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Sample records for conjugated docosahexaenoic acid

  1. Docosahexaenoic Acid Conjugation Enhances Distribution and Safety of siRNA upon Local Administration in Mouse Brain

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    Mehran Nikan

    2016-01-01

    Full Text Available The use of siRNA-based therapies for the treatment of neurodegenerative disease requires efficient, nontoxic distribution to the affected brain parenchyma, notably the striatum and cortex. Here, we describe the synthesis and activity of a fully chemically modified siRNA that is directly conjugated to docosahexaenoic acid (DHA, the most abundant polyunsaturated fatty acid in the mammalian brain. DHA conjugation enables enhanced siRNA retention throughout both the ipsilateral striatum and cortex following a single, intrastriatal injection (ranging from 6–60 μg. Within these tissues, DHA conjugation promotes internalization by both neurons and astrocytes. We demonstrate efficient and specific silencing of Huntingtin mRNA expression in both the ipsilateral striatum (up to 73% and cortex (up to 51% after 1 week. Moreover, following a bilateral intrastriatal injection (60 μg, we achieve up to 80% silencing of a secondary target, Cyclophilin B, at both the mRNA and protein level. Importantly, DHA-hsiRNAs do not induce neural cell death or measurable innate immune activation following administration of concentrations over 20 times above the efficacious dose. Thus, DHA conjugation is a novel strategy for improving siRNA activity in mouse brain, with potential to act as a new therapeutic platform for the treatment of neurodegenerative disorders.

  2. Docosahexaenoic acid prevents trans-10, cis-12 conjugated linoleic acid-induced non-alcoholic fatty liver disease in mice by altering expression of hepatic genes regulating fatty acid synthesis and oxidation

    Science.gov (United States)

    Background: Concomitant supplementation with docosahexaenoic acid (22:6 n-3; DHA) prevented t10, c12- conjugated linoleic acid (CLA)-induced non-alcoholic fatty liver disease (NAFLD) and insulin resistance. Effective dose of DHA and mechanisms involved are poorly understood. Methods: We examined abi...

  3. Conjugated docosahexaenoic acid suppresses KPL-1 human breast cancer cell growth in vitro and in vivo: potential mechanisms of action

    International Nuclear Information System (INIS)

    Tsujita-Kyutoku, Miki; Ogawa, Yutaka; Tsubura, Airo; Yuri, Takashi; Danbara, Naoyuki; Senzaki, Hideto; Kiyozuka, Yasuhiko; Uehara, Norihisa; Takada, Hideho; Hada, Takahiko; Miyazawa, Teruo

    2004-01-01

    The present study was conducted to examine the effect of conjugated docosahexaenoic acid (CDHA) on cell growth, cell cycle progression, mode of cell death, and expression of cell cycle regulatory and/or apoptosis-related proteins in KPL-1 human breast cancer cell line. This effect of CDHA was compared with that of docosahexaenoic acid (DHA). KPL-1 cell growth was assessed by colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay; cell cycle progression and mode of cell death were examined by flow cytometry; and levels of expression of p53, p21 Cip1/Waf1 , cyclin D 1 , Bax, and Bcl-2 proteins were examined by Western blotting analysis. In vivo tumor growth was examined by injecting KPL-1 cells subcutaneously into the area of the right thoracic mammary fat pad of female athymic mice fed a CDHA diet. CDHA inhibited KPL-1 cells more effectively than did DHA (50% inhibitory concentration for 72 hours: 97 μmol/l and 270 μmol/l, respectively). With both CDHA and DHA growth inhibition was due to apoptosis, as indicated by the appearance of a sub-G 1 fraction. The apoptosis cascade involved downregulation of Bcl-2 protein; Bax expression was unchanged. Cell cycle progression was due to G 0 /G 1 arrest, which involved increased expression of p53 and p21 Cip1/Waf1 , and decreased expression of cyclin D 1 . CDHA modulated cell cycle regulatory proteins and apoptosis-related proteins in a manner similar to that of parent DHA. In the athymic mouse system 1.0% dietary CDHA, but not 0.2%, significantly suppressed growth of KPL-1 tumor cells; CDHA tended to decrease regional lymph node metastasis in a dose dependent manner. CDHA inhibited growth of KPL-1 human breast cancer cells in vitro more effectively than did DHA. The mechanisms of action involved modulation of apoptosis cascade and cell cycle progression. Dietary CDHA at 1.0% suppressed KPL-1 cell growth in the athymic mouse system

  4. Unesterified docosahexaenoic acid is protective in neuroinflammation

    Science.gov (United States)

    Orr, Sarah K; Palumbo, Sara; Bosetti, Francesca; Mount, Howard T; Kang, Jing X; E, Carol; Greenwood; Ma, David WL; Serhan, Charles N; Bazinet, Richard P

    2014-01-01

    Docosahexaenoic acid (22:6n-3) is the major brain n-3 polyunsaturated fatty acid and it is possible that docosahexaenoic acid is anti-inflammatory in the brain as it is known to be in other tissues. Using a combination of models including the fat-1 transgenic mouse, chronic dietary n-3 PUFA modulation in transgenic and wildtype mice, and acute direct brain infusion, we demonstrated that unesterified docosahexaenoic acid attenuates neuroinflammation initiated by intracerebroventricular lipopolysaccharide. Hippocampal neuroinflammation was assessed by gene expression and immunohistochemistry. Further, docosahexaenoic acid protected against lipopolysaccharide-induced neuronal loss. Acute intracerebroventricular infusion of unesterified docosahexaenoic acid or its 12/15-lipoxygenase product and precursor to protectins and resolvins, 17S-hydroperoxy-docosahexaenoic acid, mimics anti-neuroinflammatory aspects of chronically increased unesterified docosahexaenoic acid. LCMS/MS revealed that neuroprotectin D1 and several other docosahexaenoic acid-derived specialized pro-resolving mediators are present in the hippocampus. Acute icv infusion of 17S-hydroperoxydocosahexaenoic acid increases hippocampal neuroprotectin D1 levels concomitant to attenuating neuroinflammation. These results show that unesterified docosahexaenoic acid is protective in a lipopolysaccharide-initiated mouse model of acute neuroinflammation, at least in part, via its conversion to specialized pro-resolving mediators; these docosahexaenoic acid stores may provide novel targets for the prevention and treatment(s) of neurological disorders with a neuroinflammatory component. PMID:23919613

  5. Oxidative stability of Liposomes composed of docosahexaenoic acid-containing phospholipids

    DEFF Research Database (Denmark)

    Vikbjerg, Anders Falk; Andresen, Thomas Lars; Jørgensen, Kent

    2007-01-01

    Oxidative stability of liposomes made of (Docosahexaenoic acid) DHA-containing phosphatidylcholine (PC) was examined during preparation and storage. After preparation of the liposomes, the concentration of primary (conjugated dienes) and secondary oxidation products (Thiobarbituric acid...

  6. Effects of Docosahexaenoic Acid on Neurotransmission

    OpenAIRE

    Tanaka, Kazuhiro; Farooqui, Akhlaq A.; Siddiqi, Nikhat J.; Alhomida, Abdullah S.; Ong, Wei-Yi

    2012-01-01

    Docosahexaenoic acid (DHA) is the major polyunsaturated fatty acid (PUFA) in the brain and a structural component of neuronal membranes. Changes in DHA content of neuronal membranes lead to functional changes in the activity of receptors and other proteins which might be associated with synaptic function. Accumulating evidence suggests the beneficial effects of dietary DHA supplementation on neurotransmission. This article reviews the beneficial effects of DHA on the brain; uptake, incorporat...

  7. Docosahexaenoic Acid and Cognition throughout the Lifespan

    Directory of Open Access Journals (Sweden)

    Michael J. Weiser

    2016-02-01

    Full Text Available Docosahexaenoic acid (DHA is the predominant omega-3 (n-3 polyunsaturated fatty acid (PUFA found in the brain and can affect neurological function by modulating signal transduction pathways, neurotransmission, neurogenesis, myelination, membrane receptor function, synaptic plasticity, neuroinflammation, membrane integrity and membrane organization. DHA is rapidly accumulated in the brain during gestation and early infancy, and the availability of DHA via transfer from maternal stores impacts the degree of DHA incorporation into neural tissues. The consumption of DHA leads to many positive physiological and behavioral effects, including those on cognition. Advanced cognitive function is uniquely human, and the optimal development and aging of cognitive abilities has profound impacts on quality of life, productivity, and advancement of society in general. However, the modern diet typically lacks appreciable amounts of DHA. Therefore, in modern populations, maintaining optimal levels of DHA in the brain throughout the lifespan likely requires obtaining preformed DHA via dietary or supplemental sources. In this review, we examine the role of DHA in optimal cognition during development, adulthood, and aging with a focus on human evidence and putative mechanisms of action.

  8. Brain docosahexaenoic acid uptake and metabolism.

    Science.gov (United States)

    Lacombe, R J Scott; Chouinard-Watkins, Raphaël; Bazinet, Richard P

    2018-02-08

    Docosahexaenoic acid (DHA) is the most abundant n-3 polyunsaturated fatty acid in the brain where it serves to regulate several important processes and, in addition, serves as a precursor to bioactive mediators. Given that the capacity of the brain to synthesize DHA locally is appreciably low, the uptake of DHA from circulating lipid pools is essential to maintaining homeostatic levels. Although, several plasma pools have been proposed to supply the brain with DHA, recent evidence suggests non-esterified-DHA and lysophosphatidylcholine-DHA are the primary sources. The uptake of DHA into the brain appears to be regulated by a number of complementary pathways associated with the activation and metabolism of DHA, and may provide mechanisms for enrichment of DHA within the brain. Following entry into the brain, DHA is esterified into and recycled amongst membrane phospholipids contributing the distribution of DHA in brain phospholipids. During neurotransmission and following brain injury, DHA is released from membrane phospholipids and converted to bioactive mediators which regulate signaling pathways important to synaptogenesis, cell survival, and neuroinflammation, and may be relevant to treating neurological diseases. In the present review, we provide a comprehensive overview of brain DHA metabolism, encompassing many of the pathways and key enzymatic regulators governing brain DHA uptake and metabolism. In addition, we focus on the release of non-esterified DHA and subsequent production of bioactive mediators and the evidence of their proposed activity within the brain. We also provide a brief review of the evidence from post-mortem brain analyses investigating DHA levels in the context of neurological disease and mood disorder, highlighting the current disparities within the field. Copyright © 2017. Published by Elsevier Ltd.

  9. Expanding Awareness of Docosahexaenoic Acid during Pregnancy

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    Barbara J. Meyer

    2013-04-01

    Full Text Available Pregnant women do not currently meet the consensus recommendation for docosahexaenoic acid (DHA (≥200 mg/day. Pregnant women in Australia are not receiving information on the importance of DHA during pregnancy. DHA pregnancy education materials were developed using current scientific literature, and tested for readability and design aesthetics. The study aimed to evaluate their usefulness, the desire for pregnant women to receive these materials and whether a larger separate study (using a control group is warranted to evaluate the influence the materials may have on increasing DHA consumption in pregnant women in Australia. Pregnant women (N = 118 were recruited at antenatal clinics at two NSW hospitals. Participants completed a 16-item questionnaire and DHA educational materials (pamphlet and shopping card were provided. Participants were contacted via phone two weeks later and completed the second questionnaire (25-item, N = 74. Statistics were conducted in SPSS and qualitative data were analysed to identify common themes. Ninety three percent of women found the materials useful, with the main reason being it expanded their knowledge of DHA food sources. Only 34% of women had received prior information on DHA, yet 68% said they would like to receive information. Due to the small sample size and lack of a control group, this small study cannot provide a cause and effect relationship between the materials and nutrition related behaviours or knowledge, however the results indicate a potential positive influence towards increased fish consumption and awareness of DHA containing foods. This suggests a larger study, with a control group is warranted to identify the impact such materials could have on Australian pregnant women.

  10. Docosahexaenoic acid production by the marine algae Crypthecodinium cohnii

    NARCIS (Netherlands)

    De Swaaf, M.E.

    2003-01-01

    This thesis focuses on the production of docosahexaenoic acid (DHA; 22:6), an w-3 polyunsaturated fatty acid with applications in foods and pharmaceuticals, by Crypthecodinium cohnii. This chloroplastless heterotrophic marine microalga has been studied since the end of the nineteenth century and has

  11. Fish oil supplementation improves docosahexaenoic acid status of malnourished infants

    NARCIS (Netherlands)

    Smit, EN; Oelen, EA; Seerat, E; Boersma, ER; Muskiet, FAJ

    Aim-To investigate whether the low docosahexaenoic acid (DHA) status of malnourished, mostly breast fed, Pakistani children can be improved by fish oil (FO) supplementation. Methods-Ten malnourished children (aged 8-30 months) received 500 mg FO daily for nine weeks. The supplement contained 62.8

  12. Effect of dietary docosahexaenoic acid on biosynthesis of docosahexaenoic acid from alpha-linolenic acid in young rats

    OpenAIRE

    DeMar, James C.; DiMartino, Carmine; Baca, Adam W.; Lefkowitz, William; Salem, Norman

    2008-01-01

    Docosahexaenoic acid (DHA), a crucial nervous system n-3 PUFA, may be obtained in the diet or synthesized in vivo from dietary α-linolenic acid (LNA). We addressed whether DHA synthesis is regulated by the availability of dietary DHA in artificially reared rat pups, during p8 to p28 development. Over 20 days, one group of rat pups was continuously fed deuterium-labeled LNA (d5-LNA) and no other n-3 PUFA (d5-LNA diet), and a second group of rat pups was fed a d5-LNA diet with un...

  13. Docosahexaenoic acid affects arachidonic acid uptake in megakaryocytes

    International Nuclear Information System (INIS)

    Schick, P.K.; Webster, P.

    1987-01-01

    Dietary omega 3 fatty acids are thought to prevent atherosclerosis, possibly by modifying platelet (PT) function and arachidonic acid (20:4) metabolism. The study was designed to determine whether omega 3 fatty acids primarily affect 20:4 metabolism in megakaryocytes (MK), bone marrow precursors of PT, rather than in circulating PT. MK and PT were isolated from guinea pigs and incubated with [ 14 C]-20:4 (0.13uM). Docosahexaenoic acid (22:6) is a major omega 3 fatty acid in marine oils. The incubation of MK with 22:6 (0.1, 1.0 uM) resulted in the decrease of incorporation of [ 14 C]-20:4 into total MK phospholipids, 16% and 41% respectively. Alpha-linolenic acid (18:3), a major omega 3 fatty acid present in American diets, had no effect on 20:4 uptake in MK. 22:6 primarily affected the uptake of [ 14 C]-20:4 into phosphatidylethanolamine (PE) and phosphatidylserine (PS) in MK. In MK, 22:6 (0.1, 1.0 uM) caused a decrease of incorporation of [ 14 C]-20:4 into PE, 21% and 55% respectively; a decrease into PS, 16% and 48% respectively; but only a decrease of 4% and 18%, respectively, into phosphatidylcholine; and a decrease of 3% and 21% into phosphatidylinositol 22:6 (3.0 uM) had no effect on the uptake of AA into PT phospholipids. The study shows that 22:6 has a selective effect on AA uptake in MK and that the acylation or transacylation of PE and PS are primarily affected. 22:6 and other marine omega 3 fatty acids appear to primarily affect megakaryocytes which may result in the production of platelets with abnormal content and compartmentalization of AA

  14. Conjugated Fatty Acid Synthesis

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    Rawat, Richa; Yu, Xiao-Hong; Sweet, Marie; Shanklin, John

    2012-01-01

    Conjugated linolenic acids (CLNs), 18:3 Δ9,11,13, lack the methylene groups found between the double bonds of linolenic acid (18:3 Δ9,12,15). CLNs are produced by conjugase enzymes that are homologs of the oleate desaturases FAD2. The goal of this study was to map the domain(s) within the Momordica charantia conjugase (FADX) responsible for CLN formation. To achieve this, a series of Momordica FADX-Arabidopsis FAD2 chimeras were expressed in the Arabidopsis fad3fae1 mutant, and the transformed seeds were analyzed for the accumulation of CLN. These experiments identified helix 2 and the first histidine box as a determinant of conjugase product partitioning into punicic acid (18:3 Δ9cis,11trans,13cis) or α-eleostearic acid (18:3 Δ9cis,11trans,13trans). This was confirmed by analysis of a FADX mutant containing six substitutions in which the sequence of helix 2 and first histidine box was converted to that of FAD2. Each of the six FAD2 substitutions was individually converted back to the FADX equivalent identifying residues 111 and 115, adjacent to the first histidine box, as key determinants of conjugase product partitioning. Additionally, expression of FADX G111V and FADX G111V/D115E resulted in an approximate doubling of eleostearic acid accumulation to 20.4% and 21.2%, respectively, compared with 9.9% upon expression of the native Momordica FADX. Like the Momordica conjugase, FADX G111V and FADX D115E produced predominantly α-eleostearic acid and little punicic acid, but the FADX G111V/D115E double mutant produced approximately equal amounts of α-eleostearic acid and its isomer, punicic acid, implicating an interactive effect of residues 111 and 115 in punicic acid formation. PMID:22451660

  15. Docosahexaenoic acid induces apoptosis in primary chronic lymphocytic leukemia cells

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    Romain Guièze

    2015-12-01

    Full Text Available Chronic lymphocytic leukemia is an indolent disorder with an increased infectious risk remaining one of the main causes of death. Development of therapies with higher safety profile is thus a challenging issue. Docosahexaenoic acid (DHA, 22:6 is an omega-3 fatty acid, a natural compound of normal cells, and has been shown to display antitumor potency in cancer. We evaluated the potential in vitro effect of DHA in primary CLL cells. DHA induces high level of in vitro apoptosis compared to oleic acid in a dose-dependent and time-dependent manner. Estimation of IC50 was only of 4.813 μM, which appears lower than those reported in solid cancers. DHA is highly active on CLL cells in vitro. This observation provides a rationale for further studies aiming to understand its mechanisms of action and its potent in vivo activity.

  16. Docosahexaenoic Acid and Neurodevelopmental Outcomes of Term Infants.

    Science.gov (United States)

    Meldrum, Suzanne; Simmer, Karen

    2016-01-01

    Docosahexaenoic acid (DHA), a long-chain polyunsaturated fatty acid, is essential for normal brain development. DHA is found predominantly in seafood, fish oil, breastmilk and supplemented formula. DHA intake in Western countries is often below recommendations. Observational studies have demonstrated an association between DHA intake in pregnancy and neurodevelopment of offspring but cannot fully adjust for confounding factors that influence child development. Randomised clinical trials of DHA supplementation during pregnancy and/or lactation, and of term infants, have not shown a consistent benefit nor harm on neurodevelopment of healthy children born at term. The evidence does not support DHA supplementation of healthy pregnant and lactating women, nor healthy infants. © 2016 S. Karger AG, Basel.

  17. Human milk arachidonic acid and docosahexaenoic acid contents increase following supplementation during pregnancy and lactation

    NARCIS (Netherlands)

    van Goor, Saskia A.; Dijick-Brouwer, D. A. Janneke; Hadders-Algra, Mijna; Doornbos, Bennard; Erwich, Jan Jaap H. M.; Schaafsma, Anne; Muskiet, Frits A. J.; Djick-Brouwer, D.A.J.

    Introduction: Docosahexaenoic acid (DHA) and arachidonic acid (AA) are important for neurodevelopment. Maternal diet influences milk DHA, whereas milk AA seems rather constant. We investigated milk AA, DHA and DHA/AA after supplementation of AA plus DHA, or DHA alone during pregnancy and lactation.

  18. Biotechnological production and applications of the omega-3 polyunsaturated fatty acid docosahexaenoic acid

    NARCIS (Netherlands)

    Sijtsma, L.; Swaaf, de M.E.

    2004-01-01

    Docosahexaenoic acid (DHA) is a polyunsaturated fatty acid composed of 22 carbon atoms and six double bonds. Because the first double bond, as counted from the methyl terminus, is at position three, DHA belongs to the so-called omega-3 group. In recent years, DHA has attracted much attention because

  19. Intrauterine, postpartum and adult relationships between arachidonic acid (AA) and docosahexaenoic acid (DHA)

    NARCIS (Netherlands)

    Kuipers, Remko S.; Luxwolda, Martine F.; Dijck-Brouwer, D. A. Janneke; Muskiet, Frits A. J.

    Erythrocyte (RBC) fatty acid compositions from populations with stable dietary habits but large variations in RBC-arachidonic (AA) and RBC-docosahexaenoic acid (DHA) provided us with insight into relationships between DHA and AA. It also enabled us to estimate the maternal RBC-DHA (mRBC-DHA) status

  20. Metabotyping of docosahexaenoic acid - treated Alzheimer's disease cell model.

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    Priti Bahety

    Full Text Available BACKGROUND: Despite the significant amount of work being carried out to investigate the therapeutic potential of docosahexaenoic acid (DHA in Alzheimer's disease (AD, the mechanism by which DHA affects amyloid-β precursor protein (AβPP-induced metabolic changes has not been studied. OBJECTIVE: To elucidate the metabolic phenotypes (metabotypes associated with DHA therapy via metabonomic profiling of an AD cell model using gas chromatography time-of-flight mass spectrometry (GC/TOFMS. METHODS: The lysate and supernatant samples of CHO-wt and CHO-AβPP695 cells treated with DHA and vehicle control were collected and prepared for GC/TOFMS metabonomics profiling. The metabolic profiles were analyzed by multivariate data analysis techniques using SIMCA-P+ software. RESULTS: Both principal component analysis and subsequent partial least squares discriminant analysis revealed distinct metabolites associated with the DHA-treated and control groups. A list of statistically significant marker metabolites that characterized the metabotypes associated with DHA treatment was further identified. Increased levels of succinic acid, citric acid, malic acid and glycine and decreased levels of zymosterol, cholestadiene and arachidonic acid correlated with DHA treatment effect. DHA levels were also found to be increased upon treatment. CONCLUSION: Our study shows that DHA plays a role in mitigating AβPP-induced impairment in energy metabolism and inflammation by acting on tricarboxylic acid cycle, cholesterol biosynthesis pathway and fatty acid metabolism. The perturbations of these metabolic pathways by DHA in CHO-wt and CHO-AβPP695 cells shed further mechanistic insights on its neuroprotective actions.

  1. Docosahexaenoic Acid Reduces Amyloid β Production via Multiple Pleiotropic Mechanisms*

    Science.gov (United States)

    Grimm, Marcus O. W.; Kuchenbecker, Johanna; Grösgen, Sven; Burg, Verena K.; Hundsdörfer, Benjamin; Rothhaar, Tatjana L.; Friess, Petra; de Wilde, Martijn C.; Broersen, Laus M.; Penke, Botond; Péter, Mária; Vígh, László; Grimm, Heike S.; Hartmann, Tobias

    2011-01-01

    Alzheimer disease is characterized by accumulation of the β-amyloid peptide (Aβ) generated by β- and γ-secretase processing of the amyloid precursor protein (APP). The intake of the polyunsaturated fatty acid docosahexaenoic acid (DHA) has been associated with decreased amyloid deposition and a reduced risk in Alzheimer disease in several epidemiological trials; however, the exact underlying molecular mechanism remains to be elucidated. Here, we systematically investigate the effect of DHA on amyloidogenic and nonamyloidogenic APP processing and the potential cross-links to cholesterol metabolism in vivo and in vitro. DHA reduces amyloidogenic processing by decreasing β- and γ-secretase activity, whereas the expression and protein levels of BACE1 and presenilin1 remain unchanged. In addition, DHA increases protein stability of α-secretase resulting in increased nonamyloidogenic processing. Besides the known effect of DHA to decrease cholesterol de novo synthesis, we found cholesterol distribution in plasma membrane to be altered. In the presence of DHA, cholesterol shifts from raft to non-raft domains, and this is accompanied by a shift in γ-secretase activity and presenilin1 protein levels. Taken together, DHA directs amyloidogenic processing of APP toward nonamyloidogenic processing, effectively reducing Aβ release. DHA has a typical pleiotropic effect; DHA-mediated Aβ reduction is not the consequence of a single major mechanism but is the result of combined multiple effects. PMID:21324907

  2. Prenatal docosahexaenoic acid supplementation and infant morbidity: randomized controlled trial.

    Science.gov (United States)

    Imhoff-Kunsch, Beth; Stein, Aryeh D; Martorell, Reynaldo; Parra-Cabrera, Socorro; Romieu, Isabelle; Ramakrishnan, Usha

    2011-09-01

    Long-chain polyunsaturated fatty acids such as docosahexaenoic acid (DHA) influence immune function and inflammation; however, the influence of maternal DHA supplementation on infant morbidity is unknown. We investigated the effects of prenatal DHA supplementation on infant morbidity. In a double-blind randomized controlled trial conducted in Mexico, pregnant women received daily supplementation with 400 mg of DHA or placebo from 18 to 22 weeks' gestation through parturition. In infants aged 1, 3, and 6 months, caregivers reported the occurrence of common illness symptoms in the preceding 15 days. Data were available at 1, 3, and 6 months for 849, 834, and 834 infants, respectively. The occurrence of specific illness symptoms did not differ between groups; however, the occurrence of a combined measure of cold symptoms was lower in the DHA group at 1 month (OR: 0.76; 95% CI: 0.58-1.00). At 1 month, the DHA group experienced 26%, 15%, and 30% shorter duration of cough, phlegm, and wheezing, respectively, but 22% longer duration of rash (all P ≤ .01). At 3 months, infants in the DHA group spent 14% less time ill (P DHA group experienced 20%, 13%, 54%, 23%, and 25% shorter duration of fever, nasal secretion, difficulty breathing, rash, and "other illness," respectively, but 74% longer duration of vomiting (all P DHA supplementation during pregnancy decreased the occurrence of colds in children at 1 month and influenced illness symptom duration at 1, 3, and 6 months.

  3. Docosahexaenoyl serotonin, an endogenously formed n-3 fatty acid-serotonin conjugate has anti-inflammatory properties by attenuating IL-23–IL-17 signaling in macrophages

    NARCIS (Netherlands)

    Poland, Mieke; Klooster, ten Jean Paul; Wang, Zheng; Pieters, Raymond; Boekschoten, Mark; Witkamp, Renger; Meijerink, Jocelijn

    2016-01-01

    Conjugates of fatty acids and amines, including endocannabinoids, are known to play important roles as endogenous signaling molecules. Among these, the ethanolamine conjugate of the n-3 poly unsaturated long chain fatty acid (PUFA) docosahexaenoic acid (22:6n-3) (DHA) was shown to possess strong

  4. Docosahexaenoyl serotonin, an endogenously formed n-3 fatty acid-serotonin conjugate has anti-inflammatory properties by attenuating IL-23-IL-17 signaling in macrophages

    NARCIS (Netherlands)

    Poland, Mieke; Ten Klooster, Jean Paul; Wang, Zheng; Pieters, Raymond; Boekschoten, Mark; Witkamp, Renger; Meijerink, Jocelijn

    2016-01-01

    Conjugates of fatty acids and amines, including endocannabinoids, are known to play important roles as endogenous signaling molecules. Among these, the ethanolamine conjugate of the n-3 poly unsaturated long chain fatty acid (PUFA) docosahexaenoic acid (22:6n-3) (DHA) was shown to possess strong

  5. Docosahexaenoyl Serotonin, an endogenously formed n-3 fatty acid-serotonin conjugate, has anti-inflammatory properties by attenuating IL23–IL17 signalling in macrophages

    NARCIS (Netherlands)

    Poland, M.C.R.; Klooster, ten Jean Paul; Wang, Zheng; Pieters, Raymond; Boekschoten, M.V.; Witkamp, R.F.; Meijerink, J.

    2016-01-01

    Conjugates of fatty acids and amines, including endocannabinoids, are known to play important roles as endogenous signalling molecules. Among these, the ethanolamine conjugate of the n-3 poly unsaturated long chain fatty acid (PUFA) docosahexaenoic acid (22:6n-3) (DHA) was shown to possess strong

  6. Docosahexaenoic acid confers enduring neuroprotection in experimental stroke.

    Science.gov (United States)

    Hong, Sung-Ha; Belayev, Ludmila; Khoutorova, Larissa; Obenaus, Andre; Bazan, Nicolas G

    2014-03-15

    Recently we demonstrated that docosahexaenoic acid (DHA) is highly neuroprotective when animals were allowed to survive during one week. This study was conducted to establish whether the neuroprotection induced by DHA persists with chronic survival. Sprague-Dawley rats underwent 2h of middle cerebral artery occlusion (MCAo) and treated with DHA or saline at 3h after MCAo. Animals received neurobehavioral examination (composite neuroscore, rota-rod, beam walking and Y maze tests) followed by ex vivo magnetic resonance imaging and histopathology at 3 weeks. DHA improved composite neurologic score beginning on day 1 by 20%, which persisted throughout weeks 1-3 by 24-41% compared to the saline-treated group. DHA prolonged the latency in rota-rod on weeks 2-3 by 162-178%, enhanced balance performance in the beam walking test on weeks 1 and 2 by 42-51%, and decreased the number of entries in the Y maze test by 51% and spontaneous alteration by 53% on week 2 compared to the saline-treated group. DHA treatment reduced tissue loss (computed from T2-weighted images) by 24% and total and cortical infarct volumes by 46% and 54% compared to the saline-treated group. These results show that DHA confers enduring ischemic neuroprotection. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Effect of Docosahexaenoic Acid Ingestion on Temporal Change in Urinary Excretion of Mercapturic Acid in ODS Rats.

    Science.gov (United States)

    Sekine, Seiji; Kubo, Kazuhiro; Tadokoro, Tadahiro; Saito, Morio

    2007-11-01

    We hypothesized a suppressive mechanism for docosahexaenoic acid (22:6n-3; DHA)-induced tissue lipid peroxidation in which the degradation products, especially aldehydic compounds, are conjugated with glutathione through catalysis by glutathione S-transferases, and then excreted into urine as mercapturic acids. In the present study, ascorbic acid-requiring ODS rats were fed a diet containing DHA (3.6% of total energy) for 31 days. Lipid peroxides including degradation products and their scavengers in the liver and kidney were determined, and the temporal change in the urinary excretion of mercapturic acids was also measured. The activity of aldehyde dehydrogenase, which catalyzes the oxidation and detoxification of aldehydes, tended to be higher in the liver of DHA-fed rats. The levels of lipid peroxides as measured by thiobarbituric acid-reactive substances and aldehydic compounds were higher and that of alpha-tocopherol was lower in the liver, and the pattern of temporal changes in the urinary excretion of mercapturic acids was also different between the n-6 linoleic acid and DHA-fed rats. Accordingly, we presume from these results that after dietary DHA-induced lipid peroxidation, a proportion of the lipid peroxidation-derived aldehydic degradation products is excreted into urine as mercapturic acids.

