2) gut citrulline production is not altered by levels of dietary arginine, ornithine or glutamate; 3) increased ammonium challenge does not lead to increased glutamine production even though peripheral ammonium levels increased over threefold; and 4) provision of arginine for tissue needs will have to be met from dietary sources, as adaptations in gut synthetic processes seem to be refractory to dietary arginine status.
Alanine↗
Automated assay of oxygen radical absorbance capacity with the COBAS FARA II.
Reactive oxygen species are of interest in biology and medicine because of evidence relating them to aging and disease processes. A relatively simple but sensitive and reliable method for quantifying the oxygen radical absorbance capacity (ORAC) of antioxidants in biological tissues has been automated for use with the COBAS FARA II centrifugal analyzer with a fluorescence-measuring attachment. In this assay, beta-phycoerythrin (beta-PE) is used as an indicator protein, 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) as a peroxyl radical generator, and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox) as a calibrator for antioxidant activity. This assay is unique because the reaction goes to completion so that both inhibition time and inhibition degree are considered in quantifying ORAC (micromoles of Trolox equivalent per liter or per gram of tissue). This method can be used not only for serum but also other tissue and food samples and is suitable for application to a range of nutritional and clinical conditions.
Animals↗
Dietary citrulline but not ornithine counteracts dietary arginine deficiency in rats by increasing splanchnic release of citrulline.
Ornithine and citrulline have different arginine-sparing capabilities when provided in an arginine-deficient diet. Rats were fed arginine-deficient diets containing ornithine or citrulline to see the effect on net fluxes of free arginine, ornithine and citrulline across the portal-drained viscera (PDV) and liver. The diets contained either 10 g arginine/kg diet (+Arg) or no arginine: the -Arg/+Ala diet contained additional alanine and the -Arg/+Orn and -Arg/+Cit diets contained ornithine and citrulline, respectively, in amounts isomolar to the amount of arginine in the control (+Arg) diet. Blood arginine concentrations were 50% lower than control values (P < 0.001) in rats fed the -Arg/+Ala or the -Arg/+Orn diet. However, addition of citrulline to the arginine-deficient diet restored blood arginine concentrations. The source of the circulating arginine in the rats fed the -Arg/+Cit diet was neither the PDV nor the liver; net splanchnic uptake of arginine was 0.3 mumol/min. Net citrulline release was substantial from the PDV (0.65 mumol/min) as well as from the splanchnic bed (0.67 mumol/min) of rats fed the -Arg/+Cit diet, such that blood citrulline concentrations were more than double (P < 0.001) those in rats fed the +Arg or -Arg/+Orn diet. Splanchnic release of citrulline in rats fed the -Arg/+Cit diet but not in rats fed the -Arg/+Orn diet supported the production of arginine in non-splanchnic organs such as, presumably, the kidney.
Alanine↗
Effects of mesenteric vein L-alanine infusion on liver metabolism of organic acids by beef heifers fed diets differing in forage: concentrate ratio.
Effects of diet forage:concentrate ratio and mesenteric vein L-alanine infusion on net VFA metabolism by portal-drained viscera (PDV) and liver were determined in four multicatheterized Hereford x Angus heifers (443 kg BW) fed in equal meals every 2 h pelleted, isonitrogenous diets containing 75% alfalfa or 75% corn:soybean meal (SBM) in a balanced single reversal of diets with 6 wk for adaptation. In addition, effects of L-alanine infusion on net metabolism of individual amino acids (AA) by PDV and liver was determined when heifers were fed 75% corn:SBM. Four measurements of blood flow (p-aminohippurate dilution) and net flux of VFA and AA (venous-arterial difference times blood flow) were obtained at 30-min intervals immediately before beginning and ending a 24-h mesenteric vein infusion of L-alanine at 75 mmol/h. Net PDV absorption of acetate (P < .02), propionate (P < .02), and total VFA (P < .02) was lower when 75% corn:SBM was fed, reflecting increased carbohydrate digestion postruminally and only partially balanced by increases in net PDV glucose absorption reported previously. In addition, net PDV absorption of n-butyrate was lower when 75% alfalfa was fed. Excluding acetate, net liver removal of VFA was 83 to 108% of their net PDV release. L-Alanine infusion did not affect net PDV or liver flux of VFA but decreased net total splanchnic (PDV plus liver) release of propionate (P < .07) and n-butyrate (P < .03) and decreased (P < .10) net PDV release and liver removal of glycine. In spite of the increase in liver L-alanine removal, the ratio of glucose release to precursor removal remained remarkably constant across the liver when L-alanine was infused, emphasizing the tight control of liver glucose release and the dynamic interplay of precursor supply and removal in the maintenance of liver carbon balance.