  8. Circulating docosahexaenoic acid levels are associated with fetal insulin sensitivity.

    Directory of Open Access Journals (Sweden)

    Jin-Ping Zhao

    Full Text Available Arachidonic acid (AA; C20∶4 n-6 and docosahexaenoic acid (DHA; C22∶6 n-3 are important long-chain polyunsaturated fatty acids (LC-PUFA in maintaining pancreatic beta-cell structure and function. Newborns of gestational diabetic mothers are more susceptible to the development of type 2 diabetes in adulthood. It is not known whether low circulating AA or DHA is involved in perinatally "programming" this susceptibility. This study aimed to assess whether circulating concentrations of AA, DHA and other fatty acids are associated with fetal insulin sensitivity or beta-cell function, and whether low circulating concentrations of AA or DHA are involved in compromised fetal insulin sensitivity in gestational diabetic pregnancies.In a prospective singleton pregnancy cohort, maternal (32-35 weeks gestation and cord plasma fatty acids were assessed in relation to surrogate indicators of fetal insulin sensitivity (cord plasma glucose-to-insulin ratio, proinsulin concentration and beta-cell function (proinsulin-to-insulin ratio in 108 mother-newborn pairs. Cord plasma DHA levels (in percentage of total fatty acids were lower comparing newborns of gestational diabetic (n = 24 vs. non-diabetic pregnancies (2.9% vs. 3.5%, P = 0.01. Adjusting for gestational age at blood sampling, lower cord plasma DHA levels were associated with lower fetal insulin sensitivity (lower glucose-to-insulin ratio, r = 0.20, P = 0.036; higher proinsulin concentration, r = -0.37, P <0.0001. The associations remained after adjustment for maternal and newborn characteristics. Cord plasma saturated fatty acids C18∶0 and C20∶0 were negatively correlated with fetal insulin sensitivity, but their levels were not different between gestational diabetic and non-diabetic pregnancies. Cord plasma AA levels were not correlated with fetal insulin sensitivity.Low circulating DHA levels are associated with compromised fetal insulin sensitivity, and may be involved in

  9. Effect of supplementation of arachidonic acid (AA) or a combination of AA plus docosahexaenoic acid on breastmilk fatty acid composition

    NARCIS (Netherlands)

    Smit, EN; Koopmann, M; Boersma, ER; Muskiet, FAJ

    We investigated whether supplementation with arachidonic acid (20:4 omega 6; AA), ora combination of AA and docosahexaenoic acid (22:6 omega 3; DHA) would affect human milk polyunsaturated fatty acid (PUFA) composition. Ten women were daily supplemented with 300 mg AA, eight with 300 mg AA, 110 mg

  10. Intravitreal docosahexaenoic acid in a rabbit model: preclinical safety assessment.

    Directory of Open Access Journals (Sweden)

    Rosa Dolz-Marco

    Full Text Available PURPOSE: The purpose of the present study was to evaluate the retinal toxicity of a single dose of intravitreal docosahexaenoic acid (DHA in rabbit eyes over a short-term period. METHODS: Sixteen New Zealand albino rabbits were selected for this pre-clinical study. Six concentrations of DHA (Brudy Laboratories, Barcelona, Spain were prepared: 10 mg/50 µl, 5 mg/50 µl, 2'5 mg/50 µl, 50 µg/50 µl, 25 µg/50 µl, and 5 µg/50 µl. Each concentration was injected intravitreally in the right eye of two rabbits. As a control, the vehicle solution was injected in one eye of four animals. Retinal safety was studied by slit-lamp examination, and electroretinography. All the rabbits were euthanized one week after the intravitreal injection of DHA and the eyeballs were processed to morphologic and morphometric histological examination by light microscopy. At the same time aqueous and vitreous humor samples were taken to quantify the concentration of omega-3 acids by gas chromatography. Statistical analysis was performed by SPSS 21.0. RESULTS: Slit-lamp examination revealed an important inflammatory reaction on the anterior chamber of the rabbits injected with the higher concentrations of DHA (10 mg/50 µl, 5 mg/50 µl, 2'5 mg/50 µ Lower concentrations showed no inflammation. Electroretinography and histological studies showed no significant difference between control and DHA-injected groups except for the group injected with 50 µg/50 µl. CONCLUSIONS: Our results indicate that administration of intravitreal DHA is safe in the albino rabbit model up to the maximum tolerated dose of 25 µg/50 µl. Further studies should be performed in order to evaluate the effect of intravitreal injection of DHA as a treatment, alone or in combination, of different retinal diseases.

  11. High-oleic ready-to-use therapeutic food maintains docosahexaenoic acid status in severe malnutrition

    Science.gov (United States)

    Ready-to-use therapeutic food (RUTF) is the preferred treatment for uncomplicated severe acute malnutrition. It contains large amounts of linoleic acid and little a-linolenic acid, which may reduce the availability of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to the recovering child...

  12. Dietary docosahexaenoic acid supplementation in children with autism.

    Science.gov (United States)

    Voigt, Robert G; Mellon, Michael W; Katusic, Slavica K; Weaver, Amy L; Matern, Dietrich; Mellon, Bryan; Jensen, Craig L; Barbaresi, William J

    2014-06-01

    The aim of the study was to determine whether docosahexaenoic acid (DHA) supplementation improves the behavior of children with autism. A group of 3- to 10-year-old children with autism were randomized in a double-blind fashion to receive a supplement containing 200 mg of DHA or a placebo for 6 months. The parents and the investigator completed the Clinical Global Impressions-Improvement scale to rate changes in core symptoms of autism after 3 and 6 months. The parents completed the Child Development Inventory and the Aberrant Behavior Checklist, and both parents and teachers completed the Behavior Assessment Scale for Children (BASC) at enrollment and after 6 months. A total of 48 children (40 [83%] boys, mean age [standard deviation] 6.1 [2.0] years) were enrolled; 24 received DHA and 24 placebo. Despite a median 431% increase in total plasma DHA levels after 6 months, the DHA group was not rated as improved in core symptoms of autism compared to the placebo group on the CGI-I. Based on the analysis of covariance models adjusted for the baseline rating scores, parents (but not teachers) provided a higher average rating of social skills on the BASC for the children in the placebo group compared to the DHA group (P = 0.04), and teachers (but not parents) provided a higher average rating of functional communication on the BASC for the children in the DHA group compared to the placebo group (P = 0.02). Dietary DHA supplementation of 200 mg/day for 6 months does not improve the core symptoms of autism. Our results may have been limited by inadequate sample size.

  13. Breast milk docosahexaenoic acid (DHA) correlates with DHA status of malnourished infants

    NARCIS (Netherlands)

    Smit, EN; Oelen, EA; Seerat, E; Muskiet, FAJ; Boersma, ER

    Aim-To investigate whether low docosahexaenoic acid (22:6 omega 3; DHA) status of malnourished, mostly breast fed infants is a result of low omega 3 fatty acid intake via breast milk. Methods-Fatty acid composition of breast milk of eight Pakistani mothers, and of the erythrocytes of their

  14. Raloxifene and hormone replacement therapy increase arachidonic acid and docosahexaenoic levels in postmenopausal women

    NARCIS (Netherlands)

    Giltay, E.J.; Duschek, E.J.J.; Katan, M.B.; Neele, S.J.; Netelenbos, J.C.; Zock, P.L.

    2004-01-01

    Estrogens may affect the essential n-6 and n-3 fatty acids arachidonic acid (AA; C20:4n-6) and docosahexaenoic acid (DHA; C22:6n-3). Therefore, we investigated the long-term effects of hormone replacement therapy and raloxifene, a selective estrogen-receptor modulator, in two randomized,

  15. One-pot synthesis of bioactive cyclopentenones from α-linolenic acid and docosahexaenoic acid.

    Science.gov (United States)

    Maynard, Daniel; Müller, Sara Mareike; Hahmeier, Monika; Löwe, Jana; Feussner, Ivo; Gröger, Harald; Viehhauser, Andrea; Dietz, Karl-Josef

    2018-04-01

    Oxidation products of the poly-unsaturated fatty acids (PUFAs) arachidonic acid, α-linolenic acid and docosahexaenoic acid are bioactive in plants and animals as shown for the cyclopentenones prostaglandin 15d-PGJ 2 and PGA 2 , cis-(+)-12-oxophytodienoic acid (12-OPDA), and 14-A-4 neuroprostane. In this study an inexpensive and simple enzymatic multi-step one-pot synthesis is presented for 12-OPDA, which is derived from α-linolenic acid, and the analogous docosahexaenoic acid (DHA)-derived cyclopentenone [(4Z,7Z,10Z)-12-[[-(1S,5S)-4-oxo-5-(2Z)-pent-2-en-1yl]-cyclopent-2-en-1yl] dodeca-4,7,10-trienoic acid, OCPD]. The three enzymes utilized in this multi-step cascade were crude soybean lipoxygenase or a recombinant lipoxygenase, allene oxide synthase and allene oxide cyclase from Arabidopsis thaliana. The DHA-derived 12-OPDA analog OCPD is predicted to have medicinal potential and signaling properties in planta. With OCPD in hand, it is shown that this compound interacts with chloroplast cyclophilin 20-3 and can be metabolized by 12-oxophytodienoic acid reductase (OPR3) which is an enzyme relevant for substrate bioactivity modulation in planta. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Docosahexaenoic Acid Helps to Lessen Extinction Memory in Rats

    Directory of Open Access Journals (Sweden)

    Michio Hashimoto

    2018-02-01

    Full Text Available Abstract: Memory extinction is referred to as a learning process in which a conditioned response (CR progressively reduces over time as an animal learns to uncouple a response from a stimulus. Extinction occurs when the rat is placed into a context without shock after training. Docosahexaenoic acid (DHA, C22:6, n-3 is implicated in memory formation in mammalian brains. In a two-way active shuttle-avoidance apparatus, we examined whether DHA affects the extinction memory and the expression of brain cognition-related proteins, including gastrin-releasing peptide receptor (GRPR, brain-derived neurotrophic factor receptor (BDNFR tyrosine kinase receptor B (TrKB, and N-methyl-d-aspartate receptor (NMDAR subunits NR2A and NR2B. Also, the protein levels of GRP, BDNF, postsynaptic density protein-95 (PSD-95, and vesicular acetylcholine transporter (VAChT, and the antioxidative potentials, in terms of lipid peroxide (LPO and reactive oxygen species (ROS, were examined in the hippocampus. During the acquisition phase, the rats received a conditioned stimulus (CS-tone paired with an unconditioned stimulus (UCS foot shock for three consecutive days (Sessions S1, S2, and S3, each consisting of 30-trials after 12 weeks of oral administration of DHA. After a three-day interval, the rats were re-subjected to two extinction sessions (S4, S5, each comprising 30 trials of CS alone. During the acquisition training in S1, the shock-related avoidance frequency (acquisition memory was significantly higher in the DHA-administered rats compared with the control rats. The avoidance frequency, however, decreased with successive acquisition trainings in sessions S2 and S3. When the rats were subjected to the extinction sessions after a break for consolidation, the conditioned response (CR was also significantly higher in the DHA-administered rats. Interestingly, the freezing responses (frequency and time also significantly decreased in the DHA-administered rats, thus

  17. Docosahexaenoic acid concentrations are higher in women than in men through estrogenic effects

    NARCIS (Netherlands)

    Giltay, E.J.; Gooren, L.J.G.; Toorians, A.W.F.T.; Katan, M.B.; Zock, P.L.

    2004-01-01

    Background: During pregnancy there is a high demand for docosahexaenoic acid (DHA), which is needed for formation of the fetal brain. Women who do not consume marine foods must synthesize DHA from fatty acid precursors in vegetable foods. Objective: We studied sex differences in DHA status and the

  18. Polymorphisms in the fatty acid desaturase genes and diet are important determinants of infant docosahexaenoic acid status

    DEFF Research Database (Denmark)

    Lauritzen, L.; Harsløf, L.; Larsen, L.H.

    2013-01-01

    Tissue docosahexaenoic acid (DHA) accretion in early infancy is supported by DHA in breast-milk and may thus decrease once complementary feeding takes over. Endogenous synthesis of DHA from alphalinolenic acid is low and polymorphisms in the genes that encodes the fatty acid desaturases (FADS) ha...

  19. The Conjugate Acid-Base Chart.

    Science.gov (United States)

    Treptow, Richard S.

    1986-01-01

    Discusses the difficulties that beginning chemistry students have in understanding acid-base chemistry. Describes the use of conjugate acid-base charts in helping students visualize the conjugate relationship. Addresses chart construction, metal ions, buffers and pH titrations, and the organic functional groups and nonaqueous solvents. (TW)

  20. Docosahexaenoic acid and n-6 docosapentaenoic acid supplementation alter rat skeletal muscle fatty acid composition

    Directory of Open Access Journals (Sweden)

    Lim Sun-Young

    2007-04-01

    Full Text Available Abstract Background Docosahexaenoic acid (22:6n-3, DHA and n-6 docosapentaenoic acid (22:5n-6, DPAn-6 are highly unsaturated fatty acids (HUFA, ≥ 20 carbons, ≥ 3 double bonds that differ by a single carbon-carbon double bond at the Δ19 position. Membrane 22:6n-3 may support skeletal muscle function through optimal ion pump activity of sarcoplasmic reticulum and electron transport in the mitochondria. Typically n-3 fatty acid deficient feeding trials utilize linoleic acid (18:2n-6, LA as a comparison group, possibly introducing a lower level of HUFA in addition to n-3 fatty acid deficiency. The use of 22:5n-6 as a dietary control is ideal for determining specific requirements for 22:6n-3 in various physiological processes. The incorporation of dietary 22:5n-6 into rat skeletal muscles has not been demonstrated previously. A one generation, artificial rearing model was utilized to supply 22:6n-3 and/or 22:5n-6 to rats from d2 after birth to adulthood. An n-3 fatty acid deficient, artificial milk with 18:2n-6 was supplemented with 22:6n-3 and/or 22:5n-6 resulting in four artificially reared (AR dietary groups; AR-LA, AR-DHA, AR-DPAn-6, AR-DHA+DPAn-6. A dam reared group (DAM was included as an additional control. Animals were sacrificed at 15 wks and soleus, white gastrocnemius and red gastrocnemius muscles were collected for fatty acid analyses. Results In all muscles of the DAM group, the concentration of 22:5n-6 was significantly lower than 22:6n-3 concentrations. While 22:5n-6 was elevated in the AR-LA group and the AR-DPAn-6 group, 20:4n-6 tended to be higher in the AR-LA muscles and not in the AR-DPAn-6 muscles. The AR-DHA+DPAn-6 had a slight, but non-significant increase in 22:5n-6 content. In the red gastrocnemius of the AR-DPAn-6 group, 22:5n-6 levels (8.1 ± 2.8 wt. % did not reciprocally replace the 22:6n-3 levels observed in AR-DHA reared rats (12.2 ± 2.3 wt. % suggesting a specific preference/requirement for 22:6n-3 in red

  1. Effects of dietary conjugated linoleic acid and linoleic:linolenic acid ratio on polyunsaturated fatty acid status in laying hens.

    Science.gov (United States)

    Du, M; Ahn, D U; Sell, J L

    2000-12-01

    A study was conducted to determine the effects of dietary conjugated linoleic acid (CLA) and the ratio of linoleic:linolenic acid on long-chain polyunsaturated fatty acid status. Thirty-two 31-wk-old White Leghorn hens were randomly assigned to four diets containing 8.2% soy oil, 4.1% soy oil + 2.5% CLA (4.1% CLA source), 4.1% flax oil + 2.5% CLA, or 4.1% soy oil + 4.1% flax oil. Hens were fed the diets for 3 wk before eggs and tissues were collected for the study. Lipids were extracted from egg yolk and tissues, classes of egg yolk lipids were separated, and fatty acid concentrations of total lipids, triglyceride, phosphatidylethanolamine, and phosphatidylcholine were analyzed by gas chromatography. The concentrations of monounsaturated fatty acids and non-CLA polyunsaturated fatty acids were reduced after CLA feeding. The amount of arachidonic acid was decreased after CLA feeding in linoleic acid- and linolenic acid-rich diets, but amounts of eicosapentaenoic acid and docosahexaenoic acid were increased in the linolenic-rich diet, indicating that the synthesis or deposition of long-chain n-3 fatty acids was accelerated after CLA feeding. The increased docosahexaenoic acid and eicosapentaenoic acid contents in lipid may be compensation for the decreased arachidonic acid content. Dietary supplementation of linoleic acid increased n-6 fatty acid levels in lipids, whereas linolenic acid increased n-3 fatty acid levels. Results also suggest that CLA might not be elongated to synthesize long-chain fatty acids in significant amounts. The effect of CLA in reducing the level of n-6 fatty acids and promoting the level of n-3 fatty acids could be related to the biological effects of CLA.

  2. Feeding nitrate and docosahexaenoic acid affects enteric methane production and milk fatty acid composition in lactating dairy cows

    NARCIS (Netherlands)

    Klop, G.; Hatew, B.; Bannink, A.; Dijkstra, Jan

    2016-01-01

    An experiment was conducted to study potential interaction between the effects of feeding nitrate and docosahexaenoic acid (DHA; C22:6 n-3) on enteric CH4 production and performance of lactating dairy cows. Twenty-eight lactating Holstein dairy cows were grouped into 7 blocks of 4

  3. Docosahexaenoic acid levels in blood and metabolic syndrome in obese children: is there a link?

    OpenAIRE

    Lassandro, C.; Banderali, G.; Radaelli, G.; Borghi, E.; Moretti, F.; Verduci, E.

    2015-01-01

    Prevalence of metabolic syndrome is increasing in the pediatric population. Considering the different existing criteria to define metabolic syndrome, the use of the International Diabetes Federation (IDF) criteria has been suggested in children. Docosahexaenoic acid (DHA) has been associated with beneficial effects on health. The evidence about the relationship of DHA status in blood and components of the metabolic syndrome is unclear. This review discusses the possible association between DH...

  4. Lowering dietary n-6 polyunsaturated fatty acids: interaction with brain arachidonic and docosahexaenoic acids.

    Science.gov (United States)

    Alashmali, Shoug M; Hopperton, Kathryn E; Bazinet, Richard P

    2016-02-01

    Arachidonic (ARA) and docosahexaenoic (DHA) acids are the most abundant polyunsaturated fatty acids (PUFA) in the brain, where they have many biological effects, including on inflammation, cell-signaling, appetite regulation, and blood flow. The Western diet contains a high ratio of n-6: n-3 PUFA. Although interest in lowering this ratio has largely focused on increasing intake of n-3 PUFA, few studies have examined lowering dietary n-6 PUFA. This review will evaluate the effect of lowering dietary n-6 PUFA on levels and metabolism of ARA and DHA in animal models and in humans, with a primary focus on the brain. In animal models, lowering dietary ARA or linoleic acid generally lowers levels of brain ARA and raises DHA. Lowering dietary n-6 PUFA can also modulate the levels of ARA and DHA metabolizing enzymes, as well as their associated bioactive mediators. Human studies examining changes in plasma fatty acid composition following n-6 PUFA lowering demonstrate no changes in levels of ARA and DHA, though there is evidence of alterations in their respective bioactive mediators. Lowering dietary n-6 PUFA, in animal models, can alter the levels and metabolism of ARA and DHA in the brain, but it remains to be determined whether these changes are clinically meaningful.

  5. Early postnatal docosahexaenoic acid levels and improved preterm brain development

    OpenAIRE

    Tam, Emily W.Y.; Chau, Vann; Barkovich, A. James; Ferriero, Donna M.; Miller, Steven P.; Rogers, Elizabeth E.; Grunau, Ruth E.; Synnes, Anne R.; Xu, Duan; Foong, Justin; Brant, Rollin; Innis, Sheila M.

    2016-01-01

    Background Preterm birth has a dramatic impact on polyunsaturated fatty acid exposures for the developing brain. This study examined the association between postnatal fatty acid levels and measures of brain injury and development, as well as outcomes. Methods A cohort of 60 preterm newborns (24?32 weeks GA) was assessed using early and near-term MRI studies. Red blood cell fatty acid composition was analyzed coordinated with each scan. Outcome at a mean of 33 months corrected age was assessed...

  6. Targeting inflammation in the preterm infant: The role of the omega-3 fatty acid docosahexaenoic acid

    Directory of Open Access Journals (Sweden)

    Naomi H. Fink

    2016-09-01

    Full Text Available Long-chain polyunsaturated fatty acids are critical for the normal growth and development of preterm infants. Interest in these compounds rests in their anti-inflammatory properties. Clinical conditions with an inflammatory component such as bronchopulmonary dysplasia, necrotising enterocolitis and sepsis are risks to the survival of these infants. Dysregulation of inflammatory responses plays a central role in the aetiology of many of these neonatal disorders. There is evidence to suggest that the omega-3 long chain polyunsaturated fatty acid docosahexaenoic acid (DHA can down-regulate local and systemic inflammation in adults and animal models; however, very little is known about its protective effects in infants, especially preterm infants. Due to their immunological immaturity, preterm infants are particularly sensitive to diseases with an inflammatory aetiology in the early postnatal period. This makes DHA supplementation immediately after birth to combat neonatal inflammation an attractive therapy. Mechanistic data for DHA use in preterm infants are lacking and results from adult and animal studies may not be relevant to this population because of fundamental immune system differences. While there is increasing evidence from randomised controlled trials to support a beneficial effect of DHA for the preterm infant, more evidence is required to establish short and long-term effects of DHA on the immune status of preterm infants.

  7. Docosahexaenoic acid (DHA), a fundamental fatty acid for the brain: New dietary sources.

    Science.gov (United States)

    Echeverría, Francisca; Valenzuela, Rodrigo; Catalina Hernandez-Rodas, María; Valenzuela, Alfonso

    2017-09-01

    Docosahexaenoic acid (C22: 6n-3, DHA) is a long-chain polyunsaturated fatty acid of marine origin fundamental for the formation and function of the nervous system, particularly the brain and the retina of humans. It has been proposed a remarkable role of DHA during human evolution, mainly on the growth and development of the brain. Currently, DHA is considered a critical nutrient during pregnancy and breastfeeding due their active participation in the development of the nervous system in early life. DHA and specifically one of its derivatives known as neuroprotectin D-1 (NPD-1), has neuroprotective properties against brain aging, neurodegenerative diseases and injury caused after brain ischemia-reperfusion episodes. This paper discusses the importance of DHA in the human brain given its relevance in the development of the tissue and as neuroprotective agent. It is also included a critical view about the ways to supply this noble fatty acid to the population. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. The Differential Effects of Eicosapentaenoic Acid and Docosahexaenoic Acid on Cardiometabolic Risk Factors: A Systematic Review

    Science.gov (United States)

    Innes, Jacqueline K.; Calder, Philip C.

    2018-01-01

    A large body of evidence supports the cardioprotective effects of the long-chain omega-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). There is increasing interest in the independent effects of EPA and DHA in the modulation of cardiometabolic risk factors. This systematic review aims to appraise the latest available evidence of the differential effects of EPA and DHA on such risk factors. A systematic literature review was conducted up to May 2017. Randomised controlled trials were included if they met strict eligibility criteria, including EPA or DHA > 2 g/day and purity ≥ 90%. Eighteen identified articles were included, corresponding to six unique studies involving 527 participants. Both EPA and DHA lowered triglyceride concentration, with DHA having a greater triglyceride-lowering effect. Whilst total cholesterol levels were largely unchanged by EPA and DHA, DHA increased high-density lipoprotein (HDL) cholesterol concentration, particularly HDL2, and increased low-density lipoprotein (LDL) cholesterol concentration and LDL particle size. Both EPA and DHA inhibited platelet activity, whilst DHA improved vascular function and lowered heart rate and blood pressure to a greater extent than EPA. The effects of EPA and DHA on inflammatory markers and glycaemic control were inconclusive; however both lowered oxidative stress. Thus, EPA and DHA appear to have differential effects on cardiometabolic risk factors, but these need to be confirmed by larger clinical studies. PMID:29425187

  9. Docosahexaenoic acid and other fatty acids induce a decrease in pHi in Jurkat T-cells

    OpenAIRE

    Aires, Virginie; Hichami, Aziz; Moutairou, Kabirou; Khan, Naim Akhtar

    2003-01-01

    Docosahexaenoic acid (DHA) induced rapid (t1/2=33 s) and dose-dependent decreases in pHi in BCECF-loaded human (Jurkat) T-cells. Addition of 5-(N,N-dimethyl)-amiloride, an inhibitor of Na+/H+ exchanger, prolonged DHA-induced acidification as a function of time, indicating that the exchanger is implicated in pHi recovery.Other fatty acids like oleic acid, arachidonic acid, eicosapentaenoic acid, but not palmitic acid, also induced a fall in pHi in these cells.To assess the role of calcium in t...

  10. Maternal and fetal brain contents of docosahexaenoic acid (DHA) and arachidonic acid (AA) at various essential fatty acid (EFA), DHA and AA dietary intakes during pregnancy in mice

    NARCIS (Netherlands)

    van Goor, Saskia A; Dijck-Brouwer, D A Janneke; Fokkema, M Rebecca; van der Iest, Theo Hans; Muskiet, Frits A J

    We investigated essential fatty acids (EFA) and long-chain polyunsaturated fatty acids (LCP) in maternal and fetal brain as a function of EFA/LCP availability to the feto-maternal unit in mice. Diets varying in parent EFA, arachidonic acid (AA), and docosahexaenoic acid (DHA) were administered from

  11. Gas chromatography/mass spectrometry analysis of very long chain fatty acids, docosahexaenoic acid, phytanic acid and plasmalogen for the screening of peroxisomal disorders

    NARCIS (Netherlands)

    Takemoto, Yasuhiko; Suzuki, Yasuyuki; Horibe, Ryoko; Shimozawa, Nobuyuki; Wanders, Ronald J. A.; Kondo, Naomi

    2003-01-01

    Very long chain fatty acids (VLCFAs) and docosahexaenoic acid (DHA), phytanic acid, and plasmalogens are usually measured individually. A novel method for the screening of peroxisomal disorders, using gas chromatography/mass spectrometry (GC/MS), was developed. Saturated and unsaturated fatty acids,

  12. Treatment with Docosahexaenoic Acid, but Not Eicosapentaenoic Acid, Delays Ca2+-Induced Mitochondria Permeability Transition in Normal and Hypertrophied Myocardium

    OpenAIRE

    Khairallah, Ramzi J.; O'Shea, Karen M.; Brown, Bethany H.; Khanna, Nishanth; Des Rosiers, Christine; Stanley, William C.

    2010-01-01

    Intake of fish oil containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) prevents heart failure; however, the mechanisms are unclear. Mitochondrial permeability transition pore (MPTP) opening contributes to myocardial pathology in cardiac hypertrophy and heart failure, and treatment with DHA + EPA delays MPTP opening. Here, we assessed: 1) whether supplementation with both DHA and EPA is needed for optimal prevention of MPTP opening, and 2) whether this benefit occurs in hyper...

  13. Is docosahexaenoic acid synthesis from α-linolenic acid sufficient to supply the adult brain?

    Science.gov (United States)

    Domenichiello, Anthony F; Kitson, Alex P; Bazinet, Richard P

    2015-07-01

    Docosahexaenoic acid (DHA) is important for brain function, and can be obtained directly from the diet or synthesized in the body from α-linolenic acid (ALA). Debate exists as to whether DHA synthesized from ALA can provide sufficient DHA for the adult brain, as measures of DHA synthesis from ingested ALA are typically <1% of the oral ALA dose. However, the primary fate of orally administered ALA is β-oxidation and long-term storage in adipose tissue, suggesting that DHA synthesis measures involving oral ALA tracer ingestion may underestimate total DHA synthesis. There is also evidence that DHA synthesized from ALA can meet brain DHA requirements, as animals fed ALA-only diets have brain DHA concentrations similar to DHA-fed animals, and the brain DHA requirement is estimated to be only 2.4-3.8 mg/day in humans. This review summarizes evidence that DHA synthesis from ALA can provide sufficient DHA for the adult brain by examining work in humans and animals involving estimates of DHA synthesis and brain DHA requirements. Also, an update on methods to measure DHA synthesis in humans is presented highlighting a novel approach involving steady-state infusion of stable isotope-labeled ALA that bypasses several limitations of oral tracer ingestion. It is shown that this method produces estimates of DHA synthesis that are at least 3-fold higher than brain uptake rates in rats. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. The influence of supplemental docosahexaenoic and arachidonic acids during pregnancy and lactation on neurodevelopment at eighteen months

    NARCIS (Netherlands)

    van Goor, Saskia A.; Dijck-Brouwer, D. A. Janneke; Erwich, Jan Jaap H. M.; Schaafsma, Anne; Hadders-Algra, Mijna

    2011-01-01

    Docosahexaenoic acid (DHA) and arachidonic acid (AA) are important for neurodevelopment. The effects of DHA (220 mg/day, n=41), DHA+AA (220 mg/day, n=39) or placebo (n=34) during pregnancy and lactation on neurodevelopment at 18 months, and the relations between umbilical cord DHA, AA and Mead acid

  15. The potential relevance of docosahexaenoic acid and eicosapentaenoic acid to the etiopathogenesis of childhood neuropsychiatric disorders.

    Science.gov (United States)

    Tesei, Alessandra; Crippa, Alessandro; Ceccarelli, Silvia Busti; Mauri, Maddalena; Molteni, Massimo; Agostoni, Carlo; Nobile, Maria

    2017-09-01

    Over the last 15 years, considerable interest has been given to the potential role of omega-3 polyunsaturated fatty acids (PUFAs) for understanding pathogenesis and treatment of neurodevelopmental and psychiatric disorders. This review aims to systematically investigate the scientific evidence supporting the hypothesis on the omega-3 PUFAs deficit as a risk factor shared by different pediatric neuropsychiatric disorders. Medline PubMed database was searched for studies examining blood docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) status in children with neuropsychiatric disorders. Forty-one published manuscripts were compatible with the search criteria. The majority of studies on attention-deficit/hyperactivity disorder (ADHD) and autism found a significant decrease in DHA levels in patients versus healthy controls. For the other conditions examined-depression, juvenile bipolar disorder, intellectual disabilities, learning difficulties, and eating disorders (EDs)-the literature was too limited to draw any stable conclusions. However, except EDs, findings in these conditions were in line with results from ADHD and autism studies. Results about EPA levels were too inconsistent to conclude that EPA could be associated with any of the conditions examined. Finally, correlational data provided, on one hand, evidence for a negative association between DHA and symptomatology, whereas on the other hand, evidence for a positive association between EPA and emotional well-being. Although the present review underlines the potential involvement of omega-3 PUFAs in the predisposition to childhood neuropsychiatric disorders, more observational and intervention studies across different diagnoses are needed, which should integrate the collection of baseline PUFA levels with their potential genetic and environmental influencing factors.

  16. Dietary docosahexaenoic acid (DHA) as lysophosphatidylcholine, but not as free acid, enriches brain DHA and improves memory in adult mice

    OpenAIRE

    Sugasini, Dhavamani; Thomas, Riya; Yalagala, Poorna C. R.; Tai, Leon M.; Subbaiah, Papasani V.

    2017-01-01

    Docosahexaenoic acid (DHA) is uniquely concentrated in the brain, and is essential for its function, but must be mostly acquired from diet. Most of the current supplements of DHA, including fish oil and krill oil, do not significantly increase brain DHA, because they are hydrolyzed to free DHA and are absorbed as triacylglycerol, whereas the transporter at blood brain barrier is specific for phospholipid form of DHA. Here we show that oral administration of DHA to normal adult mice as lysopho...

  17. Draft genome sequence of the docosahexaenoic acid producing thraustochytrid Aurantiochytrium sp. T66

    Directory of Open Access Journals (Sweden)

    Bin Liu

    2016-06-01

    Full Text Available Thraustochytrids are unicellular, marine protists, and there is a growing industrial interest in these organisms, particularly because some species, including strains belonging to the genus Aurantiochytrium, accumulate high levels of docosahexaenoic acid (DHA. Here, we report the draft genome sequence of Aurantiochytrium sp. T66 (ATCC PRA-276, with a size of 43 Mbp, and 11,683 predicted protein-coding sequences. The data has been deposited at DDBJ/EMBL/Genbank under the accession LNGJ00000000. The genome sequence will contribute new insight into DHA biosynthesis and regulation, providing a basis for metabolic engineering of thraustochytrids.

  18. Chronic sucrose intake decreases concentrations of n6 fatty acids, but not docosahexaenoic acid in the rat brain phospholipids.

    Science.gov (United States)

    Mašek, Tomislav; Starčević, Kristina

    2017-07-13

    We investigated the influence of high sucrose intake, administered in drinking water, on the lipid profile of the brain and on the expression of SREBP1c and Δ-desaturase genes. Adult male rats received 30% sucrose solution for 20 weeks (Sucrose group), or plain water (Control group). After the 20th week of sucrose treatment, the Sucrose group showed permanent hyperglycemia. Sucrose treatment also increased the amount of total lipids and fatty acids in the brain. The brain fatty acid profile of total lipids as well as phosphatidylethanolamine, phosphatidylcholine and cardiolipin of the Sucrose group was extensively changed. The most interesting change was a significant decrease in n6 fatty acids, including the important arachidonic acid, whereas the content of oleic and docosahexaenoic acid remained unchanged. RT-qPCR revealed an increase in Δ-5-desaturase and SREBP1c gene expression. In conclusion, high sucrose intake via drinking water extensively changes rat brain fatty acid profile by decreasing n6 fatty acids, including arachidonic acid. In contrast, the content of docosahexaenoic acid remains constant in the brain total lipids as well as in phospholipids. Changes in the brain fatty acid profile reflect changes in the lipid metabolism of the rat lipogenic tissues and concentrations in the circulation. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Long-Term Effects of Docosahexaenoic Acid-Bound Phospholipids and the Combination of Docosahexaenoic Acid-Bound Triglyceride and Egg Yolk Phospholipid on Lipid Metabolism in Mice

    Science.gov (United States)

    Che, Hongxia; Cui, Jie; Wen, Min; Xu, Jie; Yanagita, Teruyoshi; Wang, Qi; Xue, Changhu; Wang, Yuming

    2018-04-01

    The bioavailability of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) depends on their chemical forms. This study investigated the long-term effects of DHA-bound triglyceride (TG-DHA), DHA-bound phospholipid (PL-DHA), and the combination of TG-DHA and egg yolk phospholipid (Egg-PL) on lipid metabolism in mice fed with a high-fat diet (fat levels of 22.5%). Male C57BL/6J mice were fed with different formulations containing 0.5% DHA, including TG-DHA, PL-DHA, and the combination of TG-DHA and Egg-PL, for 6 weeks. Serum, hepatic, and cerebral lipid concentrations and the fatty acid compositions of the liver and brain were determined. The concentrations of serum total triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), and hepatic TG in the PL-DHA group and the combination group were significantly lower than those in the high-fat (HF) group ( P Egg-PL in decreasing the AI. Long-term dietary supplementation with low amount of DHA (0.5%) may improve hepatic DHA levels, although cerebral DHA levels may not be enhanced.

  20. Docosahexaenoic acid (DHA) and arachidonic acid (ARA) balance in developmental outcomes.

    Science.gov (United States)

    Colombo, John; Jill Shaddy, D; Kerling, Elizabeth H; Gustafson, Kathleen M; Carlson, Susan E

    2017-06-01

    The DHA Intake and Measurement of Neural Development (DIAMOND) trial represents one of only a few studies of the long-term dose-response effects of LCPUFA-supplemented formula feeding during infancy. The trial contrasted the effects of four formulations: 0.00% docosahexaenoic acid (DHA)/0.00% arachidonic acid (ARA), 0.32% DHA/0.64% ARA, 0.64% DHA/0.64% ARA, and 0.96% DHA/0.64% ARA against a control condition (0.00% DHA/0.00% ARA). The results of this trial have been published elsewhere, and show improved cognitive outcomes for infants fed supplemented formulas, but a common finding among many of the outcomes show a reduction of benefit for the highest DHA dose (i.e., 0.96%DHA/0.64% ARA, that is, a DHA: ARA ratio 1.5:1.0). The current paper gathers and summarizes the evidence for the reduction of benefit at this dose, and in an attempt to account for this reduced benefit, presents for the first time data from infants' red blood cell (RBC) assays taken at 4 and 12 months of age. Those assays indicate that blood DHA levels generally rose with increased DHA supplementation, although those levels tended to plateau as the DHA-supplemented level exceeded 0.64%. Perhaps more importantly, ARA levels showed a strong inverted-U function in response to increased DHA supplementation; indeed, infants assigned to the formula with the highest dose of DHA (and highest DHA/ARA ratio) showed a reduction in blood ARA relative to more intermediate DHA doses. This finding raises the possibility that reduced ARA may be responsible for the reduction in benefit on cognitive outcomes seen at this dose. The findings implicate the DHA/ARA balance as an important variable in the contribution of LCPUFAs to cognitive and behavioral development in infancy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Effect of docosahexaenoic acid and ascorbate on peroxidation of retinal membranes of ODS rats.

    Science.gov (United States)

    Wang, Jin-Ye; Sekine, Seiji; Saito, Morio

    2003-04-01

    Mutant male osteogenic disorder Shionogi (ODS) rats, unable to synthesize ascorbic acid, were fed diets containing a high content of docosahexaenoic acid (DHA) and different amounts of ascorbic acid, to study the effect of DHA on peroxidative susceptibility of the retina and possible antioxidant action of ascorbic acid. ODS rats were fed from 7 weeks of age with diets containing high DHA (6.4% of total energy). A control group received a diet high in linoleic acid. The diets also contained varying amounts of ascorbic acid. Fatty acid compositions and phospholipid hydroperoxides in rod outer segment (ROS) membranes, and retinal ascorbic acid were analyzed. DHA in ROS membranes was significantly increased in rats fed high DHA, compared with the linoleic acid diet. Levels of phospholipid hydroperoxides in the DHA-fed rats were significantly higher than the linoleic acid-fed rats. Ascorbic acid supplementation did not suppress the phospholipid hydroperoxide levels after a high DHA diet, even when the supplement increased the content of retinal ascorbic acid. In conclusion, high DHA feeding induced a marked increase of phospholipid hydroperoxides in ROS membranes of ODS rats. Supplementation of ascorbic acid did not reverse this increase.

  2. Emotional based cognition in mice is differentially influenced by dose and lipid origin of dietary docosahexaenoic acid

    Science.gov (United States)

    Docosahexaenoic acid (DHA) is a major constituent, and primary omega-3 fatty acid, in the brain. Evidence suggests that DHA consumption may promote cognitive functioning and prevent cognitive decline, and these effects may be particularly relevant in the context of fear or stress. However, the pot...

  3. Serum n-3 Tetracosapentaenoic Acid and Tetracosahexaenoic Acid Increase Following Higher Dietary α-Linolenic Acid but not Docosahexaenoic Acid.

    Science.gov (United States)

    Metherel, Adam H; Domenichiello, Anthony F; Kitson, Alex P; Lin, Yu-Hong; Bazinet, Richard P

    2017-02-01

    n-3 Tetracosapentaenoic acid (24:5n-3, TPAn-3) and tetracosahexaenoic acid (24:6n-3, THA) are believed to be important intermediates to docosahexaenoic acid (DHA, 22:6n-3) synthesis. The purpose of this study is to report for the first time serum concentrations of TPAn-3 and THA and their response to changing dietary α-linolenic acid (18:3n-3, ALA) and DHA. The responses will then be used in an attempt to predict the location of these fatty acids in relation to DHA in the biosynthetic pathway. Male Long Evans rats (n = 6 per group) were fed either a low (0.1% of total fatty acids), medium (3%) or high (10%) ALA diet with no added DHA, or a low (0%), medium (0.2%) or high (2%) DHA diet with a background of 2% ALA for 8 weeks post-weaning. Serum n-3 and n-6 polyunsaturated fatty acid (PUFA) concentrations (nmol/mL ± SEM) were determined by gas chromatography-mass spectrometry. Serum THA increases from low (0.3 ± 0.1) to medium (5.8 ± 0.7) but not from medium to high (4.6 ± 0.9) dietary ALA, while serum TPAn-3 increases with increasing dietary ALA from 0.09 ± 0.04 to 0.70 ± 0.09 to 1.23 ± 0.14 nmol/mL. Following DHA feeding, neither TPAn-3 or THA change across all dietary DHA intake levels. Serum TPAn-3 demonstrates a similar response to dietary DHA. In conclusion, this is the first study to demonstrate that increases in dietary ALA but not DHA increase serum TPAn-3 and THA in rats, suggesting that both fatty acids are precursors to DHA in the biosynthetic pathway.

  4. Docosahexaenoic Acid-Derived Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs) With Anti-inflammatory Properties.

    Science.gov (United States)

    Kuda, Ondrej; Brezinova, Marie; Rombaldova, Martina; Slavikova, Barbora; Posta, Martin; Beier, Petr; Janovska, Petra; Veleba, Jiri; Kopecky, Jan; Kudova, Eva; Pelikanova, Terezie; Kopecky, Jan

    2016-09-01

    White adipose tissue (WAT) is a complex organ with both metabolic and endocrine functions. Dysregulation of all of these functions of WAT, together with low-grade inflammation of the tissue in obese individuals, contributes to the development of insulin resistance and type 2 diabetes. n-3 polyunsaturated fatty acids (PUFAs) of marine origin play an important role in the resolution of inflammation and exert beneficial metabolic effects. Using experiments in mice and overweight/obese patients with type 2 diabetes, we elucidated the structures of novel members of fatty acid esters of hydroxy fatty acids-lipokines derived from docosahexaenoic acid (DHA) and linoleic acid, which were present in serum and WAT after n-3 PUFA supplementation. These compounds contained DHA esterified to 9- and 13-hydroxyoctadecadienoic acid (HLA) or 14-hydroxydocosahexaenoic acid (HDHA), termed 9-DHAHLA, 13-DHAHLA, and 14-DHAHDHA, and were synthesized by adipocytes at concentrations comparable to those of protectins and resolvins derived from DHA in WAT. 13-DHAHLA exerted anti-inflammatory and proresolving properties while reducing macrophage activation by lipopolysaccharides and enhancing the phagocytosis of zymosan particles. Our results document the existence of novel lipid mediators, which are involved in the beneficial anti-inflammatory effects attributed to n-3 PUFAs, in both mice and humans. © 2016 by the American Diabetes Association.

  5. Considerations for incorporating eicosapentaenoic and docosahexaenoic omega-3 fatty acids into the military food supply chain.

    Science.gov (United States)

    Ismail, Adam; Rice, Harry B

    2014-11-01

    The U.S. military may consider exploring the inclusion of the long-chain omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in the diets of active duty military personnel. To be successful, certain challenges must be overcome including determining appropriate dosage, ensuring cost efficiency, and optimizing stability. To increase EPA and DHA intake, the military should consider using one of three strategies, including mandates or recommendations on omega-3 supplement usage, contracts to purchase commercially available foods for distribution in the food supply chain, or direct addition of EPA and DHA into currently consumed foods. This review presents the challenges and strategies and provides potential suggestions to the military to increase the likelihood of success. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

  6. Antibacterial and antibiofilm activities of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) against periodontopathic bacteria.

    Science.gov (United States)

    Sun, Mengjun; Zhou, Zichao; Dong, Jiachen; Zhang, Jichun; Xia, Yiru; Shu, Rong

    2016-10-01

    Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are two major omega-3 polyunsaturated fatty acids (n-3 PUFAs) with antimicrobial properties. In this study, we evaluated the potential antibacterial and antibiofilm activities of DHA and EPA against two periodontal pathogens, Porphyromonas gingivalis (P. gingivalis) and Fusobacterium nucleatum (F. nucleatum). MTT assay showed that DHA and EPA still exhibited no cytotoxicity to human oral tissue cells when the concentration came to 100 μM and 200 μM, respectively. Against P. gingivalis, DHA and EPA showed the same minimum inhibitory concentration (MIC) of 12.5 μM, and a respective minimum bactericidal concentration (MBC) of 12.5 μM and 25 μM. However, the MIC and MBC values of DHA or EPA against F. nucleatum were both greater than 100 μM. For early-stage bacteria, DHA or EPA displayed complete inhibition on the planktonic growth and biofilm formation of P. gingivalis from the lowest concentration of 12.5 μM. And the planktonic growth of F. nucleatum was slightly but not completely inhibited by DHA or EPA even at the concentration of 100 μM, however, the biofilm formation of F. nucleatum at 24 h was significantly restrained by 100 μM EPA. For exponential-phase bacteria, 100 μM DHA or EPA completely killed P. gingivalis and significantly decreased the viable counts of F. nucleatum. Meanwhile, the morphology of P. gingivalis was apparently damaged, and the virulence factor gene expression of P. gingivalis and F. nucleatum was strongly downregulated. Besides, the viability and the thickness of mature P. gingivalis biofilm, together with the viability of mature F. nucleatum biofilm were both significantly decreased in the presence of 100 μM DHA or EPA. In conclusion, DHA and EPA possessed antibacterial activities against planktonic and biofilm forms of periodontal pathogens, which suggested that DHA and EPA might be potentially supplementary therapeutic agents for prevention

  7. Conjugated Linoleic Acid: good or bad nutrient

    Directory of Open Access Journals (Sweden)

    Gonçalves Daniela C

    2010-10-01

    Full Text Available Abstract Conjugated linoleic acid (CLA is a class of 28 positional and geometric isomers of linoleic acid octadecadienoic.Currently, it has been described many benefits related to the supplementation of CLA in animals and humans, as in the treatment of cancer, oxidative stress, in atherosclerosis, in bone formation and composition in obesity, in diabetes and the immune system. However, our results show that, CLA appears to be not a good supplement in patients with cachexia.

  8. A dose response randomised controlled trial of docosahexaenoic acid (DHA) in preterm infants.

    Science.gov (United States)

    Collins, C T; Sullivan, T R; McPhee, A J; Stark, M J; Makrides, M; Gibson, R A

    2015-08-01

    Thirty one infants born less than 30 weeks׳ gestational age were randomised to receive either 40 (n=11), 80 (n=9) or 120 (n=11) mg/kg/day of docosahexaenoic acid (DHA) respectively as an emulsion, via the feeding tube, commenced within 4 days of the first enteral feed. Twenty three infants were enroled in non-randomised reference groups; n=11 who had no supplementary DHA and n=12 who had maternal DHA supplementation. All levels of DHA in the emulsion were well tolerated with no effect on number of days of interrupted feeds or days to full enteral feeds. DHA levels in diets were directly related to blood DHA levels but were unrelated to arachidonic acid (AA) levels. All randomised groups and the maternal supplementation reference group prevented the drop in DHA levels at study end that was evident in infants not receiving supplementation. Australian New Zealand Clinical Trials Registry: ACTRN12610000382077. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. PENGARUH DOCOSAHEXAENOIC ACID (DHA PADA TUMBUH KEMBANG ANAK BALITA GIZI BURUK YANG DIRAWAT JALAN [The effect of DocosaHexaenoic Acid (DHA on growth and development of outpatient rehabilitation of children under-five with severe malnutrition

    Directory of Open Access Journals (Sweden)

    Astuti Lamid1, , , , dan

    2002-12-01

    Full Text Available The study examined the effect of DocosaHexaenoic Acid (DHA on growth and development of outpatient rehabilitation of children under five with severe malnutrition. Sample was children whose age from 6 to 24 months suffering from severe malnutrition with weight /age index of WHO standard of Z score 0,05.

  10. [The effect of docosahexaenoic acid on the loss of appetite in pediatric patients with pneumonia].

    Science.gov (United States)

    López-Alarcón, Mardya; Furuya-Meguro, María Magdalena; García-Zúñiga, Pedro Alberto; Tadeo-Pulido, Irsa

    2006-01-01

    To evaluate the role of docosahexaenoic acid (DHA) administered during the acute phase of pneumonia in infants, on appetite, cytokines and leptin concentrations. Seventeen children between three months and 12 years of age were followed from hospitalization to discharge. Children were randomly assigned to receive DHA or placebo. The effect of treatment was evaluated on energy intake, cytokines, and leptin concentrations. Cytokine concentrations tended to decrease earlier in DHA children. By day 4, concentrations of IL-1beta and TNFalpha had decreased by 12%, while such concentrations increased by 12% and 250% in placebo children. Energy intake recovered in DHA children at discharge, but placebo children were still consuming only 60% of their requirements. Our results suggest that DHA administered in the acute phase of infection could modulate IL-1 and TNF production, and secondarily, decrease the effect of infection on appetite.

  11. Docosahexaenoic Acid Levels in Blood and Metabolic Syndrome in Obese Children: Is There a Link?

    Science.gov (United States)

    Lassandro, Carlotta; Banderali, Giuseppe; Radaelli, Giovanni; Borghi, Elisa; Moretti, Francesca; Verduci, Elvira

    2015-08-21

    Prevalence of metabolic syndrome is increasing in the pediatric population. Considering the different existing criteria to define metabolic syndrome, the use of the International Diabetes Federation (IDF) criteria has been suggested in children. Docosahexaenoic acid (DHA) has been associated with beneficial effects on health. The evidence about the relationship of DHA status in blood and components of the metabolic syndrome is unclear. This review discusses the possible association between DHA content in plasma and erythrocytes and components of the metabolic syndrome included in the IDF criteria (obesity, alteration of glucose metabolism, blood lipid profile, and blood pressure) and non-alcoholic fatty liver disease in obese children. The current evidence is inconsistent and no definitive conclusion can be drawn in the pediatric population. Well-designed longitudinal and powered trials need to clarify the possible association between blood DHA status and metabolic syndrome.

  12. Docosahexaenoic Acid Levels in Blood and Metabolic Syndrome in Obese Children: Is There a Link?

    Directory of Open Access Journals (Sweden)

    Carlotta Lassandro

    2015-08-01

    Full Text Available Prevalence of metabolic syndrome is increasing in the pediatric population. Considering the different existing criteria to define metabolic syndrome, the use of the International Diabetes Federation (IDF criteria has been suggested in children. Docosahexaenoic acid (DHA has been associated with beneficial effects on health. The evidence about the relationship of DHA status in blood and components of the metabolic syndrome is unclear. This review discusses the possible association between DHA content in plasma and erythrocytes and components of the metabolic syndrome included in the IDF criteria (obesity, alteration of glucose metabolism, blood lipid profile, and blood pressure and non-alcoholic fatty liver disease in obese children. The current evidence is inconsistent and no definitive conclusion can be drawn in the pediatric population. Well-designed longitudinal and powered trials need to clarify the possible association between blood DHA status and metabolic syndrome.

  13. Alpha-synuclein gene ablation increases docosahexaenoic acid incorporation and turnover in brain phospholipids

    DEFF Research Database (Denmark)

    Golovko, Mikhail Y; Rosenberger, Thad A; Feddersen, Søren

    2007-01-01

    Previously, we demonstrated that ablation of alpha-synuclein (Snca) reduces arachidonate (20:4n-6) turnover in brain phospholipids through modulation of an endoplasmic reticulum-localized acyl-CoA synthetase (Acsl). The effect of Snca ablation on docosahexaenoic acid (22:6n-3) metabolism is unknown...... and turnover in ethanolamine glycerophospholipid, phosphatidylserine, and phosphatidylinositol pools. Increased 22:6n-3-CoA mass was not the result of altered Acsl activity, which was unaffected by the absence of Snca. While Snca bound 22:6n-3, Kd = 1.0 +/- 0.5 micromol/L, it did not bind 22:6n-3-Co...

  14. Biotechnological Production of Docosahexaenoic Acid Using Aurantiochytrium limacinum: Carbon Sources Comparison And Growth Characterization

    Directory of Open Access Journals (Sweden)

    Sergi Abad

    2015-12-01

    Full Text Available Aurantiochytrium limacinum, a marine heterotrophic protist/microalga has shown interesting yields of docosahexaenoic acid (DHA when cultured with different carbon sources: glucose, pure and crude glycerol. A complete study in a lab-scale fermenter allowed for the characterization and comparison of the growth kinetic parameters corresponding to each carbon source. Artificial Marine Medium (AMM with glucose, pure and crude glycerol offered similar biomass yields. The net growth rates (0.10–0.12 h−1, biomass (0.7–0.8 g cells/g Substrate and product (0.14–0.15 g DHA/g cells yields, as well as DHA productivity were similar using the three carbon sources. Viable potential applications to valorize crude glycerol are envisioned to avoid an environmental problem due to the excess of byproduct.

  15. A novel therapeutic strategy for experimental stroke using docosahexaenoic acid complexed to human albumin

    Directory of Open Access Journals (Sweden)

    Belayev Ludmila

    2016-01-01

    Full Text Available Despite tremendous efforts in ischemic stroke research and significant improvements in patient care within the last decade, therapy is still insufficient. There is a compelling, urgent need for safe and effective neuroprotective strategies to limit brain injury, facilitate brain repair, and improve functional outcome. Recently, we reported that docosahexaenoic acid (DHA; 22:6, n-3 complexed to human albumin (DHA-Alb is highly neuroprotective after temporary middle cerebral artery occlusion (MCAo in young rats. This review highlights the potency of DHA-Alb therapy in permanent MCAo and aged rats and whether protection persists with chronic survival. We discovered that a novel therapy with DHA-Alb improved behavioral outcomes accompanied by attenuation of lesion volumes even when animals were allowed to survive three weeks after experimental stroke. This treatment might provide the basis for future therapeutics for patients suffering from ischemic stroke.

  16. Cancer Chemopreventive Ability of Conjugated Linolenic Acids

    Directory of Open Access Journals (Sweden)

    Kazuo Miyashita

    2011-11-01

    Full Text Available Conjugated fatty acids (CFA have received increased interest because of their beneficial effects on human health, including preventing cancer development. Conjugated linoleic acids (CLA are such CFA, and have been reviewed extensively for their multiple biological activities. In contrast to other types of CFAs including CLA that are found at low concentrations (less than 1% in natural products, conjugated linolenic acids (CLN are the only CFAs that occur in higher quantities in natural products. Some plant seeds contain a considerably high concentration of CLN (30 to 70 wt% lipid. Our research group has screened CLN from different plant seed oils to determine their cancer chemopreventive ability. This review describes the physiological functions of CLN isomers that occur in certain plant seeds. CLN are able to induce apoptosis through decrease of Bcl-2 protein in certain human cancer cell lines, increase expression of peroxisome proliferator-activated receptor (PPAR-γ, and up-regulate gene expression of p53. Findings in our preclinical animal studies have indicated that feeding with CLN resulted in inhibition of colorectal tumorigenesis through modulation of apoptosis and expression of PPARγ and p53. In this review, we summarize chemopreventive efficacy of CLN against cancer development, especially colorectal cancer.

  17. Inverse association between docosahexaenoic acid and mortality in patients on hemodialysis during over 10 years.

    Science.gov (United States)

    Terashima, Yoshihiro; Hamazaki, Kei; Itomura, Miho; Tomita, Shin; Kuroda, Masahiro; Hirata, Hitoshi; Hamazaki, Tomohito; Inadera, Hidekuni

    2014-07-01

    We have previously conducted a cohort study to investigate n-3 polyunsaturated fatty acids (PUFAs) in red blood cells (RBCs) and risk of all-cause mortality in hemodialysis (HD) patients over 5 years and found that n-3 PUFAs, especially docosahexaenoic acid (DHA), might be an independent predictor of all-cause mortality. In the present study, we extended the study for another 5 years to determine whether DHA levels in RBCs still predict the mortality of HD patients during a 10-year study period. The study cohort consisted of 176 patients (64.1 ± 12.0 [mean ± standard deviation] years of age, 96 men and 80 women) under HD treatment. The fatty acid composition of patients' RBCs was analyzed by gas chromatography. During the study period of 10 years, 97 deaths occurred. After adjustment for 10 confounding factors, the hazard ratio of all-cause mortality of the HD patients in the highest DHA tertile (>8.1%) was 0.52 (95% confidence interval 0.30-0.91) compared with those in the lowest DHA tertile (acid and docosapentaenoic acid (n-3) did not reveal any significant correlations. The level of DHA in RBCs could be an independent predictor of all-cause mortality in HD patients even during a long period of follow-up. © 2014 International Society for Hemodialysis.

  18. Dietary supplementation with docosahexaenoic acid (DHA) improves seminal antioxidant status and decreases sperm DNA fragmentation.

    Science.gov (United States)

    Martínez-Soto, Juan Carlos; Domingo, Joan Carles; Cordobilla, Begoña; Nicolás, María; Fernández, Laura; Albero, Pilar; Gadea, Joaquín; Landeras, José

    2016-12-01

    The purpose of this study was to evaluate the effect of docosahexaenoic acid (DHA) dietary supplementation on semen quality, fatty acid composition, antioxidant capacity, and DNA fragmentation. In this randomized, double blind, placebo-controlled, parallel-group study, 74 subjects were recruited and randomly assigned to either the placebo group (n=32) or to the DHA group (n=42) to consume three 500-mg capsules of oil per day over 10 weeks. The placebo group received 1,500 mg/day of sunflower oil and the DHA group 1,500 mg/day of DHA-enriched oil. Seminal parameters (semen volume, sperm concentration, motility, morphology, and vitality), total antioxidant capacity, deoxyribonucleic acid fragmentation, and lipid composition were evaluated prior to the treatment and after 10 weeks. Finally, 57 subjects were included in the study with 25 in the placebo group and 32 in the DHA group. No differences were found in traditional sperm parameters or lipid composition of the sperm membrane after treatment. However, an increase in DHA and Omega-3 fatty acid content in seminal plasma, an improvement in antioxidant status, and a reduction in the percentage of spermatozoa with deoxyribonucleic acid damage were observed in the DHA group after 10 weeks of treatment.

  19. Eicosapentaenoic and Docosahexaenoic Acid-Enriched High Fat Diet Delays Skeletal Muscle Degradation in Mice

    Directory of Open Access Journals (Sweden)

    Nikul K. Soni

    2016-09-01

    Full Text Available Low-grade chronic inflammatory conditions such as ageing, obesity and related metabolic disorders are associated with deterioration of skeletal muscle (SkM. Human studies have shown that marine fatty acids influence SkM function, though the underlying mechanisms of action are unknown. As a model of diet-induced obesity, we fed C57BL/6J mice either a high fat diet (HFD with purified marine fatty acids eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA (HFD-ED, a HFD with corn oil, or normal mouse chow for 8 weeks; and used transcriptomics to identify the molecular effects of EPA and DHA on SkM. Consumption of ED-enriched HFD modulated SkM metabolism through increased gene expression of mitochondrial β-oxidation and slow-fiber type genes compared with HFD-corn oil fed mice. Furthermore, HFD-ED intake increased nuclear localization of nuclear factor of activated T-cells (Nfatc4 protein, which controls fiber-type composition. This data suggests a role for EPA and DHA in mitigating some of the molecular responses due to a HFD in SkM. Overall, the results suggest that increased consumption of the marine fatty acids EPA and DHA may aid in the prevention of molecular processes that lead to muscle deterioration commonly associated with obesity-induced low-grade inflammation.

  20. Regulation of the Docosapentaenoic Acid/Docosahexaenoic Acid Ratio (DPA/DHA Ratio) in Schizochytrium limacinum B4D1.

    Science.gov (United States)

    Zhang, Ke; Li, Huidong; Chen, Wuxi; Zhao, Minli; Cui, Haiyang; Min, Qingsong; Wang, Haijun; Chen, Shulin; Li, Demao

    2017-05-01

    Docosapentaenoic acid/docosahexaenoic acid ratio (DPA/DHA ratio) in Schizochytrium was relatively stable. But ideally the ratio of DPA/DHA will vary according to the desired end use. This study reports several ways of modulating the DPA/DHA ratio. Incubation times changed the DPA/DHA ratio, and changes in this ratio were associated with the variations in the saturated fatty acid (SFAs) content. Propionic acid sharply increased the SFAs content in lipids, dramatically decreased the even-chain SFAs content, and reduced the DPA/DHA ratio. Pentanoic acid (C5:0) and heptanoic acid (C7:0) had similar effects as propionic acid, whereas butyric acid (C4:0), hexanoic acid (C6:0), and octanoic acid (C8:0) did not change the fatty acid profile and the DPA/DHA ratio. Transcription analyses show that β-oxidation might be responsible for this phenomenon. Iodoacetamide upregulated polyunsaturated fatty acid (PUFA) synthase genes, reduced the DHA content, and improved the DPA content, causing the DPA/DHA ratio to increase. These results present new insights into the regulation of the DPA/DHA ratio.