Alanine↗
Oral arginine supplementation does not affect lymphocyte proliferation during endotoxin-induced inflammation in rats.
Earlier studies from this laboratory were unable to confirm reported immunostimulatory effects of supplemental dietary arginine on healthy, unstressed young or aged rats. The present study was undertaken to determine effects of oral arginine supplementation on in vitro measures of immune function using a stressed rat model. The stressor used was intraperitoneal injection of bacterial lipopolysaccharide (1 mg/kg body wt). Four-month-old male Sprague-Dawley rats were placed in either a control or an arginine-supplemented (7.5 g/L arginine-HCl in drinking water) group for 7 d, after which control and supplemented rats received injections of endotoxin or phosphate-buffered saline. Rats were killed 3 d following injections. Endotoxin treatment resulted in lower food intake, less thymic cellularity and greater splenic weight. Endotoxin injections also enhanced proliferative response of rat splenocytes to pokeweed mitogen (1 mg/L) and lipopolysaccharide (25 and 100 mg/L) and enhanced response of thymocytes to concanavalin A (10 mg/L), phytohemagglutinin (25 and 100 mg/L) and pokeweed mitogen (1 mg/L). Supplemental arginine did not reduce thymic weight loss or influence mononuclear cell proliferation or interleukin-2 production in the presence or absence of endotoxin stress. These data indicate no benefit of arginine supplementation during endotoxin stress in rats.
Animals↗
Time after feeding and dietary arginine deficiency alter splanchnic and hepatic amino acid flux in rats.
The effect of an arginine-deficient diet containing 3.4% glutamate on net flux of amino acids across the portal-drained viscera and liver was studied in rats at 0, 1 or 2 h after a meal and compared with that in arginine-fed controls. Net portal-drained viscera flux for most amino acids was greater in the fed state compared with the postabsorptive state except for glycine and cystine, which did not change, and methionine, which declined. Net amino acid recovery in portal blood 2 h after feeding compared with amounts consumed was highest for alanine (17.3%); recovery of other amino acids ranged from 5.6 to 15.3%. No net portal-drained viscera recovery of consumed cystine was observed. For the branched-chain and aromatic amino acids, methionine, threonine, histidine and lysine, net hepatic uptake was nearly equal to net portal-drained viscera absorption (range 77-127% of portal-drained viscera flux). Correlation coefficients between net hepatic and portal-drained viscera fluxes for leucine, valine, isoleucine, methionine and phenylalanine were 0.84 to 0.93. Postabsorptive hepatic extraction for most amino acids was zero, but after a meal, ranged from 13.3 to 22.9% for the branched-chain and aromatic amino acids. Net hepatic production of ornithine and proline occurred in arginine-fed control rats. This value was near zero for ornithine in rats fed the arginine-deficient diet. Models of interorgan amino acid metabolism in the food-deprived and fed state are presented.
Absorption↗
Dietary arginine deficiency alters flux of glutamine and urea cycle intermediates across the portal-drained viscera and liver of rats.
The effect of an arginine-deficient diet on net flux of amino acids across the portal-drained viscera and across the liver was studied in rats. Blood was obtained after food deprivation and 1 and 2 h after a meal of a 1.0% arginine control diet or an arginine-deficient diet containing 3.4% glutamate. The arginine-deficient diet decreased net portal-drained viscera flux of arginine and increased net portal-drained viscera flux of ornithine and proline. However, net portal-drained viscera flux of citrulline (0.35 +/- 0.05 mumol/min) was not influenced by diet; of this rate, 46% (0.16 mumol/min) bypassed the liver and was available for extrahepatic arginine synthesis. However, rats continued to exhibit signs of arginine deficiency such as decreased blood arginine concentrations (by 28%) and increased orotic acid excretion (90-fold). Arterial blood glutamine concentration was 25% higher in rats fed the arginine-deficient diet. In the fed state, net hepatic flux of glutamine was elevated from 0.15 (control) to 1.39 mumol/min, indicating that the liver was a major source of the increased blood glutamine concentrations. Increased production of hepatic glutamine and orotic acid may help rats compensate for dietary arginine deficiency, whereas splanchnic output of citrulline was not increased with dietary arginine deficiency even with a substantial dietary supply of glutamate.
Amino Acids↗