  1. N-3 fatty acids reduced trans fatty acids retention and increased docosahexaenoic acid levels in the brain.

    Science.gov (United States)

    Lavandera, Jimena Verónica; Saín, Juliana; Fariña, Ana Clara; Bernal, Claudio Adrián; González, Marcela Aída

    2017-09-01

    The levels of docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) are critical for the normal structure and function of the brain. Trans fatty acids (TFA) and the source of the dietary fatty acids (FA) interfere with long-chain polyunsaturated fatty acids (LC-PUFA) biosynthesis. The aim of this study was to investigate the effect of TFA supplementation in diets containing different proportions of n-9, n-6, and n-3 FA on the brain FA profile, including the retention of TFA, LC-PUFA levels, and n-6/n-3 PUFA ratios. These parameters were also investigated in the liver, considering that LC-PUFA are mainly bioconverted from their dietary precursors in this tissue and transported by serum to the brain. Also, stearoyl-CoA desaturase-1 (SCD1) and sterol regulatory element-binding protein-1c (SREBP-1c) gene expressions were evaluated. Male CF1 mice were fed (16 weeks) diets containing different oils (olive, corn, and rapeseed) with distinct proportions of n-9, n-6, and n-3 FA (55.2/17.2/0.7, 32.0/51.3/0.9, and 61.1/18.4/8.6), respectively, substituted or not with 0.75% of TFA. FA composition of the brain, liver, and serum was assessed by gas chromatography. TFA were incorporated into, and therefore retained in the brain, liver, and serum. However, the magnitude of retention was dependent on the tissue and type of isomer. In the brain, total TFA retention was lower than 1% in all diets. Dietary n-3 PUFA decreased TFA retention and increased DHA accretion in the brain. The results underscore the importance of the type of dietary FA on the retention of TFA in the brain and also on the changes of the FA profile.

  2. Mechanisms regulating brain docosahexaenoic acid uptake: what is the recent evidence?

    Science.gov (United States)

    Chouinard-Watkins, Raphaël; Lacombe, R J Scott; Bazinet, Richard P

    2018-03-01

    To summarize recent advances pertaining to the mechanisms regulating brain docosahexaenoic acid (DHA) uptake. DHA is an omega-3 polyunsaturated fatty acid highly enriched in neuronal membranes and it is implicated in several important neurological processes. However, DHA synthesis is extremely limited within the brain. There are two main plasma pools that supply the brain with DHA: the nonesterified pool and the lysophosphatidylcholine (lysoPtdCho) pool. Quantitatively, plasma nonesterified-DHA (NE-DHA) is the main contributor to brain DHA. Fatty acid transport protein 1 (FATP1) in addition to fatty acid-binding protein 5 (FABP5) are key players that regulate brain uptake of NE-DHA. However, the plasma half-life of lysoPtdCho-DHA and its brain partition coefficient are higher than those of NE-DHA after intravenous administration. The mechanisms regulating brain DHA uptake are more complicated than once believed, but recent advances provide some clarity notably by suggesting that FATP1 and FABP5 are key contributors to cellular uptake of DHA at the blood-brain barrier. Elucidating how DHA enters the brain is important as we might be able to identify methods to better deliver DHA to the brain as a potential therapeutic.

  3. Docosahexaenoic acid in the goat kid diet: effects on immune system and meat quality.

    Science.gov (United States)

    Moreno-Indias, I; Morales-delaNuez, A; Hernández-Castellano, L E; Sánchez-Macías, D; Capote, J; Castro, N; Argüello, A

    2012-11-01

    The effect of dietary docosahexaenoic acid (C22:6n3; DHA) supplementation on meat quality and immunity in goat (Capra hircus) kids was examined. Goat kids (n = 30) were fed 1 of 3 experimental diets: goat milk (GM), cow (Bos taurus) milk (CM), and CM supplemented with DHA (CM-DHA). Animals were fed ad libitum twice daily and weighed twice each week. Blood samples were collected by jugular venipuncture daily during the first 10 d of life and were subsequently collected every 5 d until slaughter at a BW of 8 kg. Carcass size (linear measurements) and weight, as well as meat pH, color, tenderness, and chemical composition were determined. Fatty acid profiles of intramuscular, peri-renal, pelvic, subcutaneous, and intermuscular fats were analyzed. Blood IgG and IgM concentrations, complement system activity (classical and alternative pathways), and chitotriosidase activity were recorded. Results indicated that the diet containing DHA did not affect (P > 0.05) carcass linear measurements, meat quality characteristics, or proximate composition of the meat. However, C22:6n3 fatty acid levels, mainly in intramuscular fat, were enriched (P 0.05) in immune function were observed among groups. In conclusion, powdered whole CM is an effective option for feeding goat kids, and the inclusion of DHA to CM increases the quantity of this fatty acid in the meat.

  4. IMAGING BRAIN SIGNAL TRANSDUCTION AND METABOLISM VIA ARACHIDONIC AND DOCOSAHEXAENOIC ACID IN ANIMALS AND HUMANS

    Science.gov (United States)

    Basselin, Mireille; Ramadan, Epolia; Rapoport, Stanley I.

    2012-01-01

    The polyunsaturated fatty acids (PUFAs), arachidonic acid (AA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3), important second messengers in brain, are released from membrane phospholipid following receptor-mediated activation of specific phospholipase A2 (PLA2) enzymes. We developed an in vivo method in rodents using quantitative autoradiography to image PUFA incorporation into brain from plasma, and showed that their incorporation rates equal their rates of metabolic consumption by brain. Thus, quantitative imaging of unesterified plasma AA or DHA incorporation into brain can be used as a biomarker of brain PUFA metabolism and neurotransmission. We have employed our method to image and quantify effects of mood stabilizers on brain AA/DHA incorporation during neurotransmission by muscarinic M1,3,5, serotonergic 5-HT2A/2C, dopaminergic D2-like (D2, D3, D4) or glutamatergic N-methyl-D-aspartic acid (NMDA) receptors, and effects of inhibition of acetylcholinesterase, of selective serotonin and dopamine reuptake transporter inhibitors, of neuroinflammation (HIV-1 and lipopolysaccharide) and excitotoxicity, and in genetically modified rodents. The method has been extended for the use with positron emission tomography (PET), and can be employed to determine how human brain AA/DHA signaling and consumption are influenced by diet, aging, disease and genetics. PMID:22178644

  5. Impact of Docosahexaenoic Acid on Gene Expression during Osteoclastogenesis in Vitro—A Comprehensive Analysis

    Directory of Open Access Journals (Sweden)

    Ikuo Morita

    2013-08-01

    Full Text Available Polyunsaturated fatty acids (PUFAs, especially n-3 polyunsaturated fatty acids, docosahexaenoic acid (DHA and eicosapentaenoic acid (EPA, are known to protect against inflammation-induced bone loss in chronic inflammatory diseases, such as rheumatoid arthritis, periodontitis and osteoporosis. We previously reported that DHA, not EPA, inhibited osteoclastogenesis induced by the receptor activator of nuclear factor-κB ligand (sRANKL in vitro. In this study, we performed gene expression analysis using microarrays to identify genes affected by the DHA treatment during osteoclastogenesis. DHA strongly inhibited osteoclastogenesis at the late stage. Among the genes upregulated by the sRANKL treatment, 4779 genes were downregulated by DHA and upregulated by the EPA treatment. Gene ontology analysis identified sets of genes related to cell motility, cell adhesion, cell-cell signaling and cell morphogenesis. Quantitative PCR analysis confirmed that DC-STAMP, an essential gene for the cell fusion process in osteoclastogenesis, and other osteoclast-related genes, such as Siglec-15, Tspan7 and Mst1r, were inhibited by DHA.

  6. Docosahexaenoic Acid (DHA: An Ancient Nutrient for the Modern Human Brain

    Directory of Open Access Journals (Sweden)

    Joanne Bradbury

    2011-05-01

    Full Text Available Modern humans have evolved with a staple source of preformed docosahexaenoic acid (DHA in the diet. An important turning point in human evolution was the discovery of high-quality, easily digested nutrients from coastal seafood and inland freshwater sources. Multi-generational exploitation of seafood by shore-based dwellers coincided with the rapid expansion of grey matter in the cerebral cortex, which characterizes the modern human brain. The DHA molecule has unique structural properties that appear to provide optimal conditions for a wide range of cell membrane functions. This has particular implications for grey matter, which is membrane-rich tissue. An important metabolic role for DHA has recently been identified as the precursor for resolvins and protectins. The rudimentary source of DHA is marine algae; therefore it is found concentrated in fish and marine oils. Unlike the photosynthetic cells in algae and higher plants, mammalian cells lack the specific enzymes required for the de novo synthesis of alpha-linolenic acid (ALA, the precursor for all omega-3 fatty acid syntheses. Endogenous synthesis of DHA from ALA in humans is much lower and more limited than previously assumed. The excessive consumption of omega-6 fatty acids in the modern Western diet further displaces DHA from membrane phospholipids. An emerging body of research is exploring a unique role for DHA in neurodevelopment and the prevention of neuropsychiatric and neurodegenerative disorders. DHA is increasingly being added back into the food supply as fish oil or algal oil supplementation.

  7. Docosahexaenoic acid is an independent predictor of all-cause mortality in hemodialysis patients.

    Science.gov (United States)

    Hamazaki, Kei; Terashima, Yoshihiro; Itomura, Miho; Sawazaki, Shigeki; Inagaki, Hitoshi; Kuroda, Masahiro; Tomita, Shin; Hirata, Hitoshi; Inadera, Hidekuni; Hamazaki, Tomohito

    2011-01-01

    Dietary n-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA) and eicosapentaenoic acid have been shown to reduce cardiovascular mortality. Patients on hemodialysis (HD) have a very high mortality from cardiovascular disease. Fish consumption reduces all-cause mortality in patients on HD. Moreover, n-3 PUFAs, especially DHA levels in red blood cells (RBCs), are associated with arteriosclerosis in patients on HD. The aim of this study was to determine whether DHA levels in RBCs predict the mortality of patients on HD in a prospective cohort study. A cohort of 176 patients (64.1 ± 12.0 (mean ± SD) years of age, 96 men and 80 women) under HD treatment was studied. The fatty acid composition of their RBCs was analyzed by gas chromatography. During the study period of 5 years, 54 deaths occurred. After adjustment for 10 confounding factors, the Cox hazard ratio of all-cause mortality of the patients on HD in the highest DHA tertile (>8.1%, 15 deaths) was 0.43 (95% CI 0.21-0.88) compared with those patients in the lowest DHA tertile (HD. Copyright © 2010 S. Karger AG, Basel.

  8. The Relationship of Docosahexaenoic Acid (DHA) with Learning and Behavior in Healthy Children: A Review

    Science.gov (United States)

    Kuratko, Connye N.; Barrett, Erin Cernkovich; Nelson, Edward B.; Norman, Salem

    2013-01-01

    Childhood is a period of brain growth and maturation. The long chain omega-3 fatty acid, docosahexaenoic acid (DHA), is a major lipid in the brain recognized as essential for normal brain function. In animals, low brain DHA results in impaired learning and behavior. In infants, DHA is important for optimal visual and cognitive development. The usual intake of DHA among toddlers and children is low and some studies show improvements in cognition and behavior as the result of supplementation with polyunsaturated fatty acids including DHA. The purpose of this review was to identify and evaluate current knowledge regarding the relationship of DHA with measures of learning and behavior in healthy school-age children. A systematic search of the literature identified 15 relevant publications for review. The search found studies which were diverse in purpose and design and without consistent conclusions regarding the treatment effect of DHA intake or biomarker status on specific cognitive tests. However, studies of brain activity reported benefits of DHA supplementation and over half of the studies reported a favorable role for DHA or long chain omega-3 fatty acids in at least one area of cognition or behavior. Studies also suggested an important role for DHA in school performance. PMID:23877090

  9. Docosahexaenoic acid (DHA): an ancient nutrient for the modern human brain.

    Science.gov (United States)

    Bradbury, Joanne

    2011-05-01

    Modern humans have evolved with a staple source of preformed docosahexaenoic acid (DHA) in the diet. An important turning point in human evolution was the discovery of high-quality, easily digested nutrients from coastal seafood and inland freshwater sources. Multi-generational exploitation of seafood by shore-based dwellers coincided with the rapid expansion of grey matter in the cerebral cortex, which characterizes the modern human brain. The DHA molecule has unique structural properties that appear to provide optimal conditions for a wide range of cell membrane functions. This has particular implications for grey matter, which is membrane-rich tissue. An important metabolic role for DHA has recently been identified as the precursor for resolvins and protectins. The rudimentary source of DHA is marine algae; therefore it is found concentrated in fish and marine oils. Unlike the photosynthetic cells in algae and higher plants, mammalian cells lack the specific enzymes required for the de novo synthesis of alpha-linolenic acid (ALA), the precursor for all omega-3 fatty acid syntheses. Endogenous synthesis of DHA from ALA in humans is much lower and more limited than previously assumed. The excessive consumption of omega-6 fatty acids in the modern Western diet further displaces DHA from membrane phospholipids. An emerging body of research is exploring a unique role for DHA in neurodevelopment and the prevention of neuropsychiatric and neurodegenerative disorders. DHA is increasingly being added back into the food supply as fish oil or algal oil supplementation.

  10. Thraustochytrids as production organisms for docosahexaenoic acid (DHA), squalene, and carotenoids.

    Science.gov (United States)

    Aasen, Inga Marie; Ertesvåg, Helga; Heggeset, Tonje Marita Bjerkan; Liu, Bin; Brautaset, Trygve; Vadstein, Olav; Ellingsen, Trond E

    2016-05-01

    Thraustochytrids have been applied for industrial production of the omega-3 fatty acid docosahexaenoic (DHA) since the 1990s. During more than 20 years of research on this group of marine, heterotrophic microorganisms, considerable increases in DHA productivities have been obtained by process and medium optimization. Strains of thraustochytrids also produce high levels of squalene and carotenoids, two other commercially interesting compounds with a rapidly growing market potential, but where yet few studies on process optimization have been reported. Thraustochytrids use two pathways for fatty acid synthesis. The saturated fatty acids are produced by the standard fatty acid synthesis, while DHA is synthesized by a polyketide synthase. However, fundamental knowledge about the relationship between the two pathways is still lacking. In the present review, we extract main findings from the high number of reports on process optimization for DHA production and interpret these in the light of the current knowledge of DHA synthesis in thraustochytrids and lipid accumulation in oleaginous microorganisms in general. We also summarize published reports on squalene and carotenoid production and review the current status on strain improvement, which has been hampered by the yet very few published genome sequences and the lack of tools for gene transfer to the organisms. As more sequences now are becoming available, targets for strain improvement can be identified and open for a system-level metabolic engineering for improved productivities.

  11. The Relationship of Docosahexaenoic Acid (DHA with Learning and Behavior in Healthy Children: A Review

    Directory of Open Access Journals (Sweden)

    Norman Salem

    2013-07-01

    Full Text Available Childhood is a period of brain growth and maturation. The long chain omega-3 fatty acid, docosahexaenoic acid (DHA, is a major lipid in the brain recognized as essential for normal brain function. In animals, low brain DHA results in impaired learning and behavior. In infants, DHA is important for optimal visual and cognitive development. The usual intake of DHA among toddlers and children is low and some studies show improvements in cognition and behavior as the result of supplementation with polyunsaturated fatty acids including DHA. The purpose of this review was to identify and evaluate current knowledge regarding the relationship of DHA with measures of learning and behavior in healthy school-age children. A systematic search of the literature identified 15 relevant publications for review. The search found studies which were diverse in purpose and design and without consistent conclusions regarding the treatment effect of DHA intake or biomarker status on specific cognitive tests. However, studies of brain activity reported benefits of DHA supplementation and over half of the studies reported a favorable role for DHA or long chain omega-3 fatty acids in at least one area of cognition or behavior. Studies also suggested an important role for DHA in school performance.

  12. Alcohol abuse and docosahexaenoic acid: Effects on cerebral circulation and neurosurvival

    Directory of Open Access Journals (Sweden)

    Michael A Collins

    2015-01-01

    Full Text Available Alcohol abuse and alcoholism are major and yet surprisingly unacknowledged worldwide causes of brain damage, cognitive impairment, and dementia. Chronic abuse of alcohol is likely to elicit significant changes in essential polyenoic fatty acids and the membrane phospholipids (PLs that covalently contain them in brain membranes. Among the fatty acids of the omega-3 polyenoic class, docosahexaenoic acid (DHA, which is relatively concentrated in mammalian brain, has proven particularly important for proper brain development as well as neurosurvival and protection. DHA losses in brains of chronic alcohol-treated animals may contribute to alcohol′s neuroinflammatory and neuropathological sequelae; indeed, DHA supplementation has beneficial effects, including the possibility that its documented augmenting effects on cerebral circulation could be important. The neurochemical mechanisms by which DHA exerts its effects encompass several signaling routes involving both the membrane PLs in which DHA is esterified as well as unique neuroactive metabolites of the free fatty acid itself. In view of indications that brain DHA deficits are a deleterious outcome of human alcoholism, increasing brain DHA via supplementation during detoxification of alcoholics could potentially fortify against dependence-related neuroinjury.

  13. High levels of retinal membrane docosahexaenoic acid increase susceptibility to stress-induced degenerations⃞

    Science.gov (United States)

    Tanito, Masaki; Brush, Richard S.; Elliott, Michael H.; Wicker, Lea D.; Henry, Kimberly R.; Anderson, Robert E.

    2009-01-01

    The fat-1 gene cloned from C. elegans encodes an n-3 fatty acid desaturase that converts n-6 to n-3 PUFA. Mice carrying the fat-1 transgene and wild-type controls were fed an n-3-deficient/n-6-enriched diet [fat-1- safflower oil (SFO) and wt-SFO, respectively]. Fatty acid profiles of rod outer segments (ROS), cerebellum, plasma, and liver demonstrated significantly lower n-6/n-3 ratios and higher docosahexaenoic acid (DHA) levels in fat-1-SFO compared with wt-SFO. When mice were exposed to light stress: 1) the outer nuclear layer (ONL) thickness was reduced; 2) amplitudes of the electroretinogram (ERG) were lower; 3) the number of apoptotic photoreceptor cells was greater; and 4) modification of retinal proteins by 4-hydroxyhexenal (4-HHE), an end-product of n-3 PUFA oxidation was increased in both fat-1-SFO and wt mice fed a regular lab chow diet compared with wt-SFO. The results indicate a positive correlation between the level of DHA, the degree of n-3 PUFA lipid peroxidation, and the vulnerability of the retina to photooxidative stress. In mice not exposed to intense light, the reduction in DHA resulted in reduced efficacy in phototransduction gain steps, while no differences in the retinal morphology or retinal biochemistry. These results highlight the dual roles of DHA in cellular physiology and pathology. PMID:19023138

  14. The pleiotropic effects of omega-3 docosahexaenoic acid on the hallmarks of Alzheimer's disease.

    Science.gov (United States)

    Belkouch, Mounir; Hachem, Mayssa; Elgot, Abdeljalil; Lo Van, Amanda; Picq, Madeleine; Guichardant, Michel; Lagarde, Michel; Bernoud-Hubac, Nathalie

    2016-12-01

    Among omega-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA, 22:6n-3) is important for adequate brain development and cognition. DHA is highly concentrated in the brain and plays an essential role in brain functioning. DHA, one of the major constituents in fish fats, readily crosses the blood-brain barrier from blood to the brain. Its critical role was further supported by its reduced levels in the brain of Alzheimer's disease (AD) patients. This agrees with a potential role of DHA in memory, learning and cognitive processes. Since there is yet no cure for dementia such as AD, there is growing interest in the role of DHA-supplemented diet in the prevention of AD pathogenesis. Accordingly, animal, epidemiological, preclinical and clinical studies indicated that DHA has neuroprotective effects in a number of neurodegenerative conditions including AD. The beneficial effects of this key omega-3 fatty acid supplementation may depend on the stage of disease progression, other dietary mediators and the apolipoprotein ApoE genotype. Herein, our review investigates, from animal and cell culture studies, the molecular mechanisms involved in the neuroprotective potential of DHA with emphasis on AD. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Low levels of docosahexaenoic acid identified in acute coronary syndrome patients with depression.

    Science.gov (United States)

    Parker, Gordon B; Heruc, Gabriella A; Hilton, Therese M; Olley, Amanda; Brotchie, Heather; Hadzi-Pavlovic, Dusan; Friend, Cheryl; Walsh, Warren F; Stocker, Roland

    2006-03-30

    As deficiencies in n-3 PUFAs have been linked separately to depression and to cardiovascular disease, they could act as a higher order variable contributing to the established link between depression and cardiovascular disease. We therefore examine the relationship between depression and omega-3 polyunsaturated fatty acids (n-3 PUFA), including total n-3 PUFA, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), in patients with acute coronary syndrome (ACS). Plasma phospholipid levels of n-3 PUFA were measured in 100 patients hospitalized with ACS. Current major depressive episode was assessed by the Composite International Diagnostic Interview (CIDI). Depression severity was assessed by the 18-item Depression in the Medically Ill (DMI-18) measure. Patients clinically diagnosed with current depression had significantly lower mean total n-3 PUFA and DHA levels. Higher DMI-18 depression severity scores were significantly associated with lower DHA levels, with similar but non-significant trends observed for EPA and total n-3 PUFA levels. The finding that low DHA levels were associated with depression variables in ACS patients may explain links demonstrated between cardiovascular health and depression, and may have prophylactic and treatment implications.

  16. Enhancement of docosahexaenoic acid (DHA) production from Schizochytrium sp. S31 using different growth medium conditions.

    Science.gov (United States)

    Sahin, Deniz; Tas, Ezgi; Altindag, Ulkü Hüma

    2018-01-24

    Schizochytrium species is one of the most studied microalgae for production of docosahexaenoic acid (DHA) which is an omega-3 fatty acid with positive effects for human health. However, high cost and low yield in production phase makes optimization of cultivation process inevitable. We focus on the optimization of DHA production using Schizochytrium sp. using different media supplements; glucose, fructose and glycerol as carbon variants, proteose peptone and tryptone as nitrogen variants. The highest biomass (5.61 g/L) and total fatty acid yield (1.74 g/L) were obtained in proteose peptone medium which was used as the alternative nitrogen source instead of yeast extract. The highest DHA yield (0.40 g/L) was achieved with glycerol as the carbon source although it had the second lowest biomass production after ethanol containing medium. Ethanol, as an alternative carbon source and a precursor for acetyl-CoA, increased DHA percentage in total lipid content from 29.94 to 40.04% but decreasing the biomass drastically. Considering different carbon and nitrogen sources during cultivation of Schizochytrium sp. will improve DHA production. Combination of proteose peptone and glycerol as nitrogen and carbon sources, respectively, and addition of ethanol with a proper timing will be useful to have higher DHA yield.

  17. Sources and Bioactive Properties of Conjugated Dietary Fatty Acids.

    Science.gov (United States)

    Hennessy, Alan A; Ross, Paul R; Fitzgerald, Gerald F; Stanton, Catherine

    2016-04-01

    The group of conjugated fatty acids known as conjugated linoleic acid (CLA) isomers have been extensively studied with regard to their bioactive potential in treating some of the most prominent human health malignancies. However, CLA isomers are not the only group of potentially bioactive conjugated fatty acids currently undergoing study. In this regard, isomers of conjugated α-linolenic acid, conjugated nonadecadienoic acid and conjugated eicosapentaenoic acid, to name but a few, have undergone experimental assessment. These studies have indicated many of these conjugated fatty acid isomers commonly possess anti-carcinogenic, anti-adipogenic, anti-inflammatory and immune modulating properties, a number of which will be discussed in this review. The mechanisms through which these bioactivities are mediated have not yet been fully elucidated. However, existing evidence indicates that these fatty acids may play a role in modulating the expression of several oncogenes, cell cycle regulators, and genes associated with energy metabolism. Despite such bioactive potential, interest in these conjugated fatty acids has remained low relative to the CLA isomers. This may be partly attributed to the relatively recent emergence of these fatty acids as bioactives, but also due to a lack of awareness regarding sources from which they can be produced. In this review, we will also highlight the common sources of these conjugated fatty acids, including plants, algae, microbes and chemosynthesis.

  18. Blood docosahexaenoic acid and eicosapentaenoic acid in vegans: Associations with age and gender and effects of an algal-derived omega-3 fatty acid supplement.

    Science.gov (United States)

    Sarter, Barbara; Kelsey, Kristine S; Schwartz, Todd A; Harris, William S

    2015-04-01

    Several studies have demonstrated that vegetarians and vegans have much lower plasma concentrations of omega-3 fatty acids (i.e., docosahexaenoic and eicosapentaenoic acids) when compared to those who eat fish. The purposes of this study were 1) to define the age and/or sex-specific docosahexaenoic plus eicosapentaenoic acids levels in red blood cell membranes (expressed as a percent of total fatty acids; hereafter the omega-3 index) in long-term vegans, and 2) to determine the effects of a vegetarian omega-3 supplement (254 mg docosahexaenoic plus eicosapentaenoic acids/day for 4 months) on the omega-3 index. A sample (n = 165) of vegans was recruited, and their omega-3 index was determined using a dried blood spot methodology. A subset of 46 subjects with a baseline omega-3 index of vegan cohort, the index was significantly higher in females than males (3.9 ± 1.0% vs. 3.5 ± 1.0%; p = 0.026) and was directly related to age (p for trend = 0.009). The omega-3 index increased from 3.1 ± 0.6% to 4.8 ± 0.8% (p = 0.009) in the supplementation study. We conclude that vegans have low baseline omega-3 levels, but not lower than omnivores who also consume very little docosahexaenoic and eicosapentaenoic acids. The vegans responded robustly to a relatively low dose of a vegetarian omega-3 supplement. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Should there be a target level of docosahexaenoic acid in breast milk?

    Science.gov (United States)

    Jackson, Kristina Harris; Harris, William S

    2016-03-01

    This article examines the evidence for and against establishing a target level of docosahexaenoic acid (DHA) in breast milk. Two target levels for milk DHA have been recently proposed. One (∼0.3% of milk fatty acids) was based on milk DHA levels achieved in women consuming the amount of DHA recommended by the American Academy of Pediatrics for pregnant and lactating women (at least 200 mg DHA/day). Another (∼1.0%) was based on biomarker studies of populations with differing lifelong intakes of fish. Populations or research cohorts with milk DHA levels of 1.0% are associated with intakes that allow both the mother and infant to maintain relatively high DHA levels throughout lactation. Lower milk DHA levels may signal suboptimal maternal stores and possibly suboptimal infant intakes. Based on the current data, a reasonable milk DHA target appears to be approximately 0.3%, which is about the worldwide average. Although this may not be the 'optimal' level (which remains to be defined), it is clearly an improvement over the currently low milk DHA levels (∼0.2%) seen in many Western populations.

  20. Adjunctive low-dose docosahexaenoic acid (DHA) for major depression: An open-label pilot trial.

    Science.gov (United States)

    Smith, Deidre J; Sarris, Jerome; Dowling, Nathan; O'Connor, Manjula; Ng, Chee H

    2018-04-01

    Whilst the majority of evidence supports the adjunctive use of eicosapentaenoic acid (EPA) in improving mood, to date no study exists using low-dose docosahexaenoic acid (DHA) alone as an adjunctive treatment in patients with mild to moderate major depressive disorder (MDD). A naturalistic 8-week open-label pilot trial of low-dose DHA, (260 mg or 520 mg/day) in 28 patients with MDD who were non-responsive to medication or psychotherapy, with a Hamilton Depression Rating Scale (HAM-D) score of greater than 17, was conducted. Primary outcomes of depression, clinical severity, and daytime sleepiness were measured. After 8 weeks, 54% of patients had a ≥50% reduction on the HAM-D, and 45% were in remission (HAM-D ≤ 7). The eta-squared statistic (0.59) indicated a large effect size for the reduction of depression (equivalent to Cohen's d of 2.4). However confidence in this effect size is tempered due to the lack of a placebo. The mean score for the Clinical Global Impression Severity Scale was significantly improved by 1.28 points (P depression.

  1. Plasma non-esterified docosahexaenoic acid is the major pool supplying the brain.

    Science.gov (United States)

    Chen, Chuck T; Kitson, Alex P; Hopperton, Kathryn E; Domenichiello, Anthony F; Trépanier, Marc-Olivier; Lin, Lauren E; Ermini, Leonardo; Post, Martin; Thies, Frank; Bazinet, Richard P

    2015-10-29

    Despite being critical for normal brain function, the pools that supply docosahexaenoic acid (DHA) to the brain are not agreed upon. Using multiple kinetic models in free-living adult rats, we first demonstrate that DHA uptake from the plasma non-esterified fatty acid (NEFA) pool predicts brain uptake of DHA upon oral administration, which enters the plasma NEFA pool as well as multiple plasma esterified pools. The rate of DHA loss by the brain is similar to the uptake from the plasma NEFA pool. Furthermore, upon acute iv administration, although more radiolabeled lysophosphatidylcholine (LPC)-DHA enters the brain than NEFA-DHA, this is due to the longer plasma half-life and exposure to the brain. Direct comparison of the uptake rate of LPC-DHA and NEFA-DHA demonstrates that uptake of NEFA-DHA into the brain is 10-fold greater than LPC-DHA. In conclusion, plasma NEFA-DHA is the major plasma pool supplying the brain.

  2. Response surface optimization of culture medium for enhanced docosahexaenoic acid production by a Malaysian thraustochytrid.

    Science.gov (United States)

    Manikan, Vidyah; Kalil, Mohd Sahaid; Hamid, Aidil Abdul

    2015-02-27

    Docosahexaenoic acid (DHA, C22:6n-3) plays a vital role in the enhancement of human health, particularly for cognitive, neurological, and visual functions. Marine microalgae, such as members of the genus Aurantiochytrium, are rich in DHA and represent a promising source of omega-3 fatty acids. In this study, levels of glucose, yeast extract, sodium glutamate and sea salt were optimized for enhanced lipid and DHA production by a Malaysian isolate of thraustochytrid, Aurantiochytrium sp. SW1, using response surface methodology (RSM). The optimized medium contained 60 g/L glucose, 2 g/L yeast extract, 24 g/L sodium glutamate and 6 g/L sea salt. This combination produced 17.8 g/L biomass containing 53.9% lipid (9.6 g/L) which contained 44.07% DHA (4.23 g/L). The optimized medium was used in a scale-up run, where a 5 L bench-top bioreactor was employed to verify the applicability of the medium at larger scale. This produced 24.46 g/L biomass containing 38.43% lipid (9.4 g/L), of which 47.87% was DHA (4.5 g/L). The total amount of DHA produced was 25% higher than that produced in the original medium prior to optimization. This result suggests that Aurantiochytrium sp. SW1 could be developed for industrial application as a commercial DHA-producing microorganism.

  3. Effect of Docosahexaenoic Acid on Apoptosis and Proliferation in the Placenta: Preliminary Report

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    Ewa Wietrak

    2015-01-01

    Full Text Available Introduction. Observational studies confirm a higher incidence of preeclampsia in patients with low erythrocyte concentrations of omega-3 fatty acids. Observations point to an association of disorders of pregnancy, such as intrauterine growth restriction (IUGR and preeclampsia, with excessive apoptosis. One potential mechanism of action of docosahexaenoic acid (DHA promoting a reduction in the risk of pathological pregnancy may be by influencing these processes in the placenta. Materials and Methods. We investigated 28 pregnant women supplemented with a fish oil product containing 300 mg DHA starting from pregnancy week 20 until delivery (DHA group. The control group consisted of 50 women who did not receive such supplementation (control group. We determined the expression of Ki-67 and p21 as markers of proliferation and caspase 3 activity as a marker of apoptosis and DHA levels in umbilical cord blood. Results. Caspase 3 activity was significantly lower in the DHA group in comparison to the control group. Umbilical cord blood DHA concentration was higher in the DHA group. The expression of the proteins p21 and Ki-67 did not differ significantly between the groups. Conclusions. We observed an association between DHA supplementation and inhibition of placental apoptosis. We did not find an association between DHA and proliferation process in the placenta.

  4. A Critical Review on the Effect of Docosahexaenoic Acid (DHA) on Cancer Cell Cycle Progression.

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    Newell, Marnie; Baker, Kristi; Postovit, Lynne M; Field, Catherine J

    2017-08-17

    Globally, there were 14.1 million new cancer diagnoses and 8.2 million cancer deaths in 2012. For many cancers, conventional therapies are limited in their successes and an improved understanding of disease progression is needed in conjunction with exploration of alternative therapies. The long chain polyunsaturated fatty acid, docosahexaenoic acid (DHA), has been shown to enhance many cellular responses that reduce cancer cell viability and decrease proliferation both in vitro and in vivo. A small number of studies suggest that DHA improves chemotherapy outcomes in cancer patients. It is readily incorporated into cancer cell membranes and, as a result there has been considerable research regarding cell membrane initiated events. For example, DHA has been shown to mediate the induction of apoptosis/reduction of proliferation in vitro and in vivo. However, there is limited research into the effect of DHA on cell cycle regulation in cancer cells and the mechanism(s) by which DHA acts are not fully understood. The purpose of the current review is to provide a critical examination of the literature investigating the ability of DHA to stall progression during different cell cycle phases in cancer cells, as well as the consequences that these changes may have on tumour growth, independently and in conjunction with chemotherapy.

  5. Efficient production of triacylglycerols rich in docosahexaenoic acid (DHA) by osmo-heterotrophic marine protists.

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    Liu, Ying; Tang, Jie; Li, Jingjing; Daroch, Maurycy; Cheng, Jay J

    2014-12-01

    Thraustochytrids have recently emerged as a promising source for docosahexaenoic acid (DHA) production due to their high growth rate and oil content. In this study, two thraustochytrid isolates, Aurantiochytrium sp. PKU#SW7 and Thraustochytriidae sp. PKU#Mn16 were used for DHA production. Following growth parameters were optimized to maximize DHA production: temperature, pH, salinity, and glucose concentration. Both isolates achieved the highest DHA yield at the cultivation temperature of 28 °C, pH 6, 100 % seawater, and 2 % glucose. A DHA yield of 1.395 g/l and 1.426 g/l was achieved under the optimized culture conditions. Further investigation revealed that both isolates possess simple fatty acids profiles with palmitic acid and DHA as their dominant constituents, accounting for ∼79 % of total fatty acids. To date, very few studies have focused on the DHA distribution in various lipid fractions which is an important factor for identifying strains with a potential for industrial DHA production. In the present study, the lipids profiles of each strain both revealed that the majority of DHA was distributed in neutral lipids (NLs), and the DHA distribution in NLs of PKU#SW7 was exclusively in the form of triacylglycerols (TAGs) which suggest that PKU#SW7 could be utilized as an alternative source of DHA for dietary supplements. The fermentation process established for both strains also indicating that Aurantiochytrium sp. PKU#SW7 was more suitable for cultivation in fermenter. In addition, the high percentage of saturated fatty acids produced by the two thraustochytrids indicates their potential application in biodiesel production. Overall, our findings suggest that two thraustochytrid isolates are suitable candidates for biotechnological applications.

  6. Conjugated linoleic acid in ewe milk fat.

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    Luna, Pilar; Fontecha, Javier; Juárez, Manuela; de la Fuente, Miguel Angel

    2005-11-01

    Ewe milk fat from five different herds was studied to determine the content of conjugated linoleic acid (CLA) isomers. Research was carried out by combining gas chromatography-mass spectrometry (GC-MS) of fatty acid methyl esters (FAME) and 4,4-dimethyloxazolyne derivatives (DMOX) with silver ion-high performance liquid chromatography (Ag+-HPLC). Reconstructed mass spectral profiles of CLA characteristic ions from DMOX were used to identify positional isomers and Ag+-HPLC to quantify them. Total CLA content varied from 0.57 to 0.97 g/100 g of total fatty acids. FAME and DMOX were separated into a complex mixture of minor isomers and major rumenic acid (9-cis 11-trans C18:2) by GC-MS using a 100-m polar capillary column. Rumenic acid would represent more than 75% of total CLA. 11-trans 13-trans, 11-13 cis/trans plus trans/cis and 7-9 cis/trans plus trans/cis were the main CLA isomers after rumenic acid. Minor amounts of 8-10 and 10-12 C18:2 isomers were also found. Although most of the isomers were present in each herd's milk, differences in content were observed for some CLA species.

  7. Screening of new British thraustochytrids isolates for docosahexaenoic acid (DHA) production.

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    Marchan, Loris Fossier; Lee Chang, Kim J; Nichols, Peter D; Polglase, Jane L; Mitchell, Wilfrid J; Gutierrez, Tony

    2017-01-01

    Thraustochytrids isolated from hot tropical and sub-tropical waters have been well studied for DHA and biodiesel production in the last decades. However, little research has been performed on the oils of cold water thraustochytrids, in particular from the North Sea region. In this study, thraustochytrid strains from British waters showed high relative levels of omega-3 long-chain (≥C 20 ) polyunsaturated fatty acids (LC-PUFA), including docosahexaenoic acid (DHA, 22:6ω3). The relative levels of DHA (as % of total fatty acids, TFA) in the different British strains are hitherto amongst the highest recorded from any thraustochytrid screening study, with strain TL18 reaching up to 67% DHA in modified Glucose-Yeast Extract-Peptone (GYP) medium. At this screening stage, low final biomass and fatty acid yield were observed in modified GYP and MarChiquita-Brain Heart Broth (MCBHB), while PUFA profiles (as % of PUFA) remained unaltered regardless of the culture medium used. Hence, optimizing the medium and culture conditions to improve growth and lipid content, without impacting the relative percentage of DHA, has the potential to increase the final DHA concentration. With this in mind, three strains were identified as promising organisms for the production of DHA. In the context of possible future industrial exploitation involving a winterization step, we investigated the recycling of the residual oil for biodiesel use. To do this, a mathematical model was used to assess the intrinsic properties of the by-product oil. The results showed the feasibility of producing primary DHA-rich oil, assuming optimized conditions, while using the by-product oil for biodiesel use.

  8. Improved mitochondrial function with diet-induced increase in either docosahexaenoic acid or arachidonic acid in membrane phospholipids.

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    Ramzi J Khairallah

    Full Text Available Mitochondria can depolarize and trigger cell death through the opening of the mitochondrial permeability transition pore (MPTP. We recently showed that an increase in the long chain n3 polyunsaturated fatty acids (PUFA docosahexaenoic acid (DHA; 22:6n3 and depletion of the n6 PUFA arachidonic acid (ARA; 20:4n6 in mitochondrial membranes is associated with a greater Ca(2+ load required to induce MPTP opening. Here we manipulated mitochondrial phospholipid composition by supplementing the diet with DHA, ARA or combined DHA+ARA in rats for 10 weeks. There were no effects on cardiac function, or respiration of isolated mitochondria. Analysis of mitochondrial phospholipids showed DHA supplementation increased DHA and displaced ARA in mitochondrial membranes, while supplementation with ARA or DHA+ARA increased ARA and depleted linoleic acid (18:2n6. Phospholipid analysis revealed a similar pattern, particularly in cardiolipin. Tetralinoleoyl cardiolipin was depleted by 80% with ARA or DHA+ARA supplementation, with linoleic acid side chains replaced by ARA. Both the DHA and ARA groups had delayed Ca(2+-induced MPTP opening, but the DHA+ARA group was similar to the control diet. In conclusion, alterations in mitochondria membrane phospholipid fatty acid composition caused by dietary DHA or ARA was associated with a greater cumulative Ca(2+ load required to induced MPTP opening. Further, high levels of tetralinoleoyl cardiolipin were not essential for normal mitochondrial function if replaced with very-long chain n3 or n6 PUFAs.

  9. Does docosahexaenoic acid supplementation in term infants enhance neurocognitive functioning in infancy?

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    Heaton, Alexandra E; Meldrum, Suzanne J; Foster, Jonathan K; Prescott, Susan L; Simmer, Karen

    2013-11-20

    The proposal that dietary docosahexaenoic acid (DHA) enhances neurocognitive functioning in term infants is controversial. Theoretical evidence, laboratory research and human epidemiological studies have convincingly demonstrated that DHA deficiency can negatively impact neurocognitive development. However, the results from randomized controlled trials (RCTs) of DHA supplementation in human term-born infants have been inconsistent. This article will (i) discuss the role of DHA in the human diet, (ii) explore the physiological mechanisms by which DHA plausibly influences neurocognitive capacity, and (iii) seek to characterize the optimal intake of DHA during infancy for neurocognitive functioning, based on existing research that has been undertaken in developed countries (specifically, within Australia). The major observational studies and RCTs that have examined dietary DHA in human infants and animals are presented, and we consider suggestions that DHA requirements vary across individuals according to genetic profile. It is important that the current evidence concerning DHA supplementation is carefully evaluated so that appropriate recommendations can be made and future directions of research can be strategically planned.

  10. Does docosahexaenoic acid supplementation in term infants enhance neurocognitive functioning in infancy?

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    Alexandra Elizabeth Heaton

    2013-11-01

    Full Text Available The proposal that dietary docosahexaenoic acid (DHA enhances neurocognitive functioning in term infants is controversial. Theoretical evidence, laboratory research and human epidemiological studies have convincingly demonstrated that DHA deficiency can negatively impact neurocognitive development. However, the results from randomized controlled trials (RCTs of DHA supplementation in human term-born infants have been inconsistent. This article will i discuss the role of DHA in the human diet, ii explore the physiological mechanisms by which DHA plausibly influences neurocognitive capacity and iii seek to characterize the optimal intake of DHA during infancy for neurocognitive functioning, based on existing research that has been undertaken in developed countries (specifically, within Australia. The major observational studies and RCTs that have examined dietary DHA in human infants and animals are presented, and we consider suggestions that DHA requirements vary across individuals according to genetic profile. It is important that the current evidence concerning DHA supplementation is carefully evaluated so that appropriate recommendations can be made and future directions of research can be strategically planned.

  11. Docosahexaenoic acid inhibits monocrotaline-induced pulmonary hypertension via attenuating endoplasmic reticulum stress and inflammation.

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    Chen, Rui; Zhong, Wei; Shao, Chen; Liu, Peijing; Wang, Cuiping; Wang, Zhongqun; Jiang, Meiping; Lu, Yi; Yan, Jinchuan

    2018-02-01

    Endoplasmic reticulum (ER) stress and inflammation contribute to pulmonary hypertension (PH) pathogenesis. Previously, we confirmed that docosahexaenoic acid (DHA) could improve hypoxia-induced PH. However, little is known about the link between DHA and monocrotaline (MCT)-induced PH. Our aims were, therefore, to evaluate the effects and molecular mechanisms of DHA on MCT-induced PH in rats. Rat PH was induced by MCT. Rats were treated with DHA daily in the prevention group (following MCT injection) and the reversal group (after MCT injection for 2 wk) by gavage. After 4 wk, mean pulmonary arterial pressure (mPAP), right ventricular (RV) hypertrophy index, and morphological and immunohistochemical analyses were evaluated. Rat pulmonary artery smooth muscle cells (PASMCs) were used to investigate the effects of DHA on cell proliferation stimulated by platelet-derived growth factor (PDGF)-BB. DHA decreased mPAP and attenuated pulmonary vascular remodeling and RV hypertrophy, which were associated with suppressed ER stress. DHA blocked the mitogenic effect of PDGF-BB on PASMCs and arrested the cell cycle via inhibiting nuclear factor of activated T cells-1 (NFATc1) expression and activation and regulating cell cycle-related proteins. Moreover, DHA ameliorated inflammation in lung and suppressed macrophage and T lymphocyte accumulation in lung and adventitia of resistance pulmonary arteries. These findings suggest that DHA could protect against MCT-induced PH by reducing ER stress, suppressing cell proliferation and inflammation.

  12. Effect of dietary docosahexaenoic acid connecting phospholipids on the lipid peroxidation of the brain in mice.

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    Hiratsuka, Seiichi; Ishihara, Kenji; Kitagawa, Tomoko; Wada, Shun; Yokogoshi, Hidehiko

    2008-12-01

    The effect of dietary docosahexaenoic acid (DHA, C22:6n-3) with two lipid types on lipid peroxidation of the brain was investigated in streptozotocin (STZ)-induced diabetic mice. Each group of female Balb/c mice was fed a diet containing DHA-connecting phospholipids (DHA-PL) or DHA-connecting triacylglycerols (DHA-TG) for 5 wk. Safflower oil was fed as the control. The lipid peroxide level of the brain was significantly lower in the mice fed the DHA-PL diet when compared to those fed the DHA-TG and safflower oil diets, while the alpha-tocopherol level was significantly higher in the mice fed the DHA-PL diet than in those fed the DHA-TG and safflower oil diets. The DHA level of phosphatidylethanolamine in the brain was significantly higher in the mice fed the DHA-PL diet than in those fed the safflower oil diet. The dimethylacetal levels were significantly higher in the mice fed the DHA-PL diet than in those fed the safflower oil and DHA-TG diets. These results suggest that the dietary DHA-connecting phospholipids have an antioxidant activity on the brain lipids in mice, and the effect may be related to the brain plasmalogen.

  13. Regulation of Ecto-5´-Nucleotidase by Docosahexaenoic Acid in Human Endothelial Cells

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    Vu Thi Thom

    2013-08-01

    Full Text Available Background/Aims: Modulation of extracellular adenine nucleotide and adenosine concentrations is one potential mechanism by which docosahexaenoic acid (DHA may exert beneficial effects in critically ill patients. This study assessed DHA effects on extracellular adenine purines. Methods: Experiments used human pulmonary endothelial cells (HPMEC and umbilical vein endothelial cells (HUVEC treated with DHA (48 h. mRNA level (real-time PCR, expression (western blot, flow cytometry and activities (hydrolysis of etheno(ε-purines and fluorescence HPLC of CD73 (ecto-5´-nucleotidase and CD39 (ecto-NTPDase-1 were quantified. Results: DHA elevated total CD73 membrane protein expression concentration-dependently but CD73 mRNA level did not change. Increased expression was paralleled by increased enzyme activity. Effects observed on membrane level were reversed in intact cells, in which ε-AMP hydrolysis decreased after DHA. In intact endothelial cells ATP release was enhanced and CD39 activity blunted following DHA treatment. Hence, extracellular ATP and ADP concentrations increased and this inhibited ε-AMP hydrolysis. Conclusion: In human endothelial cells DHA caused 1 up-regulation of CD73 protein content and increased AMP hydrolysis at the cell membrane level, 2 increased cellular ATP release, and 3 decreased extracellular ATP/ADP hydrolysis. Thus, reorganization of the extracellular adenine-nucleotide-adenosine axis in response to DHA resulted in an increased extracellular ATP/adenosine ratio.

  14. High-dose docosahexaenoic acid supplementation of preterm infants: respiratory and allergy outcomes.

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    Manley, Brett J; Makrides, Maria; Collins, Carmel T; McPhee, Andrew J; Gibson, Robert A; Ryan, Philip; Sullivan, Thomas R; Davis, Peter G

    2011-07-01

    Docosahexaenoic acid (DHA) has been associated with downregulation of inflammatory responses. To report the effect of DHA supplementation on long-term atopic and respiratory outcomes in preterm infants. This study is a multicenter, randomized controlled trial comparing the outcomes for preterm infants DHA diet) or soy oil (standard-DHA) capsules. Data collected included incidence of bronchopulmonary dysplasia (BPD) and parental reporting of atopic conditions over the first 18 months of life. Six hundred fifty-seven infants were enrolled (322 to high-DHA diet, 335 to standard), and 93.5% completed the 18-month follow-up. There was a reduction in BPD in boys (relative risk [RR]: 0.67 [95% confidence interval (CI): 0.47-0.96]; P=.03) and in all infants with a birth weight of DHA group at either 12 or 18 months (RR: 0.41 [95% CI: 0.18-0.91]; P=.03) and at either 12 or 18 months in boys (RR: 0.15 [0.03-0.64]; P=.01). There was no effect on asthma, eczema, or food allergy. DHA supplementation for infants of Pediatrics.

  15. α-Synuclein oligomers induced by docosahexaenoic acid affect membrane integrity.

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    Chiara Fecchio

    Full Text Available A key feature of Parkinson disease is the aggregation of α-synuclein and its intracellular deposition in fibrillar form. Increasing evidence suggests that the pathogenicity of α-synuclein is correlated with the activity of oligomers formed in the early stages of its aggregation process. Oligomers toxicity seems to be associated with both their ability to bind and affect the integrity of lipid membranes. Previously, we demonstrated that α-synuclein forms oligomeric species in the presence of docosahexaenoic acid and that these species are toxic to cells. Here we studied how interaction of these oligomers with membranes results in cell toxicity, using cellular membrane-mimetic and cell model systems. We found that α-synuclein oligomers are able to interact with large and small unilamellar negatively charged vesicles acquiring an increased amount of α-helical structure, which induces small molecules release. We explored the possibility that oligomers effects on membranes could be due to pore formation, to a detergent-like effect or to fibril growth on the membrane. Our biophysical and cellular findings are consistent with a model where α-synuclein oligomers are embedded into the lipid bilayer causing transient alteration of membrane permeability.

  16. Maternal Docosahexaenoic Acid Increases Adiponectin and Normalizes IUGR-Induced Changes in Rat Adipose Deposition

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    Heidi N. Bagley

    2013-01-01

    Full Text Available Intrauterine growth restriction (IUGR predisposes to obesity and adipose dysfunction. We previously demonstrated IUGR-induced increased visceral adipose deposition and dysregulated expression of peroxisome proliferator activated receptor-γ2 (PPARγ2 in male adolescent rats, prior to the onset of obesity. In other studies, activation of PPARγ increases subcutaneous adiponectin expression and normalizes visceral adipose deposition. We hypothesized that maternal supplementation with docosahexaenoic acid (DHA, a PPARγ agonist, would normalize IUGR adipose deposition in association with increased PPARγ, adiponectin, and adiponectin receptor expression in subcutaneous adipose. To test these hypotheses, we used a well-characterized model of uteroplacental-insufficiency-(UPI- induced IUGR in the rat with maternal DHA supplementation. Our primary findings were that maternal DHA supplementation during rat pregnancy and lactation (1 normalizes IUGR-induced changes in adipose deposition and visceral PPARγ expression in male rats and (2 increases serum adiponectin, as well as adipose expression of adiponectin and adiponectin receptors in former IUGR rats. Our novel findings suggest that maternal DHA supplementation may normalize adipose dysfunction and promote adiponectin-induced improvements in metabolic function in IUGR.

  17. Maternal docosahexaenoic acid increases adiponectin and normalizes IUGR-induced changes in rat adipose deposition.

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    Bagley, Heidi N; Wang, Yan; Campbell, Michael S; Yu, Xing; Lane, Robert H; Joss-Moore, Lisa A

    2013-01-01

    Intrauterine growth restriction (IUGR) predisposes to obesity and adipose dysfunction. We previously demonstrated IUGR-induced increased visceral adipose deposition and dysregulated expression of peroxisome proliferator activated receptor- γ 2 (PPAR γ 2) in male adolescent rats, prior to the onset of obesity. In other studies, activation of PPAR γ increases subcutaneous adiponectin expression and normalizes visceral adipose deposition. We hypothesized that maternal supplementation with docosahexaenoic acid (DHA), a PPAR γ agonist, would normalize IUGR adipose deposition in association with increased PPAR γ , adiponectin, and adiponectin receptor expression in subcutaneous adipose. To test these hypotheses, we used a well-characterized model of uteroplacental-insufficiency-(UPI-) induced IUGR in the rat with maternal DHA supplementation. Our primary findings were that maternal DHA supplementation during rat pregnancy and lactation (1) normalizes IUGR-induced changes in adipose deposition and visceral PPAR γ expression in male rats and (2) increases serum adiponectin, as well as adipose expression of adiponectin and adiponectin receptors in former IUGR rats. Our novel findings suggest that maternal DHA supplementation may normalize adipose dysfunction and promote adiponectin-induced improvements in metabolic function in IUGR.

  18. Docosahexaenoic Acid (DHA) Provides Neuroprotection in Traumatic Brain Injury Models via Activating Nrf2-ARE Signaling.

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    Zhu, Wei; Ding, Yuexia; Kong, Wei; Li, Tuo; Chen, Hongguang

    2018-04-16

    In this study, we explored the neuroprotective effects of docosahexaenoic acid (DHA) in traumatic brain injury (TBI) models. In this study, we first confirmed that DHA was neuroprotective against TBI via the NSS test and Morris water maze experiment. Western blot was conducted to identify the expression of Bax, caspase-3, and Bcl-2. And the cell apoptosis of the TBI models was validated by TUNEL staining. Relationships between nuclear factor erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE) pathway-related genes and DHA were explored by RT-PCR and Western blot. Rats of the DHA group performed remarkably better than those of the TBI group in both NSS test and water maze experiment. DHA conspicuously promoted the expression of Bcl-2 and diminished that of cleaved caspase-3 and Bax, indicating the anti-apoptotic role of DHA. Superoxide dismutase (SOD) activity and cortical malondialdehyde content, glutathione peroxidase (GPx) activity were renovated in rats receiving DHA treatment, implying that the neuroprotective influence of DHA was derived from lightening the oxidative stress caused by TBI. Moreover, immunofluorescence and Western blot experiments revealed that DHA facilitated the translocation of Nrf2 to the nucleus. DHA administration also notably increased the expression of the downstream factors NAD(P)H:quinone oxidoreductase (NQO-1) and heme oxygenase 1(HO-1). DHA exerted neuroprotective influence on the TBI models, potentially through activating the Nrf2- ARE pathway.

  19. Local anesthetic effect of docosahexaenoic acid on the nociceptive jaw-opening reflex in rats.

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    Mitome, Kazuki; Takehana, Shiori; Oshima, Katsuo; Shimazu, Yoshihito; Takeda, Mamoru

    2018-02-23

    Although docosahexaenoic acid (DHA) administration suppresses sodium channels in primary afferent sensory neurons, the acute local effect of DHA on the trigeminal nociceptive reflex remains to be elucidated, in vivo. Therefore, the aim of the present study was to investigate whether local administration of DHA attenuates the nociceptive jaw-opening reflex (JOR) in vivo in the rat. The JOR evoked by electrical stimulation of the tongue was recorded by a digastric muscle electromyogram (dEMG) in pentobarbital-anesthetized rats. The amplitude of the dEMG response was significantly increased in proportion to the electrical stimulation intensity (1-5 x threshold). At 3 x threshold, local administration of DHA (0.1, 10 and 25 mM) dose-dependently inhibited the dEMG response, and lasted 40 min. Maximum inhibition of the dEMG signal amplitude was seen within approximately 10 min. The mean magnitude of inhibition of the dEMG signal amplitude by DHA (25 mM) was almost equal to the local anesthetic, 1% lidocaine (37 mM), a sodium channel blocker. These findings suggest that DHA attenuates the nociceptive JOR via possibly blocking sodium channels, and strongly support the idea that DHA is a potential therapeutic agent and complementary alternative medicine for the prevention of acute trigeminal nociception. Copyright © 2018 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.

  20. Docosahexaenoic acid and adult memory: a systematic review and meta-analysis.

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    Karin Yurko-Mauro

    Full Text Available Subjective memory complaints are common with aging. Docosahexaenoic acid (DHA; 22:6 n-3 is a long-chain polyunsaturated fatty acid (LCPUFA and an integral part of neural membrane phospholipids that impacts brain structure and function. Past research demonstrates a positive association between DHA plasma status/dietary intake and cognitive function.The current meta-analysis was designed to determine the effect of DHA intake, alone or combined with eicosapentaenoic acid (EPA; 20:5 n-3, on specific memory domains: episodic, working, and semantic in healthy adults aged 18 years and older. A secondary objective was to systematically review/summarize the related observational epidemiologic literature.A systematic literature search of clinical trials and observational studies that examined the relationship between n-3 LCPUFA on memory outcomes in healthy adults was conducted in Ovid MEDLINE and EMBASE databases. Studies of subjects free of neurologic disease at baseline, with or without mild memory complaints (MMC, were included. Random effects meta-analyses were conducted to generate weighted group mean differences, standardized weighted group mean differences (Hedge's g, z-scores, and p-values for heterogeneity comparing DHA/EPA to a placebo. A priori sub-group analyses were conducted to evaluate the effect of age at enrollment, dose level, and memory type tested.Episodic memory outcomes of adults with MMC were significantly (P 1 g/day DHA/EPA improved episodic memory (P<.04. Semantic and working memory changes from baseline were significant with DHA but no between group differences were detected. Observational studies support a beneficial association between intake/blood levels of DHA/EPA and memory function in older adults.DHA, alone or combined with EPA, contributes to improved memory function in older adults with mild memory complaints.

  1. Early docosahexaenoic and arachidonic acid supplementation in extremely-low-birth-weight infants.

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    Robinson, Daniel T; Caplan, Michael; Carlson, Susan E; Yoder, Rachel; Murthy, Karna; Frost, Brandy

    2016-10-01

    Extremely-low-birth-weight (ELBW) infants accrue large deficits in docosahexaenoic acid (DHA) and arachidonic acid (ARA) and require improved supplementation strategies. We hypothesized that once daily DHA+ARA drops applied to buccal mucosa will increase blood levels. Thirty ELBW infants were randomized to receive DHA 20 mg/kg/d + ARA 40 or 60 mg/kg/d + ARA 120 mg/kg/d or placebo within 72 h of age for 8 wk duration. Red blood cell phospholipid levels of DHA (primary) and ARA (secondary) were measured at 2 and 8 wk of age. Twenty-eight survivors with a median birth weight of 806 g completed dosing and sampling. Red blood cell levels were similar between the three groups at 2 wk (DHA: 4.62 wt% (interquartile range (IQR) 4.1-5.5) for all, P = 0.29 between groups; ARA: 21.1 wt% (IQR 18.78-22.6) for all, P = 0.41 between groups) and 8 wk (DHA: 6.0 wt% (IQR 5.1-7.1) for all, P = 0.57 between groups; ARA: 20.1 wt% (IQR 18.3-23.1) for all, P = 0.63 between groups). DHA in all infants showed a median increase of 31% from 2 to 8 wk (P 0.6). Daily buccal DHA and ARA supplements did not affect fatty acid levels in ELBW infants.

  2. Dietary Crude Lecithin Increases Systemic Availability of Dietary Docosahexaenoic Acid with Combined Intake in Rats.

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    van Wijk, Nick; Balvers, Martin; Cansev, Mehmet; Maher, Timothy J; Sijben, John W C; Broersen, Laus M

    2016-07-01

    Crude lecithin, a mixture of mainly phospholipids, potentially helps to increase the systemic availability of dietary omega-3 polyunsaturated fatty acids (n-3 PUFA), such as docosahexaenoic acid (DHA). Nevertheless, no clear data exist on the effects of prolonged combined dietary supplementation of DHA and lecithin on RBC and plasma PUFA levels. In the current experiments, levels of DHA and choline, two dietary ingredients that enhance neuronal membrane formation and function, were determined in plasma and red blood cells (RBC) from rats after dietary supplementation of DHA-containing oils with and without concomitant dietary supplementation of crude lecithin for 2-3 weeks. The aim was to provide experimental evidence for the hypothesized additive effects of dietary lecithin (not containing any DHA) on top of dietary DHA on PUFA levels in plasma and RBC. Dietary supplementation of DHA-containing oils, either as vegetable algae oil or as fish oil, increased DHA, eicosapentaenoic acid (EPA), and total n-3 PUFA, and decreased total omega-6 PUFA levels in plasma and RBC, while dietary lecithin supplementation alone did not affect these levels. However, combined dietary supplementation of DHA and lecithin increased the changes induced by DHA supplementation alone. Animals receiving a lecithin-containing diet also had a higher plasma free choline concentration as compared to controls. In conclusion, dietary DHA-containing oils and crude lecithin have synergistic effects on increasing plasma and RBC n-3 PUFA levels, including DHA and EPA. By increasing the systemic availability of dietary DHA, dietary lecithin may increase the efficacy of DHA supplementation when their intake is combined.

  3. Docosahexaenoic acid (DHA): An essential nutrient and a nutraceutical for brain health and diseases.

    Science.gov (United States)

    Sun, Grace Y; Simonyi, Agnes; Fritsche, Kevin L; Chuang, Dennis Y; Hannink, Mark; Gu, Zezong; Greenlief, C Michael; Yao, Jeffrey K; Lee, James C; Beversdorf, David Q

    2017-03-10

    Docosahexaenoic acid (DHA), a polyunsaturated fatty acid (PUFA) enriched in phospholipids in the brain and retina, is known to play multi-functional roles in brain health and diseases. While arachidonic acid (AA) is released from membrane phospholipids by cytosolic phospholipase A 2 (cPLA 2 ), DHA is linked to action of the Ca 2+ -independent iPLA2. DHA undergoes enzymatic conversion by 15-lipoxygenase (Alox 15) to form oxylipins including resolvins and neuroprotectins, which are powerful lipid mediators. DHA can also undergo non-enzymatic conversion by reacting with oxygen free radicals (ROS), which cause the production of 4-hydoxyhexenal (4-HHE), an aldehyde derivative which can form adducts with DNA, proteins and lipids. In studies with both animal models and humans, there is evidence that inadequate intake of maternal n-3 PUFA may lead to aberrant development and function of the central nervous system (CNS). What is less certain is whether consumption of n-3 PUFA is important in maintaining brain health throughout one's life span. Evidence mostly from non-human studies suggests that DHA intake above normal nutritional requirements might modify the risk/course of a number of diseases of the brain. This concept has fueled much of the present interest in DHA research, in particular, in attempts to delineate mechanisms whereby DHA may serve as a nutraceutical and confer neuroprotective effects. Current studies have revealed ability for the oxylipins to regulation of cell redox homeostasis through the Nuclear factor (erythroid-derived 2)-like 2/Antioxidant response element (Nrf2/ARE) anti-oxidant pathway, and impact signaling pathways associated with neurotransmitters, and modulation of neuronal functions involving brain-derived neurotropic factor (BDNF). This review is aimed at describing recent studies elaborating these mechanisms with special regard to aging and Alzheimer's disease, autism spectrum disorder, schizophrenia, traumatic brain injury, and stroke

  4. Randomized controlled trial of docosahexaenoic acid supplementation in midwestern U.S. human milk donors.

    Science.gov (United States)

    Valentine, Christina J; Morrow, Georgia; Pennell, Michael; Morrow, Ardythe L; Hodge, Amanda; Haban-Bartz, Annette; Collins, Kristin; Rogers, Lynette K

    2013-02-01

    Docosahexaenoic acid (DHA) is a long-chain polyunsaturated fatty acid important for neonatal neurodevelopment and immune homeostasis. Preterm infants fed donor milk from a Midwestern source receive only 20% of the intrauterine accretion of DHA. We tested the hypothesis that DHA supplementation of donor mothers would provide preterm infants with DHA intake equivalent to fetal accretion. After Institutional Review Board approval and informed consent, human milk donors to the Mother's Milk Bank of Ohio were randomized to receive 1 g of DHA (Martek(®) [now DSM Nutritional Lipids, Columbia, MD]) or placebo soy oil. Dietary intake data were collected and analyzed by a registered dietitian. Fatty acids were measured by gas chromatography/flame ionization detection. Statistical analysis used linear mixed models. Twenty-one mothers were randomly assigned to either the DHA group (n=10) or the placebo group (n=11). Donor age was a median of 31 years in both groups with a mean lactational stage of 19 weeks. Dietary intake of DHA at baseline in both groups was a median of 23 mg/day (range, 0-194 mg), significantly (p<0.0001) less than the minimum recommended intake of 200 mg/day. The DHA content of milk increased in the DHA-supplemented group (p<0.05). The women enrolled in this study had low dietary DHA intake. Supplementation with preformed DHA at 1 g/day resulted in increased DHA concentrations in the donor milk with no adverse outcomes. Infants fed donor milk from supplemented women receive dietary DHA levels that closely mimic normal intrauterine accretion during the third trimester.

  5. 4-Hydroxy hexenal derived from docosahexaenoic acid protects endothelial cells via Nrf2 activation.

    Directory of Open Access Journals (Sweden)

    Atsushi Ishikado

    Full Text Available Recent studies have proposed that n-3 polyunsaturated fatty acids (n-3 PUFAs have direct antioxidant and anti-inflammatory effects in vascular tissue, explaining their cardioprotective effects. However, the molecular mechanisms are not yet fully understood. We tested whether n-3 PUFAs showed antioxidant activity through the activation of nuclear factor erythroid 2-related factor 2 (Nrf2, a master transcriptional factor for antioxidant genes. C57BL/6 or Nrf2(-/- mice were fed a fish-oil diet for 3 weeks. Fish-oil diet significantly increased the expression of heme oxygenase-1 (HO-1, and endothelium-dependent vasodilation in the aorta of C57BL/6 mice, but not in the Nrf2(-/- mice. Furthermore, we observed that 4-hydroxy hexenal (4-HHE, an end-product of n-3 PUFA peroxidation, was significantly increased in the aorta of C57BL/6 mice, accompanied by intra-aortic predominant increase in docosahexaenoic acid (DHA rather than that in eicosapentaenoic acid (EPA. Human umbilical vein endothelial cells were incubated with DHA or EPA. We found that DHA, but not EPA, markedly increased intracellular 4-HHE, and nuclear expression and DNA binding of Nrf2. Both DHA and 4-HHE also increased the expressions of Nrf2 target genes including HO-1, and the siRNA of Nrf2 abolished these effects. Furthermore, DHA prevented oxidant-induced cellular damage or reactive oxygen species production, and these effects were disappeared by an HO-1 inhibitor or the siRNA of Nrf2. Thus, we found protective effects of DHA through Nrf2 activation in vascular tissue, accompanied by intra-vascular increases in 4-HHE, which may explain the mechanism of the cardioprotective effects of DHA.

  6. Docosahexaenoic acid loaded lipid nanoparticles with bactericidal activity against Helicobacter pylori.

    Science.gov (United States)

    Seabra, Catarina Leal; Nunes, Cláudia; Gomez-Lazaro, Maria; Correia, Marta; Machado, José Carlos; Gonçalves, Inês C; Reis, Celso A; Reis, Salette; Martins, M Cristina L

    2017-03-15

    Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid present in fish oil, has been described as a promising molecule to the treatment of Helicobacter pylori gastric infection. However, due to its highly unsaturated structure, DHA can be easily oxidized loosing part of its bioactivity. This work aims the nanoencapsulation of DHA to improve its bactericidal efficacy against H. pylori. DHA was loaded into nanostructured lipid carriers (NLC) produced by hot homogenization and ultrasonication using a blend of lipids (Precirol ATO5 ® , Miglyol-812 ® ) and a surfactant (Tween 60 ® ). Homogeneous NLC with 302±14nm diameter, -28±3mV surface charge (dynamic and electrophoretic light scattering) and containing 66±7% DHA (UV/VIS spectroscopy) were successfully produced. Bacterial growth curves, performed over 24h in the presence of different DHA concentrations (free or loaded into NLC), demonstrated that nanoencapsulation enhanced DHA bactericidal effect, since DHA-loaded NLC were able to inhibit H. pylori growth in a much lower concentrations (25μM) than free DHA (>100μM). Bioimaging studies, using scanning and transmission electron microscopy and also imaging flow cytometry, demonstrated that DHA-loaded NLC interact with H. pylori membrane, increasing their periplasmic space and disrupting membrane and allowing the leakage of cytoplasmic content. Furthermore, the developed nanoparticles are not cytotoxic to human gastric adenocarcinoma cells at bactericidal concentrations. DHA-loaded NLC should, therefore, be envisaged as an alternative to the current treatments for H. pylori infection. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. The therapeutic effects of docosahexaenoic acid on oestrogen/androgen-induced benign prostatic hyperplasia in rats

    International Nuclear Information System (INIS)

    Wang, Chao; Luo, Fei; Zhou, Ying; Du, Xiaoling; Shi, Jiandang; Zhao, Xiaoling; Xu, Yong; Zhu, Yan; Hong, Wei; Zhang, Ju

    2016-01-01

    Benign prostatic hyperplasia (BPH) is one of the major disorders of the urinary system in elderly men. Docosahexaenoic acid (DHA) is the main component of n-3 polyunsaturated fatty acids (n-3 PUFAs) and has nerve protective, anti-inflammatory and tumour-growth inhibitory effects. Here, the therapeutic potential of DHA in treating BPH was investigated. Seal oil effectively prevented the development of prostatic hyperplasia induced by oestradiol/testosterone in a rat model by suppressing the increase of the prostatic index (PI), reducing the thickness of the peri-glandular smooth muscle layer, inhibiting the proliferation of both prostate epithelial and stromal cells, and downregulating the expression of androgen receptor (AR) and oestrogen receptor α (ERα). An in vitro study showed that DHA inhibited the growth of the human prostate stromal cell line WPMY-1 and the epithelial cell line RWPE-1 in a dose- and time-dependent manner. In both cell lines, the DHA arrested the cell cycle in the G2/M phase. In addition, DHA also reduced the expression of ERα and AR in the WPMY-1 and RWPE-1 cells. These results indicate that DHA inhibits the multiplication of prostate stromal and epithelial cells through a mechanism that may involve cell cycle arrest and the downregulation of ERα and AR expression. - Highlights: • Seal oil prevents oestradiol/testosterone (E2/T)-induced BPH in castrated rats. • Seal oil downregulates the expression of oestrogen receptor α(ERα) and androgen receptor (AR) in rat BPH tissues. • DHA inhibits the growth of human prostate stromal and epithelial cells in vitro. • DHA arrests human prostate stromal and epithelial cells in the G2/M phase and downregulates the expression of cyclin B1. • DHA inhibits the expression of ERα and AR in human prostate stromal and epithelial cells.

  8. Role of docosahexaenoic acid treatment in improving liver histology in pediatric nonalcoholic fatty liver disease.

    Science.gov (United States)

    Nobili, Valerio; Carpino, Guido; Alisi, Anna; De Vito, Rita; Franchitto, Antonio; Alpini, Gianfranco; Onori, Paolo; Gaudio, Eugenio

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is one of the most important causes of liver-related morbidity and mortality in children. Recently, we have reported the effects of docosahexaenoic acid (DHA), the major dietary long-chain polyunsaturated fatty acids, in children with NAFLD. DHA exerts a potent anti-inflammatory activity through the G protein-coupled receptor (GPR)120. Our aim was to investigate in pediatric NAFLD the mechanisms underlying the effects of DHA administration on histo-pathological aspects, GPR120 expression, hepatic progenitor cell activation and macrophage pool. 20 children with untreated NAFLD were included. Children were treated with DHA for 18 months. Liver biopsies before and after the treatment were analyzed. Hepatic progenitor cell activation, macrophage pool and GPR120 expression were evaluated and correlated with clinical and histo-pathological parameters. GPR120 was expressed by hepatocytes, liver macrophages, and hepatic progenitor cells. After DHA treatment, the following modifications were present: i) the improvement of histo-pathological parameters such as NAFLD activity score, ballooning, and steatosis; ii) the reduction of hepatic progenitor cell activation in correlation with histo-pathological parameters; iii) the reduction of the number of inflammatory macrophages; iv) the increase of GPR120 expression in hepatocytes; v) the reduction of serine-311-phosphorylated nuclear factor kappa B (NF-κB) nuclear translocation in hepatocytes and macrophages in correlation with serum inflammatory cytokines. DHA could modulate hepatic progenitor cell activation, hepatocyte survival and macrophage polarization through the interaction with GPR120 and NF-κB repression. In this scenario, the modulation of GPR120 exploits a novel crucial role in the regulation of the cell-to-cell cross-talk that drives inflammatory response, hepatic progenitor cell activation and hepatocyte survival.

  9. Role of docosahexaenoic acid treatment in improving liver histology in pediatric nonalcoholic fatty liver disease.

    Directory of Open Access Journals (Sweden)

    Valerio Nobili

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is one of the most important causes of liver-related morbidity and mortality in children. Recently, we have reported the effects of docosahexaenoic acid (DHA, the major dietary long-chain polyunsaturated fatty acids, in children with NAFLD. DHA exerts a potent anti-inflammatory activity through the G protein-coupled receptor (GPR120. Our aim was to investigate in pediatric NAFLD the mechanisms underlying the effects of DHA administration on histo-pathological aspects, GPR120 expression, hepatic progenitor cell activation and macrophage pool.20 children with untreated NAFLD were included. Children were treated with DHA for 18 months. Liver biopsies before and after the treatment were analyzed. Hepatic progenitor cell activation, macrophage pool and GPR120 expression were evaluated and correlated with clinical and histo-pathological parameters.GPR120 was expressed by hepatocytes, liver macrophages, and hepatic progenitor cells. After DHA treatment, the following modifications were present: i the improvement of histo-pathological parameters such as NAFLD activity score, ballooning, and steatosis; ii the reduction of hepatic progenitor cell activation in correlation with histo-pathological parameters; iii the reduction of the number of inflammatory macrophages; iv the increase of GPR120 expression in hepatocytes; v the reduction of serine-311-phosphorylated nuclear factor kappa B (NF-κB nuclear translocation in hepatocytes and macrophages in correlation with serum inflammatory cytokines.DHA could modulate hepatic progenitor cell activation, hepatocyte survival and macrophage polarization through the interaction with GPR120 and NF-κB repression. In this scenario, the modulation of GPR120 exploits a novel crucial role in the regulation of the cell-to-cell cross-talk that drives inflammatory response, hepatic progenitor cell activation and hepatocyte survival.

  10. Docosahexaenoic acid counteracts attenuation of CD95-induced cell death by inorganic mercury

    International Nuclear Information System (INIS)

    Gill, Randall; Lanni, Lydia; Jen, K.-L. Catherine; McCabe, Michael J.; Rosenspire, Allen

    2015-01-01

    In the United States the principal environmental exposure to mercury is through dietary consumption of sea food. Although the mechanism by which low levels of mercury affect the nervous system is not well established, epidemiological studies suggest that low level exposure of pregnant women to dietary mercury can adversely impact cognitive development in their children, but that Docosahexaenoic acid (DHA), the most prominent n-polyunsaturated fatty acid (n-PUFA) present in fish may counteract negative effects of mercury on the nervous system. Aside from effects on the nervous system, epidemiological and animal studies have also suggested that low level mercury exposure may be a risk factor for autoimmune disease. However unlike the nervous system where a mechanism linking mercury to impaired cognitive development remains elusive, we have previously suggested a potential mechanism linking low level mercury exposures to immune system dysfunction and autoimmunity. In the immune system it is well established that disruption of CD95 mediated apoptosis leads to autoimmune disease. We have previously shown in vitro as well as in vivo that in lymphocytes burdened with low levels of mercury, CD95 mediated cell death is impaired. In this report we now show that DHA counteracts the negative effect of mercury on CD95 signaling in T lymphocytes. T cells which have been pre-exposed to DHA are able to cleave pro-caspase 3 and efficiently signal programmed cell death through the CD95 signaling pathway, whether or not they are burdened with low levels of mercury. Thus DHA may lower the risk of autoimmune disease after low level mercury exposures. - Highlights: • Inorganic mercury (Hg 2+ ) interferes with CD95 mediated cell death in Jurkat T cells • DHA restores the ability of CD95 to signal cell death in Hg 2+ intoxicated T cells • The restoration of CD95 mediated cell death by DHA is correlated with increased activation of Caspase 3

  11. Docosahexaenoic acid counteracts attenuation of CD95-induced cell death by inorganic mercury

    Energy Technology Data Exchange (ETDEWEB)

    Gill, Randall [Department of Immunology and Microbiology, Wayne State University, Detroit MI (United States); Lanni, Lydia; Jen, K.-L. Catherine [Department of Nutrition and Food Science, Wayne State University, Detroit MI (United States); McCabe, Michael J. [Department of Environmental Medicine, University of Rochester, Rochester NY (United States); Rosenspire, Allen, E-mail: arosenspire@wayne.edu [Department of Immunology and Microbiology, Wayne State University, Detroit MI (United States)

    2015-01-01

    In the United States the principal environmental exposure to mercury is through dietary consumption of sea food. Although the mechanism by which low levels of mercury affect the nervous system is not well established, epidemiological studies suggest that low level exposure of pregnant women to dietary mercury can adversely impact cognitive development in their children, but that Docosahexaenoic acid (DHA), the most prominent n-polyunsaturated fatty acid (n-PUFA) present in fish may counteract negative effects of mercury on the nervous system. Aside from effects on the nervous system, epidemiological and animal studies have also suggested that low level mercury exposure may be a risk factor for autoimmune disease. However unlike the nervous system where a mechanism linking mercury to impaired cognitive development remains elusive, we have previously suggested a potential mechanism linking low level mercury exposures to immune system dysfunction and autoimmunity. In the immune system it is well established that disruption of CD95 mediated apoptosis leads to autoimmune disease. We have previously shown in vitro as well as in vivo that in lymphocytes burdened with low levels of mercury, CD95 mediated cell death is impaired. In this report we now show that DHA counteracts the negative effect of mercury on CD95 signaling in T lymphocytes. T cells which have been pre-exposed to DHA are able to cleave pro-caspase 3 and efficiently signal programmed cell death through the CD95 signaling pathway, whether or not they are burdened with low levels of mercury. Thus DHA may lower the risk of autoimmune disease after low level mercury exposures. - Highlights: • Inorganic mercury (Hg{sup 2+}) interferes with CD95 mediated cell death in Jurkat T cells • DHA restores the ability of CD95 to signal cell death in Hg{sup 2+} intoxicated T cells • The restoration of CD95 mediated cell death by DHA is correlated with increased activation of Caspase 3.

  12. Docosahexaenoic acid triglyceride-based microemulsions with an added dendrimer - Structural considerations.

    Science.gov (United States)

    Lidich, Nina; Francesca Ottaviani, M; Hoffman, Roy E; Aserin, Abraham; Garti, Nissim

    2016-12-01

    Omega fatty acids, mainly the triglyceride of docosahexaenoic acid (TG-DHA), are considered important nutraceuticals. These compounds are water-insoluble and their transport across membranes depends on their carriers. Dendrimers are known as drug carriers across cell membranes and also as permeation enhancers. The solubilization of TG-DHA and dendrimer into a microemulsion (ME) system serving as a carrier could be used for a targeted delivery in the future. The interactions between TG-DHA and second generation poly(propyleneimine) dendrimers (PPI-G2) and their effect on structural transitions of ME were explored along the water dilution line using electron paramagnetic resonance and pulsed-gradient spin-echo NMR along with other analytical techniques. The microviscosity, order parameter, and micropolarity of all studied systems decrease upon water dilution. Incorporation of TG-DHA reduces the microviscosity, order, and micropolarity, whereas PPI-G2 leads to an increase in these parameters. The effect of PPI-G2 is more pronounced at relative high contents (1 and 5wt%) where PPI-G2 interacts with the hydrophilic headgroups of the surfactants. In the macroscale, the effects of TG-DHA and PPI-G2 differ mostly in the bicontinuous region, where macroviscosity increases upon TG-DHA incorporation and decreases upon solubilization of 5wt% PPI-G2. From DSC measurements it was concluded that in the presence of TG-DHA the PPI-G2 is intercalated easily at the interface. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Docosahexaenoic acid alters Gsα localization in lipid raft and potentiates adenylate cyclase.

    Science.gov (United States)

    Zhu, Zhuoran; Tan, Zhoubin; Li, Yan; Luo, Hongyan; Hu, Xinwu; Tang, Ming; Hescheler, Jürgen; Mu, Yangling; Zhang, Lanqiu

    2015-01-01

    Supplementation with docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid (PUFA), recently has become popular for the amelioration of depression; however the molecular mechanism of DHA action remains unclear. The aim of this study was to investigate the mechanism underlying the antidepressant effect of DHA by evaluating Gsα localization in lipid raft and the activity of adenylate cyclase in an in vitro glioma cell model. Lipid raft fractions from C6 glioma cells treated chronically with DHA were isolated by sucrose gradient ultracentrifugation. The content of Gsα in lipid raft was analyzed by immunoblotting and colocalization of Gsα with lipid raft was subjected to confocal microscopic analysis. The intracellular cyclic adenosine monophosphate (cAMP) level was determined by cAMP immunoassay kit. DHA decreased the amount of Gsα in lipid raft, whereas whole cell lysate Gsα was not changed. Confocal microscopic analysis demonstrated that colocalization of Gsα with lipid raft was decreased, whereas DHA increased intracellular cAMP accumulation in a dose-dependent manner. Interestingly, we found that DHA increased the lipid raft level, instead of disrupting it. The results of this study suggest that DHA may exert its antidepressant effect by translocating Gsα from lipid raft and potentiating the activity of adenylate cyclase. Importantly, the reduced Gsα in lipid raft by DHA is independent of disruption of lipid raft. Overall, the study provides partial preclinical evidence supporting a safe and effective therapy using DHA for depression. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. The therapeutic effects of docosahexaenoic acid on oestrogen/androgen-induced benign prostatic hyperplasia in rats

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Chao [Department of Biochemistry and Molecular Biology, College of Life Sciences, Bioactive Materials Key Lab of Ministry of Education, Nankai University, Tianjin 300071 (China); Luo, Fei [Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211 (China); Zhou, Ying; Du, Xiaoling; Shi, Jiandang; Zhao, Xiaoling [Department of Biochemistry and Molecular Biology, College of Life Sciences, Bioactive Materials Key Lab of Ministry of Education, Nankai University, Tianjin 300071 (China); Xu, Yong [Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211 (China); Zhu, Yan [Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193 (China); Hong, Wei, E-mail: hongwei@tijmu.edu.cn [Department of Histology and Embryology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070 (China); Zhang, Ju, E-mail: zhangju@nankai.edu.cn [Department of Biochemistry and Molecular Biology, College of Life Sciences, Bioactive Materials Key Lab of Ministry of Education, Nankai University, Tianjin 300071 (China)

    2016-07-15

    Benign prostatic hyperplasia (BPH) is one of the major disorders of the urinary system in elderly men. Docosahexaenoic acid (DHA) is the main component of n-3 polyunsaturated fatty acids (n-3 PUFAs) and has nerve protective, anti-inflammatory and tumour-growth inhibitory effects. Here, the therapeutic potential of DHA in treating BPH was investigated. Seal oil effectively prevented the development of prostatic hyperplasia induced by oestradiol/testosterone in a rat model by suppressing the increase of the prostatic index (PI), reducing the thickness of the peri-glandular smooth muscle layer, inhibiting the proliferation of both prostate epithelial and stromal cells, and downregulating the expression of androgen receptor (AR) and oestrogen receptor α (ERα). An in vitro study showed that DHA inhibited the growth of the human prostate stromal cell line WPMY-1 and the epithelial cell line RWPE-1 in a dose- and time-dependent manner. In both cell lines, the DHA arrested the cell cycle in the G2/M phase. In addition, DHA also reduced the expression of ERα and AR in the WPMY-1 and RWPE-1 cells. These results indicate that DHA inhibits the multiplication of prostate stromal and epithelial cells through a mechanism that may involve cell cycle arrest and the downregulation of ERα and AR expression. - Highlights: • Seal oil prevents oestradiol/testosterone (E2/T)-induced BPH in castrated rats. • Seal oil downregulates the expression of oestrogen receptor α(ERα) and androgen receptor (AR) in rat BPH tissues. • DHA inhibits the growth of human prostate stromal and epithelial cells in vitro. • DHA arrests human prostate stromal and epithelial cells in the G2/M phase and downregulates the expression of cyclin B1. • DHA inhibits the expression of ERα and AR in human prostate stromal and epithelial cells.

  15. Concentration of eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA of Asian catfish oil by urea complexation: optimization of reaction conditions

    Directory of Open Access Journals (Sweden)

    Pornpisanu Thammapat

    2016-04-01

    Full Text Available Optimization of the concentrating conditions of eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA extracted from Asian catfish oil was studied to obtain a maximum concentration. The crude fish oil was extracted from the belly flap and adipose tissue of Asian catfish, and the extracted oil was used as fresh crude oil. The EPA and DHA were concentrated by the urea complexation method. A hexagonal rotatable design was applied to examine the effects of crystallization temperature and urea-to-fatty acid ratio on the total content of EPA and DHA (Y1 and the liquid recovery yield (Y2 . The second order polynomial regression models for Y1 and Y2 were employed to generate the response surfaces. Under the optimum conditions of -20 °C and a urea-to-fatty acid ratio of 4 (w/w, the total concentration of EPA and DHA could be increased by up to 88%, while a liquid recovery yield of 26% was obtained.

  16. Are conjugated linolenic acid isomers an alternative to conjugated linoleic acid isomers in obesity prevention?

    Science.gov (United States)

    Miranda, Jonatan; Arias, Noemi; Fernández-Quintela, Alfredo; del Puy Portillo, María

    2014-04-01

    Despite its benefits, conjugated linoleic acid (CLA) may cause side effects after long-term administration. Because of this and the controversial efficacy of CLA in humans, alternative biomolecules that may be used as functional ingredients have been studied in recent years. Thus, conjugated linolenic acid (CLNA) has been reported to be a potential anti-obesity molecule which may have additional positive effects related to obesity. According to the results reported in obesity, CLNA needs to be given at higher doses than CLA to be effective. However, because of the few studies conducted so far, it is still difficult to reach clear conclusions about the potential use of these CLNAs in obesity and its related changes (insulin resistance, dyslipidemia, or inflammation). Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  17. Effect of Eicosapentaenoic Acid and Docosahexaenoic Acid on Myogenesis and Mitochondrial Biosynthesis during Murine Skeletal Muscle Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Tun-Yun Hsueh

    2018-03-01

    Full Text Available Polyunsaturated fatty acids are important nutrients for human health, especially omega-3 fatty acids such as eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA, which have been found to play positive roles in the prevention of various diseases. However, previous studies have reported that excessive omega-3 fatty acids supplement during pregnancy caused side effects such as slower neural transmission times and postnatal growth restriction. In this study, we investigated the effect of EPA and DHA on mitochondrial function and gene expression in C2C12 myoblasts during skeletal muscle differentiation. C2C12 myoblasts were cultured to confluency and then treated with differentiation medium that contained fatty acids (50-µM EPA and DHA. After 72 h of myogenic differentiation, mRNA was collected, and gene expression was analyzed by real-time PCR. Microscopy was used to examine cell morphology following treatment with fatty acids. The effect of EPA and DHA on cellular oxygen consumption was measured using a Seahorse XF24 Analyzer. Cells treated with fatty acids had fewer myotubes formed (P ≤ 0.05 compared with control cells. The expression of the genes related to myogenesis was significantly lower (P ≤ 0.05 in cells treated with fatty acids, compared with control cells. Genes associated with adipogenesis had higher (P ≤ 0.05 expression after treatment with fatty acids. Also, the mitochondrial biogenesis decreased with lower (P ≤ 0.05 gene expression and lower (P ≤ 0.05 mtDNA/nDNA ratio in cells treated with fatty acids compared with control cells. However, the expression of genes related to peroxisome biosynthesis was higher (P ≤ 0.05 in cells treated with fatty acids. Moreover, fatty-acid treatment reduced (P ≤ 0.05 oxygen consumption rate under oligomycin-inhibited (reflecting proton leak and uncoupled conditions. Our data imply that fatty acids might reduce myogenesis and increase adipogenesis in myotube formation. Fatty acids

  18. Effects of Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) on Fetal Pulmonary Circulation: An Experimental Study in Fetal Lambs.

    Science.gov (United States)

    Sharma, Dyuti; Aubry, Estelle; Ouk, Thavarak; Houeijeh, Ali; Houfflin-Debarge, Véronique; Besson, Rémi; Deruelle, Philippe; Storme, Laurent

    2017-07-16

    Background: Persistent pulmonary hypertension of the newborn (PPHN) causes significant morbidity and mortality in neonates. n -3 Poly-unsaturated fatty acids have vasodilatory properties in the perinatal lung. We studied the circulatory effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in fetal sheep and in fetal pulmonary arterial rings. Methods: At 128 days of gestation, catheters were placed surgically in fetal systemic and pulmonary circulation, and a Doppler probe around the left pulmonary artery (LPA). Pulmonary arterial pressure and LPA flow were measured while infusing EPA or DHA for 120 min to the fetus, to compute pulmonary vascular resistance (PVR). The dose effects of EPA or DHA were studied in vascular rings pre-constricted with serotonin. Rings treated with EPA were separated into three groups: E+ (intact endothelium), E- (endothelium stripped) and LNA E+ (pretreatment of E+ rings with l-nitro-arginine). Results: EPA, but not DHA, induced a significant and prolonged 25% drop in PVR ( n = 8, p DHA resulted in only a mild relaxation at the highest concentration of DHA (300 µM) compared to E+. Conclusions: EPA induces a sustained pulmonary vasodilatation in fetal lambs. This effect is endothelium- and dose-dependent and involves nitric oxide (NO) production. We speculate that EPA supplementation may improve pulmonary circulation in clinical conditions with PPHN.

  19. Threshold changes in rat brain docosahexaenoic acid incorporation and concentration following graded reductions in dietary alpha-linolenic acid

    Science.gov (United States)

    Taha, Ameer Y.; Chang, Lisa; Chen, Mei

    2016-01-01

    Background This study tested the dietary level of alpha-linolenic acid (α-LNA, 18:3n-3) sufficient to maintain brain 14C-Docosahexaenoic acid (DHA, 22:6n-3) metabolism and concentration following graded α-LNA reduction. Methods 18–21 day male Fischer-344 (CDF) rats were randomized to the AIN-93G diet containing as a % of total fatty acids, 4.6% (“n-3 adequate”), 3.6%, 2.7%, 0.9% or 0.2% (“n-3 deficient”) α-LNA for 15 weeks. Rats were intravenously infused with 14C-DHA to steady state for 5 minutes, serial blood samples collected to obtain plasma and brains excised following microwave fixation. Labeled and unlabeled DHA concentrations were measured in plasma and brain to calculate the incorporation coefficient, k*, and incorporation rate, Jin. Results Compared to 4.6% α-LNA controls, k* was significantly increased in ethanolamine glycerophospholipids in the 0.2% α-LNA group. Circulating unesterified DHA and brain incorporation rates (Jin) were significantly reduced at 0.2% α-LNA. Brain total lipid and phospholipid DHA concentrations were reduced at or below 0.9% α-LNA. Conclusion Threshold changes for brain DHA metabolism and concentration were maintained at or below 0.9% dietary α-LNA, suggesting the presence of homeostatic mechanisms to maintain brain DHA metabolism when dietary α-LNA intake is low. PMID:26869088

  20. Docosahexaenoic acid (DHA) effects on proliferation and steroidogenesis of bovine granulosa cells.

    Science.gov (United States)

    Maillard, Virginie; Desmarchais, Alice; Durcin, Maeva; Uzbekova, Svetlana; Elis, Sebastien

    2018-04-26

    Docosahexaenoic acid (DHA) is a n-3 polyunsaturated fatty acid (PUFA) belonging to a family of biologically active fatty acids (FA), which are known to have numerous health benefits. N-3 PUFAs affect reproduction in cattle, and notably directly affect follicular cells. In terms of reproduction in cattle, n-3 PUFA-enriched diets lead to increased follicle size or numbers. The objective of the present study was to analyze the effects of DHA (1, 10, 20 and 50 μM) on proliferation and steroidogenesis (parametric and/or non parametric (permutational) ANOVA) of bovine granulosa cells in vitro and mechanisms of action through protein expression (Kruskal-Wallis) and signaling pathways (non parametric ANOVA) and to investigate whether DHA could exert part of its action through the free fatty acid receptor 4 (FFAR4). DHA (10 and 50 μM) increased granulosa cell proliferation and DHA 10 μM led to a corresponding increase in proliferating cell nuclear antigen (PCNA) expression level. DHA also increased progesterone secretion at 1, 20 and 50 μM, and estradiol secretion at 1, 10 and 20 μM. Consistent increases in protein levels were also reported for the steroidogenic enzymes, cytochrome P450 family 11 subfamily A member 1 (CYP11A1) and hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1 (HSD3B1), and of the cholesterol transporter steroidogenic acute regulatory protein (StAR), which are necessary for production of progesterone or androstenedione. FFAR4 was expressed in all cellular types of bovine ovarian follicles, and in granulosa cells it was localized close to the cellular membrane. TUG-891 treatment (1 and 50 μM), a FFAR4 agonist, increased granulosa cell proliferation and MAPK14 phosphorylation in a similar way to that observed with DHA treatment. However, TUG-891 treatment (1, 10 and 50 μM) showed no effect on progesterone or estradiol secretion. These data show that DHA stimulated proliferation and steroidogenesis of bovine

  1. Docosahexaenoic acid ester of phloridzin inhibit lipopolysaccharide-induced inflammation in THP-1 differentiated macrophages.

    Science.gov (United States)

    Sekhon-Loodu, Satvir; Ziaullah; Rupasinghe, H P Vasantha

    2015-03-01

    Phloridzin or phlorizin (PZ) is a predominant phenolic compound found in apple and also used in various natural health products. Phloridzin shows poor absorption and cellular uptake due to its hydrophilic nature. The aim was to investigate and compare the effect of docosahexaenoic acid (DHA) ester of PZ (PZ-DHA) and its parent compounds (phloridzin and DHA), phloretin (the aglycone of PZ) and cyclooxygenase inhibitory drugs (diclofenac and nimesulide) on production of pro-inflammatory biomarkers in inflammation-induced macrophages by lipopolysaccharide (LPS)-stimulation. Human THP-1 monocytes were seeded in 24-well plates (5×10(5)/well) and treated with phorbol 12-myristate 13-acetate (PMA, 0.1μg/mL) for 48h to induce macrophage differentiation. After 48h, the differentiated macrophages were washed with Hank's buffer and treated with various concentrations of test compounds for 4h, followed by the LPS-stimulation (18h). Pre-exposure of PZ-DHA ester was more effective in reducing tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2) protein levels compared to DHA and nimesulide. However, diclofenac was the most effective in reducing prostaglandin (PGE2) level by depicting a dose-dependent response. However, PZ-DHA ester and DHA were the most effective in inhibiting the activation of nuclear factor-kappa B (NF-κB) among other test compounds. Our results suggest that PZ-DHA ester might possess potential therapeutic activity to treat inflammation related disorders such as type 2 diabetes, asthma, atherosclerosis and inflammatory bowel disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Phospholipid class-specific brain enrichment in response to lysophosphatidylcholine docosahexaenoic acid infusion.

    Science.gov (United States)

    Chouinard-Watkins, Raphaël; Chen, Chuck T; Metherel, Adam H; Lacombe, R J Scott; Thies, Frank; Masoodi, Mojgan; Bazinet, Richard P

    2017-10-01

    Recent studies suggest that at least two pools of plasma docosahexaenoic acid (DHA) can supply the brain: non-esterified DHA (NE-DHA) and lysophosphatidylcholine (lysoPtdCho)-DHA. In contrast to NE-DHA, brain uptake of lysoPtdCho-DHA appears to be mediated by a specific transporter, but whether both forms of DHA supply undergo the same metabolic fate, particularly with regards to enrichment of specific phospholipid (PL) subclasses, remains to be determined. This study aimed to evaluate brain uptake of NE-DHA and lysoPtdCho-DHA into brain PL classes. Fifteen-week-old rats were infused intravenously with radiolabelled NE- 14 C-DHA or lysoPtdCho- 14 C-DHA (n=4/group) over five mins to achieve a steady-state plasma level. PLs were extracted from the brain and separated by thin layer chromatography and radioactivity was quantified by liquid scintillation counting. The net rate of entry of lysoPtdCho-DHA into the brain was between 59% and 86% lower than the net rate of entry of NE-DHA, depending on the PL class. The proportion of total PL radioactivity in the lysoPtdCho- 14 C-DHA group compared to the NE- 14 C-DHA group was significantly higher in choline glycerophospholipids (ChoGpl) (48% vs 28%, respectively) but lower in ethanolamine glycerophospholipids (EtnGpl) (32% vs 46%, respectively). In both groups, radioactivity was disproportionally high in phosphatidylinositol and ChoGpl but low in phosphatidylserine and EtnGpl compared to the corresponding DHA pool size. This suggests that DHA undergoes extensive PL remodeling after entry into the brain. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Prenatal Docosahexaenoic Acid Supplementation and Offspring Development at 18 Months: Randomized Controlled Trial

    Science.gov (United States)

    Ramakrishnan, Usha; Stinger, Amanda; DiGirolamo, Ann M.; Martorell, Reynaldo; Neufeld, Lynnette M.; Rivera, Juan A.; Schnaas, Lourdes; Stein, Aryeh D.; Wang, Meng

    2015-01-01

    Objective We evaluated the effects of prenatal docosahexaenoic acid (DHA) supplementation on offspring development at 18 months of age. Design Randomized placebo double-blind controlled trial. Settings Cuernavaca, Mexico. Participants and Methods We followed up offspring (n = 730; 75% of the birth cohort) of women in Mexico who participated in a trial of DHA supplementation during the latter half of pregnancy. We assessed the effect of the intervention on child development and the potential modifying effects of gravidity, gender, SES, and quality of the home environment. Interventions or Main Exposures 400 mg/day of algal DHA. Outcome Measures Child development at 18 months of age measured using the Spanish version of the Bayley Scales of Infant Development-II. We calculated standardized psychomotor and mental development indices, and behavior rating scale scores. Results Intent-to-treat differences (DHA-control) were: Psychomotor Developmental Index -0.90 (95% CI: -2.35, 0.56), Mental Developmental Index -0.26 (95% CI: -1.63, 1.10) and Behavior Rating Scale -0.01 (95% CI: -0.95, 0.94). Prenatal DHA intake attenuated the positive association between home environment and psychomotor development index observed in the control group (p for interaction = 0.03) suggesting potential benefits for children living in home environments characterized by reduced caregiver interactions and opportunities for early childhood stimulation. Conclusions Prenatal DHA supplementation in a population with low intakes of DHA had no effects on offspring development at 18 months of age although there may be some benefit for infants from poor quality home environments. Trial Registration Clinicaltrials.gov NCT00646360 PMID:26262896

  4. Crosstalk between Helicobacter pylori and gastric epithelial cells is impaired by docosahexaenoic acid.

    Directory of Open Access Journals (Sweden)

    Marta Correia

    Full Text Available H. pylori colonizes half of the world's population leading to gastritis, ulcers and gastric cancer. H. pylori strains resistant to antibiotics are increasing which raises the need for alternative therapeutic approaches. Docosahexaenoic acid (DHA has been shown to decrease H. pylori growth and its associated-inflammation through mechanisms poorly characterized. We aimed to explore DHA action on H. pylori-mediated inflammation and adhesion to gastric epithelial cells (AGS and also to identify bacterial structures affected by DHA. H. pylori growth and metabolism was assessed in liquid cultures. Bacterial adhesion to AGS cells was visualized by transmission electron microscopy and quantified by an Enzyme Linked Immunosorbent Assay. Inflammatory proteins were assessed by immunoblotting in infected AGS cells, previously treated with DHA. Bacterial total and outer membrane protein composition was analyzed by 2-dimensional gel electrophoresis. Concentrations of 100 µM of DHA decreased H. pylori growth, whereas concentrations higher than 250 µM irreversibly inhibited bacteria survival. DHA reduced ATP production and adhesion to AGS cells. AGS cells infected with DHA pre-treated H. pylori showed a 3-fold reduction in Interleukin-8 (IL-8 production and a decrease of COX2 and iNOS. 2D electrophoresis analysis revealed that DHA changed the expression of H. pylori outer membrane proteins associated with stress response and metabolism and modified bacterial lipopolysaccharide phenotype. As conclusions our results show that DHA anti-H. pylori effects are associated with changes of bacteria morphology and metabolism, and with alteration of outer membrane proteins composition, that ultimately reduce the adhesion of bacteria and the burden of H. pylori-related inflammation.

  5. Specific bile acid radioimmunoassays for separate determinations of unconjugated cholic acid, conjugated cholic acid and conjugated deoxycholic acid in serum and their clinical application

    International Nuclear Information System (INIS)

    Matern, S.; Gerok, W.

    1977-01-01

    Specific radioimmunoassays for separate determinations of serum unconjugated cholic, conjugated cholic and conjugated deoxycholic acids have been developed. Prior to the radioimmunoassay, extraction of serum bile acids was performed with Amberlite XAD-2. Unconjugated cholic acid was separated from glyco- and taurocholic acids by thin-layer chromatography. At 50% displacement of bound labeled glyco[ 3 H]cholic acid using antiserum obtained after immunization with cholic acid-bovine serum albumin-conjugate the cross-reactivity of taurocholic acid was 100%, cholic acid 80%, glycochenodeoxycholic acid 10%, chenodeoxycholic acid 7%, conjugated deoxycholic acid 3%, and conjugated lithocholic acid 3 H]cholic acid was linear on a logit-log plot from 5 to 80 pmol of unlabeled glycocholic acid. Fasting serum conjugated cholic acid in healthy subjects was 0.68 +- 0.34 μmol/l. Unconjugated cholic acid was determined by a solid phase radioimmunoassay using the cholic acid antibody chemically bound to Sepharose. The displacement curve of [ 3 H]cholic acid in the solid phase radioimmunoassay was linear on a logit-log plot from 5 to 200 pmol of unlabeled cholic acid. The coefficient of variation between samples was 5%. Fasting serum conjugated deoxycholic acid concentrations in 10 healthy subjects ranged from 0.18 to 0.92 μmol/l determined by a radioimmunoassay using antiserum obtained after immunization with deoxycholic acid-bovine serum albumin-conjugate. The clinical application of these bile acid radioimmunoassays is shown by an 'oral cholate tolerance test' as a sensitive indicator of liver function and by an 'oral cholyglycine tolerance test' as a useful test for bile acid absorption. (orig.) [de

  6. Effect of dietary arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid on survival, growth and pigmentation in larvae of common sole ( Solea solea L.)

    DEFF Research Database (Denmark)

    Lund, Ivar; Steenfeldt, Svend Jørgen; Hansen, B.W.

    2007-01-01

    Evidence confirms that polyunsaturated fatty acids (PUFAs), arachidonic acid (ARA), eicosapentaenoic acid (EPA) and docosahexaenoic acid, DHA are involved in growth as well in pigmentation of marine fish larvae. In the present study we examined the performance of common sole larvae reared...... on Artemia enriched with 10 formulated emulsions, differing in inclusions of ARA, EPA, and DHA. The specific growth rate of the sole larvae until late metamorphosis, 21 days after hatching (dah) was 20 to 27% d(-1). Even though the relative tissue essential fatty acid (EFA) concentrations significantly...... reflected dietary composition, neither standard growth nor larval survival were significantly related to the absolute concentrations of ARA, EPA and DHA or their ratios. This suggests low requirements for essential polyunsaturated fatty acids (PUFAs) in common sole. Malpigmentation was significantly related...

  7. Associations of obesity with triglycerides and C-reactive protein are attenuated in adults with high red blood cell eicosapentaenoic and docosahexaenoic acids

    Science.gov (United States)

    Background:N-3 fatty acids are associated with favorable, and obesity with unfavorable, concentrations of chronic disease risk biomarkers.Objective:We examined whether high eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid intakes, measured as percentages of total red blood cell (RBC) fatty acid...

  8. Docosahexaenoic acid (DHA) supplementation in pregnancy differentially modulates arachidonic acid and DHA status across FADS genotypes in pregnancy.

    Science.gov (United States)

    Scholtz, S A; Kerling, E H; Shaddy, D J; Li, S; Thodosoff, J M; Colombo, J; Carlson, S E

    2015-03-01

    Some FADS alleles are associated with lower DHA and ARA status assessed by the relative amount of arachidonic acid (ARA) and docosahexaenoic acid (DHA) in plasma and red blood cell (RBC) phospholipids (PL). We determined two FADS single nucleotide polymorphisms (SNPs) in a cohort of pregnant women and examined the relationship of FADS1rs174533 and FADS2rs174575 to DHA and ARA status before and after supplementation with 600mg per day of DHA. The 205 pregnant women studied were randomly assigned to placebo (mixed soy and corn oil) (n=96) or 600mg algal DHA (n=109) in 3 capsules per day for the last two trimesters of pregnancy. Women homozygous for the minor allele of FADS1rs174533 (but not FADS2rs174575) had lower DHA and ARA status at baseline. At delivery, minor allele homozygotes of FADS1rs174533 in the placebo group had lower RBC-DHA compared to major-allele carriers (P=0.031), while in the DHA-supplemented group, all genotypes had higher DHA status compared to baseline (P=0.001) and status did not differ by genotype (P=0.941). Surprisingly, DHA but not the placebo decreased ARA status of minor allele homozygotes of both FADS SNPs but not major allele homozygotes at delivery. Any physiological effects of changing the DHA to ARA ratio by increasing DHA intake appears to be greater in minor allele homozygotes of some FADS SNPs. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Occurrence of Conjugated Linolenic Acids in Purified Soybean Oil

    OpenAIRE

    Kinami, Tomohisa; Horii, Naoto; Narayan, Bhaskar; Arato, Shingo; Hosokawa, Masashi; Miyashita, Kazuo; Negishi, Hironori; Ikuina, Junichi; Noda, Ryuji; Shirasawa, Seiichi

    2007-01-01

    A high-performance liquid chromatographic (HPLC) method is described for the determination of conjugated linoleic acids (CLA) and conjugated linolenic acids (CLN). Methyl esters prepared from purified lipid fractions of soybean oil were analyzed using an HPLC system equipped with photodiode-array detector to detect peaks having maximum absorption around 233 and 275 nm. These peaks were concentrated by AgNO3-silicic acid column chromatography and reversed-phase HPLC. The structural analysis, o...

  10. 17β-estradiol increases liver and serum docosahexaenoic acid in mice fed varying levels of α-linolenic acid.

    Science.gov (United States)

    Mason, Julie K; Kharotia, Shikhil; Wiggins, Ashleigh K A; Kitson, Alex P; Chen, Jianmin; Bazinet, Richard P; Thompson, Lilian U

    2014-08-01

    Docosahexaenoic acid (DHA) is considered to be important for cardiac and brain function, and 17β-estradiol (E2) appears to increase the conversion of α-linolenic acid (ALA) into DHA. However, the effect of varying ALA intake on the positive effect of E2 on DHA synthesis is not known. Therefore, the objective of this study was to investigate the effects of E2 supplementation on tissue and serum fatty acids in mice fed a low-ALA corn oil-based diet (CO, providing 0.6 % fatty acids as ALA) or a high ALA flaxseed meal-based diet (FS, providing 11.2 % ALA). Ovariectomized mice were implanted with a slow-release E2 pellet at 3 weeks of age and half the mice had the pellet removed at 7 weeks of age. Mice were then randomized onto either the CO or FS diet. After 4 weeks, the DHA concentration was measured in serum, liver and brain. A significant main effect of E2 was found for liver and serum DHA, corresponding to 25 and 15 % higher DHA in livers of CO and FS rats, respectively, and 19 and 13 % in serum of CO and FS rats, respectively, compared to unsupplemented mice. There was no effect of E2 on brain DHA. E2 results in higher DHA in serum and liver, at both levels of dietary ALA investigated presently, suggesting that higher ALA intake may result in higher DHA in individuals with higher E2 status.

  11. The use of docosahexaenoic acid supplementation to ameliorate the hyperactivity of rat pups induced by in utero ethanol exposure

    OpenAIRE

    Furuya, Hiroyuki; Aikawa, Hiroyuki; Yoshida, Takahiko; Okazaki, Isao

    2000-01-01

    It has been demonstrated thatin utero ethanol (EtOH) exposure induces hyperactive behavior and learning disturbances in offspring. In order to investigate the effects of docosahexaenoic acid (DHA) on these neurobehavioral dysfunctions of rat pups induced byin utero EtOH exposure, pregnant Wistar rats were divided into four treatment groups depending on the type of oil added to the diet and drinking water as follows; (a) 5% safflower oil with tap water (TW/n-6), (b) 3% safflower oil and 2% DHA...

  12. Two-Stage Enzymatic Preparation of Eicosapentaenoic Acid (EPA) And Docosahexaenoic Acid (DHA) Enriched Fish Oil Triacylglycerols.

    Science.gov (United States)

    Zhang, Zhen; Liu, Fang; Ma, Xiang; Huang, Huihua; Wang, Yong

    2018-01-10

    Fish oil products in the form of triacylglycerols generally have relatively low contents of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and so it is of potential research and industrial interest to enrich the related contents in commercial products. Thereby an economical and efficient two-stage preparation of EPA and DHA enriched fish oil triacylglycerols is proposed in this study. The first stage was the partial hydrolysis of fish oil by only 0.2 wt.‰ AY "Amano" 400SD which led to increases of EPA and DHA contents in acylglycerols from 19.30 and 13.09 wt % to 25.95 and 22.06 wt %, respectively. Subsequently, products of the first stage were subjected to transesterification with EPA and DHA enriched fatty acid ethyl esters (EDEE) as the second stage to afford EPA and DHA enriched fish oil triacylglycerols by using as low as 2 wt % Novozyme 435. EDEEs prepared from fish oil ethyl ester, and recycled DHA and EPA, respectively, were applied in this stage. Final products prepared with two different sources of EDEEs were composed of 97.62 and 95.92 wt % of triacylglycerols, respectively, with EPA and DHA contents of 28.20 and 21.41 wt % for the former and 25.61 and 17.40 wt % for the latter. Results not only demonstrate this two-stage process's capability and industrial value for enriching EPA and DHA in fish oil products, but also offer new opportunities for the development of fortified fish oil products.

  13. Effects of dietary gamma-linolenic acid and docosahexaenoic acid with paclitaxel on the treatment of mice mammary carcinoma

    Directory of Open Access Journals (Sweden)

    Kamran Rakhshan

    2013-08-01

    Full Text Available Background: Breast cancer is one of the most important causes of death in women. One of the various gene expression involved in breast cancer is human epidermal growth factor receptor 2 (HER2/neu gene expression increases. Factors of dietary affect on regulation of hormone secretion and the rate of breast cancer. One of these factors is amount and type of fats in diet. Gamma-linolenic acid (GLA and Docosah-exaenoic acid (DHA are members of poly unsaturated fatty acids. In this study, effects of dietary GLA and DHA alone or together with paclitaxel on treatment of mice mammary carcinoma has been evaluated.Methods: Thirty female balb/c mice were divided in six groups randomly. Carcinoma-tous mass induced by tumor implantation method. Spontaneous breast adenocarcinoma of mice were used as tumor stock. The tumors of these mice were removed aseptically, dissected into 0.5 cm3 pieces. These pieces were transplanted subcutaneously into their right flank. GLA and DHA added to the mice diet two week prior to tumor implanta-tion. At the end of intervention, tumors were removed and HER2 gene expression was measured. The weight of animal and tumor volume measured weekly.Results: It was not significant change in the weight of animals that consumed DHA and DHA with taxol. Tumor volume in those groups that received corn oil with taxol (P<0.01, DHA (P<0.05 and DHA with taxol (P<0.001 showed significant decrease in comparison with control group. HER2 gene expression in DHA with taxol decreased significantly in comparison with control group (P<0.05.Conclusion: Consumption of DHA oil with taxol causes decrease the volume of carcin-oma mass. The future studies with large number of sample is needed to support this finding.

  14. Dietary intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in children - a workshop report

    NARCIS (Netherlands)

    Koletzko, B.; Uauy, R.; Palou, A.; Kok, F.J.; Hornstra, G.; Eilander, A.; Moretti, D.; Osendarp, S.J.M.; Zock, P.L.; Innis, S.

    2010-01-01

    There is controversy whether children should have a dietary supply of preformed long-chain polyunsaturated n-3 fatty acids EPA and DHA. The aims of the workshop were to review evidence for a possible benefit of a preformed EPA and/or DHA supply, of data required to set desirable intakes for children

  15. Antibacterial activities of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) against planktonic and biofilm growing Streptococcus mutans.

    Science.gov (United States)

    Sun, Mengjun; Dong, Jiachen; Xia, Yiru; Shu, Rong

    2017-06-01

    The aim of this study was to evaluate the potential antibacterial activities of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) against planktonic and biofilm modes of Streptococcus mutans (S. mutans). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined. The effects on planktonic growth and biofilm metabolic activity were evaluated by growth curve determination and MTT assay, respectively. Then, colony forming unit (CFU) counting, scanning electron microscopy (SEM) and real-time PCR were performed to further investigate the actions of DHA and EPA on exponential phase-S. mutans. Confocal laser scanning microscopy (CLSM) was used to detect the influences on mature biofilms. The MICs of DHA and EPA against S. mutans were 100 μM and 50 μM, respectively; the MBC of both compounds was 100 μM. In the presence of 12.5 μM-100 μM DHA or EPA, the planktonic growth and biofilm metabolic activity were reduced in varying degrees. For exponential-phase S. mutans, the viable counts, the bacterial membranes and the biofilm-associated gene expression were damaged by 100 μM DHA or EPA treatment. For 1-day-old biofilms, the thickness was decreased and the proportion of membrane-damaged bacteria was increased in the presence of 100 μM DHA or EPA. These results indicated that, DHA and EPA possessed antibacterial activities against planktonic and biofilm growing S. mutans. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Cyclooxygenase-2 induction in macrophages is modulated by docosahexaenoic acid via interactions with free fatty acid receptor 4 (FFA4).

    Science.gov (United States)

    Li, Xinzhi; Yu, Ying; Funk, Colin D

    2013-12-01

    Cyclooxygenase-2 (COX-2)-derived prostaglandins are implicated in numerous inflammatory disorders. The purpose of these studies was to examine previously unexplored interactions between COX-2 induction and docosahexaenoic acid (DHA) via the free fatty acid receptor 4 (FFA4) signaling pathway in murine RAW 264.7 cells and peritoneal macrophages challenged with lipopolysaccharide (LPS). DHA dose (IC50=18 μM)- and time-dependently reduced COX-2 expression, without affecting COX-1. DHA (25 μM for 24 h) decreased LPS-induced prostaglandin E2 (PGE2) synthesis by 81%, primarily through reducing COX-2 (60%), as well as down-regulating microsomal prostaglandin E synthase-1 (46%), but independently of peroxisome proliferator-activated receptors. FFA4 knockdown abrogated DHA effects on COX-2 induction, PGE2 production, and interleukin 6 (IL-6) gene expression. In the presence of inhibitors of eicosanoid metabolism via COX-2, 12/15-lipoxygenase and CYP450s (rofecoxib (1 μM), PD146176 (2 μM), or MS-PPOH (20 μM)), DHA was still effective in attenuating COX-2 induction. Moreover, Toll-like receptor 4 signaling via Akt/JNK phosphorylation and p65 nuclear translocation was repressed by DHA-activated FFA4 coupling with β-arrestin 2, which was reversed by FFA4 knockdown. These data support DHA modulation of COX-2 expression and activity, in part, via FFA4, which provides a new mechanistic explanation for some of the anti-inflammatory effects of DHA.

  17. Eicosapentaenoic acid and docosahexaenoic acid have distinct membrane locations and lipid interactions as determined by X-ray diffraction.

    Science.gov (United States)

    Sherratt, Samuel C R; Mason, R Preston

    2018-01-31

    Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) differentially influence lipid oxidation, signal transduction, fluidity, and cholesterol domain formation, potentially due in part to distinct membrane interactions. We used small angle X-ray diffraction to evaluate the EPA and DHA effects on membrane structure. Membrane vesicles composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and cholesterol (C) (0.3C:POPC mole ratio) were prepared and treated with vehicle, EPA, or DHA (1:10 mol ratio to POPC). Electron density profiles generated from the diffraction data showed that EPA increased membrane hydrocarbon core electron density over a broad area, up to ± 20 Å from the membrane center, indicating an energetically favorable extended orientation for EPA likely stabilized by van der Waals interactions. By contrast, DHA increased electron density in the phospholipid head group region starting at ± 12 Å from the membrane center, presumably due to DHA-surface interactions, with coincident reduction in electron density in the membrane hydrocarbon core centered ± 7-9 Å from the membrane center. The membrane width (d-space) decreased by 5 Å in the presence of vehicle as the temperature increased from 10 °C to 30 °C due to increased acyl chain trans-gauche isomerizations, which was unaffected by addition of EPA or DHA. The influence of DHA on membrane structure was modulated by temperature changes while the interactions of EPA were unaffected. The contrasting EPA and DHA effects on membrane structure indicate distinct molecular locations and orientations that may contribute to observed differences in biological activity. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Docosahexaenoic acid (DHA, essentiality and requirements: why and how to provide supplementation

    Directory of Open Access Journals (Sweden)

    Nieto, Susana

    2006-06-01

    Full Text Available Lipids comprize from 50-60% of the structural matter of the brain and docosahexaenoic acid (C22:6, DHA is the most  important omega-3 long-chain polyunsaturated fatty acid in the brain phospholipids comprizing 25% of the total fatty acids of the grey matter. The majority of the DHA present in the human brain is incorporated during the brain growth spurt which starts at week 26 of gestation and imposes a high demand for the fatty acid until about 2 years of age. DHA is required during brain development when neuronal and glial differentiation and migration, and active myelination and synaptogenesis take place. The fatty acid must be incorporated into the brain lipids as preformed DHA because less than 5% of its precursor (alpha linolenic acid, LNA is converted to DHA. The human foetus has a limited ability to synthesize DHA from LNA, and therefore it must be largely supplied from maternal sources. Maternal DHA available for foetal nutrition can be provided from three main sources: adipose tissue, which is the main reservoir for the fatty acid; through biosynthesis from the precursor LNA, which occurs mainly in the liver; and as preformed DHA from dietary sources. In the postnatal period DHA is provided by the mother to the newborn through milk secretion. Western nutrition provides low LNA and DHA and Expert Nutrition Committees suggest that mothers should receive DHA supplementation during pregnancy and lactation. At present DHA supplementation can be provided from different sources: as purified free DHA, as an ethyl ester derivative, extracted from single-cell algae oils, from egg yolk phospholipids, or in the form of sn-2 DHA monoacylglycerol. In this review we revise and discuss the evidence of DHA requirements for the newborn, the need for maternal supplementation during pregnancy and nursing, and the alternatives at present for providing DHA supplementation.Los lípidos comprenden entre el 50-60% de la estructura del cerebro, y el

  19. Utilization of High-Fructose Corn Syrup for Biomass Production Containing High Levels of Docosahexaenoic Acid by a Newly Isolated Aurantiochytrium sp. YLH70.

    Science.gov (United States)

    Yu, Xin-Jun; Yu, Zhi-Qiang; Liu, Ying-Liang; Sun, Jie; Zheng, Jian-Yong; Wang, Zhao

    2015-11-01

    High-fructose corn syrup (HFCS) is an agro-source product and has been the most commonly used substitute for sugar as sweetener in food industry due to its low price and high solution property. In this study, the F55 HFCS, rich in fructose and glucose, was first tested for biomass and docosahexaenoic acid productions as a mixed carbon source by a newly isolated Aurantiochytrium sp.YLH70. After the compositions of the HFCS media were optimized, the results showed that the HFCS with additions of metal ion and vitamin at low concentrations was suitable for biomass and docosahexaenoic acid productions and the metal ion and sea salt had the most significant effects on biomass production. During the 5-l fed-batch fermentation, total HFCS containing 180 g l(-1) reducing sugar was consumed and yields of biomass, lipid, and DHA could reach 78.5, 51, and 20.1 g l(-1), respectively, at 114 h. Meanwhile, the daily productivity and the reducing sugar conversion yield for docosahexaenoic acid were up to 4.23 g l(-1)day(-1) and 0.11 g g(-1). The fatty acid profile of Aurantiochytrium sp.YLH70 showed that 46.4% of total fatty acid was docosahexaenoic acid, suggesting that Aurantiochytrium sp.YLH70 was a promising DHA producer.

  20. Oral administration of eicosapentaenoic acid or docosahexaenoic acid modifies cardiac function and ameliorates congestive heart failure in male rats.

    Science.gov (United States)

    Yamanushi, Tomoko T; Kabuto, Hideaki; Hirakawa, Eiichiro; Janjua, Najma; Takayama, Fusako; Mankura, Mitsumasa

    2014-04-01

    This study assessed the effects of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) on normal cardiac function (part 1) and congestive heart failure (CHF) (part 2) through electrocardiogram analysis and determination of EPA, DHA, and arachidonic acid (AA) concentrations in rat hearts. In part 2, pathologic assessments were also performed. For part 1 of this study, 4-wk-old male rats were divided into a control group and 2 experimental groups. The rats daily were orally administered (1 g/kg body weight) saline, EPA-ethyl ester (EPA-Et; E group), or DHA-ethyl ester (DHA-Et; D group), respectively, for 28 d. ECGs revealed that QT intervals were significantly shorter for groups E and D compared with the control group (P ≤ 0.05). Relative to the control group, the concentration of EPA was higher in the E group and concentrations of EPA and DHA were higher in the D group, although AA concentrations were lower (P ≤ 0.05). In part 2, CHF was produced by subcutaneous injection of monocrotaline into 5-wk-old rats. At 3 d before monocrotaline injection, rats were administered either saline, EPA-Et, or DHA-Et as mentioned above and then killed at 21 d. The study groups were as follows: normal + saline (control), CHF + saline (H group), CHF + EPA-Et (HE group), and CHF + DHA-Et (HD group). QT intervals were significantly shorter (P ≤ 0.05) in the control and HD groups compared with the H and HE groups. Relative to the H group, concentrations of EPA were higher in the HE group and those of DHA were higher in the control and HD groups (P ≤ 0.05). There was less mononuclear cell infiltration in the myocytes of the HD group than in the H group (P = 0.06). The right ventricles in the H, HE, and HD groups showed significantly increased weights (P ≤ 0.05) compared with controls. The administration of EPA-Et or DHA-Et may affect cardiac function by modification of heart fatty acid composition, and the administration of DHA-Et may ameliorate CHF.

  1. Feeding nitrate and docosahexaenoic acid affects enteric methane production and milk fatty acid composition in lactating dairy cows.

    Science.gov (United States)

    Klop, G; Hatew, B; Bannink, A; Dijkstra, J

    2016-02-01

    An experiment was conducted to study potential interaction between the effects of feeding nitrate and docosahexaenoic acid (DHA; C22:6 n-3) on enteric CH4 production and performance of lactating dairy cows. Twenty-eight lactating Holstein dairy cows were grouped into 7 blocks of 4 cows. Within blocks, cows were randomly assigned to 1 of 4 treatments: control (CON; urea as alternative nonprotein N source to nitrate), NO3 [21 g of nitrate/kg of dry matter (DM)], DHA (3 g of DHA/kg of DM and urea as alternative nonprotein N source to nitrate), or NO3 + DHA (21 g of nitrate/kg of DM and 3 g of DHA/kg of DM, respectively). Cows were fed a total mixed ration consisting of 21% grass silage, 49% corn silage, and 30% concentrates on a DM basis. Feed additives were included in the concentrates. Cows assigned to a treatment including nitrate were gradually adapted to the treatment dose of nitrate over a period of 21 d during which no DHA was fed. The experimental period lasted 17 d, and CH4 production was measured during the last 5d in climate respiration chambers. Cows produced on average 363, 263, 369, and 298 g of CH4/d on CON, NO3, DHA, and NO3 + DHA treatments, respectively, and a tendency for a nitrate × DHA interaction effect was found where the CH4-mitigating effect of nitrate decreased when combined with DHA. This tendency was not obtained for CH4 production relative to dry matter intake (DMI) or to fat- and protein corrected milk (FPCM). The NO3 treatment decreased CH4 production irrespective of the unit in which it was expressed, whereas DHA did not affect CH4 production per kilogram of DMI, but resulted in a higher CH4 production per kilogram of fat- and protein-corrected milk (FPCM) production. The FPCM production (27.9, 24.7, 24.2, and 23. 8 kg/d for CON, NO3, DHA, and NO3 + DHA, respectively) was lower for DHA-fed cows because of decreased milk fat concentration. The proportion of saturated fatty acids in milk fat was decreased by DHA, and the proportion of

  2. Docosahexaenoic acid (DHA, an essential fatty acid for the proper functioning of neuronal cells: their role in mood disorders

    Directory of Open Access Journals (Sweden)

    2009-06-01

    Full Text Available The brain and the nervous system are tissues with high contents of two polyunsaturated fatty acids: arachidonic acid (20:4, omega-6, AA and docosahexaenoic acid (22:6, omega-3, DHA. Despite their abundance in these tissues, AA and DHA cannot be re-synthesized in mammals. However, the concentration of these fatty acids can be modulated by dietary intake. AA and DHA must be provided by the diet as such (preformed or through the respective omega-6 and omega-3 precursors from vegetable origin. Linoleic acid, the precursor of AA is very abundant in the western diet and therefore the formation of AA from linoleic acid is not restrictive. On the other hand, alpha linolenic acid, the precursor of DHA is less available in our diet and preformed DHA is highly restrictive in some populations. During the last period of gestation and during the early post natal period, neurodevelopment occurs exceptionally quickly, and significant amounts of omega-6 and omega-3 polyunsaturated fatty acids, especially DHA, are critical to allow neurite outgrowth and the proper brain and retina development and function. In this review various functions of DHA in the nervous system, its metabolism into phospholipids, and its involvement in different neurological and mood disorders, such as Alzheimer’s disease, depression, and others are revised.

    El cerebro y el sistema nervioso son tejidos con un alto contenido de dos ácidos grasos poliinsaturados: el ácido araquidónico (20:4, omega-6, AA y el ácido docosahexaenoico (22:6, omega-3, DHA. A pesar de la abundancia de estos ácidos grasos en dichos tejidos los mamíferos no los pueden sintetizar de novo. Sin embargo, la concentración de estos ácidos grasos puede ser modificada por la dieta. El AA y el DHA pueden ser aportados por la dieta como tales (preformados o a partir de los respectivos precursores de origen vegetal. El ácido linoleico, precursor del AA es muy abundante en la dieta occidental, por lo cual la

  3. In silico Screening and Evaluation of the Anticonvulsant Activity of Docosahexaenoic Acid-Like Molecules in Experimental Models of Seizures.

    Science.gov (United States)

    Gharibi Loron, Ali; Sardari, Soroush; Narenjkar, Jamshid; Sayyah, Mohammad

    2017-01-01

    Resistance to antiepileptic drugs and the intolerability in 20-30% of the patients raises demand for developing new drugs with improved efficacy and safety. Acceptable anticonvulsant activity, good tolerability, and inexpensiveness of docosahexaenoic acid (DHA) make it as a good candidate for designing and development of the new anticonvulsant medications. Ten DHA-based molecules were screened based on in silico screening of DHA-like molecules by root-mean-square deviation of atomic positions, the biological activity score of Professional Association for SQL Server, and structural requirements suggested by pharmacophore design. Anticonvulsant activity was tested against clonic seizures induced by pentylenetetrazole (PTZ, 60 mg/kg, i.p.) and tonic seizures induced by maximal electroshock (MES, 50 mA, 50 Hz, 1 ms duration) by intracerebroventricular (i.c.v.) injection of the screened compounds to mice. Among screened compounds, 4-Phenylbutyric acid, 4-Biphenylacetic acid, phenylacetic acid, and 2-Phenylbutyric acid showed significant protective activity in pentylenetetrazole test with ED50 values of 4, 5, 78, and 70 mM, respectively. In MES test, shikimic acid and 4-tert-Butylcyclo-hexanecarboxylic acid showed significant activity with ED50 values 29 and 637 mM, respectively. Effective compounds had no mortality in mice up to the maximum i.c.v. injectable dose of 1 mM. Common electrochemical features and three-dimensional spatial structures of the effective compounds suggest the involvement of the anticonvulsant mechanisms similar to the parent compound DHA.

  4. Maternal Docosahexaenoic Acid Intake Levels during Pregnancy and Infant Performance on a Novel Object Search Task at 22 Months

    Science.gov (United States)

    Rees, Alison; Sirois, Sylvain; Wearden, Alison

    2014-01-01

    This study investigated maternal prenatal docosahexaenoic acid (DHA) intake and infant cognitive development at 22 months. Estimates for second- and third-trimester maternal DHA intake levels were obtained using a comprehensive Food Frequency Questionnaire. Infants (n = 67) were assessed at 22 months on a novel object search task. Mothers'…

  5. High contents of both docosahexaenoic and arachidonic acids in milk of women consuming fish from lake Kitangiri (Tanzania) : targets for infant formulae close to our ancient diet?

    NARCIS (Netherlands)

    Kuipers, RS; Fokkema, MR; Smit, EN; van der Meulen, J; Boersma, ER; Muskiet, FAJ

    Current recommendations for arachidonic (AA) and docosahexaenoic (DHA) acids in infant formulae are based on milk of Western mothers. Validity may be questioned in view of the profound dietary changes in the past 100 years, as opposed to our slowly adapting genome. Hominin evolution occurred in the

  6. Production of high docosahexaenoic acid by Schizochytrium sp. using low-cost raw materials from food industry.

    Science.gov (United States)

    Song, Xiaojin; Zang, Xiaonan; Zhang, Xuecheng

    2015-01-01

    The low-cost substrates from food industry, including maize starch hydrolysate and soybean meal hydrolysate, were used to produce docosahexaenoic acid (DHA) by Schizochytrium limacinum OUC88. Glucose derived from maize starch hydrolysate was used as the carbon source and soybean meal hydrolysate as the nitrogen sources. In 10L bioreactor fermentation, by using the soybean meal hydrolysate as the main nitrogen source, the biomass of Schizochytrium limacinum OUC88 reached 85.27 g L(-1), and the yields of DHA was 20.7g L(-1). As a comparison, when yeast extract was used as the main nitrogen source, the yields of biomass and DHA were 68.93 g L(-1) and 13.3 g L(-1), respectively. From the results of this study, these hydrolysates can provide all the nutrients required for high-density cultivation of S. limacinum OUC88 and DHA production, that will improve the economical and competitive efficiency of commercial DHA production.

  7. Interaction of fructose with other medium components to affect bioproduction of docosahexaenoic acid (DHA) by Aurantiochytrium sp. SW1

    Science.gov (United States)

    Manikan, Vidyah; Kalil, Mohd. Sahaid; Shuib, Shuwahida; Hamid, Aidil Abdul

    2018-04-01

    Thraustochytrids are a group of marine fungus-like microheterotrophs of which some can accumulate considerable amounts of the high valued omega-3 oil, docosahexaenoic acid (DHA). In this study, a local thraustochytrid isolate, Aurantiochytrium sp. SW1, was cultivated in a medium containing fructose as the major carbon source. The effects of this carbon source in interaction with yeast extract, monosodium glutamate (MSG) and sea salt were studied using a software-based two level full factorial design. Results showed that fructose as a single factor, has significant positive effect on the volumetric DHA content of SW1. Similarly, its interaction with yeast extract has profound positive effect. However, interactions of fructose with MSG and sea salt were significant negative effects. These results indicate that manipulation of the concentration of fructose in the culture medium may serve as a simple and useful strategy to help achieve preferred amount of DHA.

  8. AceDoPC, a structured phospholipid to target the brain with docosahexaenoic acid

    Directory of Open Access Journals (Sweden)

    Lagarde Michel

    2016-01-01

    Full Text Available AceDoPC® is a structured phospholipid or acetyl-LysoPC-DHA made to prevent docosahexaenoic acyl migrating from the sn-2 to sn-1 position of the phospholipid, however keeping the main physical-chemical properties of LysoPC-DHA. As previously shown for LysoPC-DHA, AceDoPC® allows DHA crossing a re-constituted blood-brain barrier with higher efficiency than non-esterified DHA or PC-DHA. When injected to blood of rats, AceDoPC® is processed within the brain to deliver DHA to phosphatidyl-choline and -ethanolamine. When injected to rats following the induction of an ischemic stroke, AceDoPC® prevents the extension of brain lesions more efficiently than DHA. Overall, these properties make AceDoPC® a promising phospholipid carrier of DHA to the brain.

  9. Increased Erythrocyte Eicosapentaenoic Acid and Docosahexaenoic Acid Are Associated With Improved Attention and Behavior in Children With ADHD in a Randomized Controlled Three-Way Crossover Trial.

    Science.gov (United States)

    Milte, Catherine M; Parletta, Natalie; Buckley, Jonathan D; Coates, Alison M; Young, Ross M; Howe, Peter R C

    2015-11-01

    To investigate effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on attention, literacy, and behavior in children with ADHD. Ninety children were randomized to consume supplements high in EPA, DHA, or linoleic acid (control) for 4 months each in a crossover design. Erythrocyte fatty acids, attention, cognition, literacy, and Conners' Parent Rating Scales (CPRS) were measured at 0, 4, 8, 12 months. Fifty-three children completed the treatment. Outcome measures showed no significant differences between the three treatments. However, in children with blood samples (n = 76-46), increased erythrocyte EPA + DHA was associated with improved spelling (r = .365, p attention (r = -.540, p improve behavior, attention, and literacy in children with ADHD. © The Author(s) 2013.

  10. Intake of total omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid and risk of coronary heart disease in the Spanish EPIC cohort study.

    Science.gov (United States)

    Amiano, P; Machón, M; Dorronsoro, M; Chirlaque, M Dolores; Barricarte, A; Sánchez, M-J; Navarro, C; Huerta, J M; Molina-Montes, E; Sánchez-Cantalejo, E; Urtizberea, M; Arriola, L; Larrañaga, N; Ardanaz, E; Quirós, J R; Moreno-Iribas, C; González, C A

    2014-03-01

    The evidence about the benefits of omega-3 fatty acid intake on coronary heart disease (CHD) is not consistent. We thus aimed to assess the relation between dietary intake of total omega-3 fatty acids (from plant and marine foods) and marine polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on the risk of CHD in the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 41,091 men and women aged 20-69 years, recruited from 1992 to 1996 and followed-up until December 2004. Omega-3 fatty acid intake was estimated from a validated dietary questionnaire. Only participants with definite incident CHD event were considered as cases. Cox regression models were used to assess the association between the intake of total omega-3 fatty acids, EPA or DHA and CHD. A total of 609 participants (79% men) had a definite CHD event. Mean intakes of total omega-3 fatty acids, EPA and DHA were very similar in the cases and in the cohort, both in men and women. In the multivariate adjusted model, omega-3 fatty acids, EPA and DHA were not related to incident CHD in either men or women. The hazard ratios (HR) for omega-3 were 1.23 in men (95% CI 0.94-15.9, p = 0.20); and 0.77 in women (95% CI 0.46-1.30, p = 0.76). In the Spanish EPIC cohort, with a relatively high intake of fish, no association was found between EPA, DHA and total omega-3 fatty acid intake and risk of CHD. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. The effect of conjugated linoleic acid on the fatty acid composition of ...

    African Journals Online (AJOL)

    rahim aydin

    Dietary conjugated linoleic acid (CLA) was reported to increase the levels of saturated fatty ... Hence, the objective of this study was to determine the effects of dietary CLA on the fatty acid ..... silver ion-high performance liquid chromatography.

  12. Quantitation of alpha-linolenic acid elongation to eicosapentaenoic and docosahexaenoic acid as affected by the ratio of n6/n3 fatty acids

    Directory of Open Access Journals (Sweden)

    Somoza Veronika

    2009-02-01

    Full Text Available Abstract Background Conversion of linoleic acid (LA and alpha-linolenic acid (ALA to their higher chain homologues in humans depends on the ratio of ingested n6 and n3 fatty acids. Design and methods In order to determine the most effective ratio with regard to the conversion of ALA to eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA, human hepatoma cells were incubated with varying ratios of [13C] labeled linoleic acid ([13C]LA- and alpha-linolenic acid ([13C]ALA-methylesters. Regulative cellular signal transduction pathways involved were studied by determinations of transcript levels of the genes encoding delta-5 desaturase (D5D and delta-6 desaturase (D6D, peroxisome proliferator-activated receptor alpha (PPARα and sterol regulatory element binding protein 1c (SREBP-1c. Mitogen-activated protein kinase kinase 1 (MEK1 and mitogen-activated protein kinase kinase kinase 1 (MEKK1 were also examined. Results Maximum conversion was observed in cells incubated with the mixture of [13C]LA/[13C]ALA at a ratio of 1:1, where 0.7% and 17% of the recovered [13C]ALA was converted to DHA and EPA, respectively. Furthermore, differential regulation of enzymes involved in the conversion at the transcript level, dependent on the ratio of administered n6 to n3 fatty acids in human hepatocytes was demonstrated. Conclusion Formation of EPA and DHA was highest at an administered LA/ALA ratio of 1:1, although gene expression of PPARα, SREBP-1c and D5D involved in ALA elongation were higher in the presence of ALA solely. Also, our findings suggest that a diet-induced enhancement of the cell membrane content of highly unsaturated fatty acids is only possible up to a certain level.

  13. Treatment of an adrenomyeloneuropathy patient with Lorenzo's oil and supplementation with docosahexaenoic acid-A case report

    Directory of Open Access Journals (Sweden)

    Bergh Jacobus J

    2011-08-01

    Full Text Available Abstract This is a case report of adrenomyeloneuropathy (AMN, the adult variant of adrenoleukodystryphy (ALD. The diagnoses in the patient, aged 34, was confirmed via increased serum very long chain fatty acid concentration (VLCFA. Treatment started with the cholesterol lowering drug, atorvastatin, followed by add-on therapy with Lorenzo's oil (LO and finally supplementation with docosahexaenoic acid (DHA. The magnetic resonance imaging (MRI scan of the AMN patient before DHA treatment, already showed abnormal white matter in the brain. Although the MRI showed no neurological improvement after 6 months of DHA treatment, no selective progression of demyelination was detected in the AMN patient. Contrary to what was expected, LO failed to sustain or normalize the VLCFA levels or improve clinical symptoms. It was however, shown that DHA supplementation in addition to LO, increased DHA levels in both plasma and red blood cells (RBC. Additionally, the study showed evidence that the elongase activity in the elongation of eicosapentaenoic acid (EPA to docosapentaenoic acid (DPA might have been significantly compromised, due to the increased DHA levels.

  14. NR4A orphan nuclear receptors influence retinoic acid and docosahexaenoic acid signaling via up-regulation of fatty acid binding protein 5

    International Nuclear Information System (INIS)

    Volakakis, Nikolaos; Joodmardi, Eliza; Perlmann, Thomas

    2009-01-01

    The orphan nuclear receptor (NR) Nurr1 is expressed in the developing and adult nervous system and is also induced as an immediate early gene in a variety of cell types. In silico analysis of human promoters identified fatty acid binding protein 5 (FABP5), a protein shown to enhance retinoic acid-mediated PPARβ/δ signaling, as a potential Nurr1 target gene. Nurr1 has previously been implicated in retinoid signaling via its heterodimerization partner RXR. Since NRs are commonly involved in cross-regulatory control we decided to further investigate the regulatory relationship between Nurr1 and FABP5. FABP5 expression was up-regulated by Nurr1 and other NR4A NRs in HEK293 cells, and Nurr1 was shown to activate and bind to the FABP5 promoter, supporting that FABP5 is a direct downstream target of NR4A NRs. We also show that the RXR ligand docosahexaenoic acid (DHA) can induce nuclear translocation of FABP5. Moreover, via up-regulation of FABP5 Nurr1 can enhance retinoic acid-induced signaling of PPARβ/δ and DHA-induced activation of RXR. We also found that other members of the NR4A orphan NRs can up-regulate FABP5. Thus, our findings suggest that NR4A orphan NRs can influence signaling events of other NRs via control of FABP5 expression levels.

  15. NR4A orphan nuclear receptors influence retinoic acid and docosahexaenoic acid signaling via up-regulation of fatty acid binding protein 5

    Energy Technology Data Exchange (ETDEWEB)

    Volakakis, Nikolaos; Joodmardi, Eliza [Ludwig Institute for Cancer Research Ltd., Box 240, S-17177 Stockholm (Sweden); Perlmann, Thomas, E-mail: thomas.perlmann@licr.ki.se [Ludwig Institute for Cancer Research Ltd., Box 240, S-17177 Stockholm (Sweden); The Department of Cell and Molecular Biology, Karolinska Institute, S-17177 Stockholm (Sweden)

    2009-12-25

    The orphan nuclear receptor (NR) Nurr1 is expressed in the developing and adult nervous system and is also induced as an immediate early gene in a variety of cell types. In silico analysis of human promoters identified fatty acid binding protein 5 (FABP5), a protein shown to enhance retinoic acid-mediated PPAR{beta}/{delta} signaling, as a potential Nurr1 target gene. Nurr1 has previously been implicated in retinoid signaling via its heterodimerization partner RXR. Since NRs are commonly involved in cross-regulatory control we decided to further investigate the regulatory relationship between Nurr1 and FABP5. FABP5 expression was up-regulated by Nurr1 and other NR4A NRs in HEK293 cells, and Nurr1 was shown to activate and bind to the FABP5 promoter, supporting that FABP5 is a direct downstream target of NR4A NRs. We also show that the RXR ligand docosahexaenoic acid (DHA) can induce nuclear translocation of FABP5. Moreover, via up-regulation of FABP5 Nurr1 can enhance retinoic acid-induced signaling of PPAR{beta}/{delta} and DHA-induced activation of RXR. We also found that other members of the NR4A orphan NRs can up-regulate FABP5. Thus, our findings suggest that NR4A orphan NRs can influence signaling events of other NRs via control of FABP5 expression levels.

  16. Arachidonic acid/docosahexaenoic acid-supplemented diet in early life reduces body weight gain, plasma lipids, and adiposity in later life in ApoE*3 Leiden mice

    NARCIS (Netherlands)

    Wielinga, P.Y.; Harthoorn, L.F.; Verschuren, L.; Schoemaker, M.H.; Jouni, Z.E.; Tol, E.A.F. van; Kleemann, R.; Kooistra, T.

    2012-01-01

    Scope: This study addresses whether early life arachidonic acid (ARA)/docosahexaenoic acid (DHA) supplementation or eicosapentaenoic acid (EPA)/DHA (Omacor) supplementation affects body weight gain, lipid metabolism, and adipose tissue quantity and quality in later life in ApoE*3Leiden-transgenic

  17. Eicosapentaenoic acid and docosahexaenoic acid in whole blood are differentially and sex-specifically associated with cardiometabolic risk markers in 8-11-year-old danish children

    DEFF Research Database (Denmark)

    Damsgaard, Camilla T.; Eidner, Maj B.; Stark, Ken D.

    2014-01-01

    ) investigated associations between EPA and DHA in whole blood and early cardiometabolic risk markers in 713 children aged 8-11 years and 2) explored potential mediation through waist circumference and physical activity and potential dietary confounding. We collected data on parental education, pubertal stage, 7......n-3 long-chain polyunsaturated fatty acids improve cardiovascular risk markers in adults. These effects may differ between eicosapentaenoic acid (EPA, 20∶5n-3) and docosahexaenoic acid (DHA, 22∶6n-3), but we lack evidence in children. Using baseline data from the OPUS School Meal Study we 1......-day dietary records, physical activity by accelerometry and measured anthropometry, blood pressure, and heart rate. Blood samples were analyzed for whole blood fatty acid composition, cholesterols, triacylglycerol, insulin resistance by the homeostatic model of assessment (HOMA-IR), and inflammatory...

  18. Incorporation of conjugated linoleic acid (CLA and α-linolenic acid (LNA in pacu fillets

    Directory of Open Access Journals (Sweden)

    Deoclécio José Barilli

    2014-03-01

    Full Text Available The objective of this study was to evaluate the incorporation of conjugated linoleic acid and α-linolenic acid in fillets of pacu fish raised in net cages and fed diets enriched with these acids. The fish were fed for 49 days, and at the end of this period the fatty acid content in the fillets was determined by gas chromatography. Concentrations of α-linolenic acid, eicosapentaenoic acid, and the total omega-3 (n-3 fatty acid in the fillets increased, improving the n-6/n-3 ratio. In addition, the incorporation of conjugated linoleic acid in the fish fillets proved well established. This study showed that the use of diets enriched with conjugated linoleic acid and α-linolenic acid results in the incorporation of these acids in the of pacu fish fillets, improving their nutritional quality.

  19. The Polyunsaturated Fatty Acids Arachidonic Acid and Docosahexaenoic Acid Induce Mouse Dendritic Cells Maturation but Reduce T-Cell Responses In Vitro

    Science.gov (United States)

    Carlsson, Johan A.; Wold, Agnes E.; Sandberg, Ann-Sofie; Östman, Sofia M.

    2015-01-01

    Long-chain polyunsaturated fatty acids (PUFAs) might regulate T-cell activation and lineage commitment. Here, we measured the effects of omega-3 (n-3), n-6 and n-9 fatty acids on the interaction between dendritic cells (DCs) and naïve T cells. Spleen DCs from BALB/c mice were cultured in vitro with ovalbumin (OVA) with 50 μM fatty acids; α-linolenic acid, arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid or oleic acid and thereafter OVA-specific DO11.10 T cells were added to the cultures. Fatty acids were taken up by the DCs, as shown by gas chromatography analysis. After culture with arachidonic acid or DHA CD11c+ CD11b+ and CD11c+ CD11bneg DCs expressed more CD40, CD80, CD83, CD86 and PDL-1, while IAd remained unchanged. However, fewer T cells co-cultured with these DCs proliferated (CellTrace Violetlow) and expressed CD69 or CD25, while more were necrotic (7AAD+). We noted an increased proportion of T cells with a regulatory T cell (Treg) phenotype, i.e., when gating on CD4+ FoxP3+ CTLA-4+, CD4+ FoxP3+ Helios+ or CD4+ FoxP3+ PD-1+, in co-cultures with arachidonic acid- or DHA-primed DCs relative to control cultures. The proportion of putative Tregs was inversely correlated to T-cell proliferation, indicating a suppressive function of these cells. With arachidonic acid DCs produced higher levels of prostaglandin E2 while T cells produced lower amounts of IL-10 and IFNγ. In conclusion arachidonic acid and DHA induced up-regulation of activation markers on DCs. However arachidonic acid- and DHA-primed DCs reduced T-cell proliferation and increased the proportion of T cells expressing FoxP3, indicating that these fatty acids can promote induction of regulatory T cells. PMID:26619195

  20. Prenatal long-chain polyunsaturated fatty acid status : the importance of a balanced intake of docosahexaenoic acid and arachidonic acid

    NARCIS (Netherlands)

    Hadders-Algra, Mijna

    2008-01-01

    This review addresses the effect of prenatal long-chain polyunsaturated fatty acid (LCPUFA) status on neuro-developmental outcome. It focuses on the major LPCUFA doxosahexaenoic acid (DNA; 22:6 omega 3) and arachidonic acid (AA; 20:4 omega 6). Due to enzymatic competition high DHA intake results in

  1. Different ratios of docosahexaenoic and eicosapentaenoic acids do not alter growth, nucleic acid and fatty acids of juvenile cobia (Rachycentron canadum).

    Science.gov (United States)

    Xu, Youqing; Ding, Zhaokun; Zhang, Haizhu; Liu, Liang; Wang, Shuqi; Gorge, John

    2009-12-01

    An experiment was performed to study the effect of different ratios of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on the growth, nucleic acid and fatty acids of cobia (Rachycentron canadum) juveniles. The juveniles were fed for 8 weeks using seven treatment diets (D-1-D-7) with the same amount of DHA and EPA (1.50 +/- 0.1% of dried diet), but varying ratios of DHA to EPA (0.90, 1.10, 1.30, 1.50, 1.70, 1.90, 2.10, respectively) and a control diet (D-0, DHA + EPA = 0.8% of dried diet, DHA/EPA = 1.30). At the end of the experiment, the mean body weight (BW) of juveniles fed D-0-D-7 increased significantly (from 6.86 +/- 1.64 in the week 0 to 58.52 +/- 16.45 g at the end of week 8, P cobia juveniles fed D-0-D-7 were significantly higher at the end of 8-week experiment than initially (P cobia juveniles increased with their growth and appeared an obvious positive relationship, especially in the muscle, based on regression analysis. The mean lipid content increased significantly in the liver (from 29.82 +/- 0.99 to 37.47 +/- 3.25% totally) and muscle (from 6.74 +/- 0.25 to 10.63 +/- 0.23% totally) of cobia juveniles (P 0.05). In the muscle and liver of juveniles, EPA decreased with its reduction in the diet; DHA, DHA/EPA ratio and poly unsaturated fatty acids (PUFAs) generally increased with their increment in the diet. The conclusion was drawn that the growth, nucleic acid and fatty acids of cobia juveniles were not significantly affected by different DHA/EPA ratios in our experiments.

  2. The Role of Docosahexaenoic Acid (DHA) in the Control of Obesity and Metabolic Derangements in Breast Cancer.

    Science.gov (United States)

    Molfino, Alessio; Amabile, Maria Ida; Monti, Massimo; Arcieri, Stefano; Rossi Fanelli, Filippo; Muscaritoli, Maurizio

    2016-04-05

    Obesity represents a major under-recognized preventable risk factor for cancer development and recurrence, including breast cancer (BC). Healthy diet and correct lifestyle play crucial role for the treatment of obesity and for the prevention of BC. Obesity is significantly prevalent in western countries and it contributes to almost 50% of BC in older women. Mechanisms underlying obesity, such as inflammation and insulin resistance, are also involved in BC development. Fatty acids are among the most extensively studied dietary factors, whose changes appear to be closely related with BC risk. Alterations of specific ω-3 polyunsaturated fatty acids (PUFAs), particularly low basal docosahexaenoic acid (DHA) levels, appear to be important in increasing cancer risk and its relapse, influencing its progression and prognosis and affecting the response to treatments. On the other hand, DHA supplementation increases the response to anticancer therapies and reduces the undesired side effects of anticancer therapies. Experimental and clinical evidence shows that higher fish consumption or intake of DHA reduces BC cell growth and its relapse risk. Controversy exists on the potential anticancer effects of marine ω-3 PUFAs and especially DHA, and larger clinical trials appear mandatory to clarify these aspects. The present review article is aimed at exploring the capacity of DHA in controlling obesity-related inflammation and in reducing insulin resistance in BC development, progression, and response to therapies.

  3. Formulation of dark chocolate as a carrier to deliver eicosapentaenoic and docosahexaenoic acids: Effects on product quality.

    Science.gov (United States)

    Toker, Omer Said; Konar, Nevzat; Palabiyik, Ibrahim; Rasouli Pirouzian, Haniyeh; Oba, Sirin; Polat, Derya Genc; Poyrazoglu, Ender Sinan; Sagdic, Osman

    2018-07-15

    In this study, dark chocolate enriched with EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) was developed using various forms and origins. Quality characteristics such as physical, thermo-gravimetric, rheological, textural and sensory properties of chocolates were investigated. The highest EPA/DHA stability was determined in samples prepared by free-flowing powder and microencapsulated forms of omega-3 fatty acids (FA). The L ∗ and C ∗ values varied from 32.16-33.37 and 7.45-8.09, respectively for the all samples. Hardness values ranged between 6422 and 8367 N and the use of EPA/DHA in the triglyceride form caused softer chocolate whereas control sample was the hardest sample. Melting and rheological properties were not significantly affected by the studied EPA/DHA sources (P chocolate was the most preferred source whereas sample with algae oil showed the lowest acceptability. According to the results, dark chocolate can be used for delivering omega-3 FA by considering their origin and physical form. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Eicosapentaenoic and docosahexaenoic acids, cognition, and behavior in children with attention-deficit/hyperactivity disorder: a randomized controlled trial.

    Science.gov (United States)

    Milte, Catherine M; Parletta, Natalie; Buckley, Jonathan D; Coates, Alison M; Young, Ross M; Howe, Peter R C

    2012-06-01

    To determine the effects of an eicosapentaenoic acid (EPA)-rich oil and a docosahexaenoic acid (DHA)-rich oil versus an ω-6 polyunsaturated fatty acid-rich safflower oil (control) on literacy and behavior in children with attention-deficit/hyperactivity disorder (ADHD) in a randomized controlled trial. Supplements rich in EPA, DHA, or safflower oil were randomly allocated for 4 mo to 90 Australian children 7 to 12 y old with ADHD symptoms higher than the 90th percentile on the Conners Rating Scales. The effect of supplementation on cognition, literacy, and parent-rated behavior was assessed by linear mixed modeling. Pearson correlations determined associations between the changes in outcome measurements and the erythrocyte fatty acid content (percentage of total) from baseline to 4 mo. There were no significant differences between the supplement groups in the primary outcomes after 4 mo. However, the erythrocyte fatty acid profiles indicated that an increased proportion of DHA was associated with improved word reading (r = 0.394) and lower parent ratings of oppositional behavior (r = 0.392). These effects were more evident in a subgroup of 17 children with learning difficulties: an increased erythrocyte DHA was associated with improved word reading (r = 0.683), improved spelling (r = 0.556), an improved ability to divide attention (r = 0.676), and lower parent ratings of oppositional behavior (r = 0.777), hyperactivity (r = 0.702), restlessness (r = 0.705), and overall ADHD symptoms (r = 0.665). Increases in erythrocyte ω-3 polyunsaturated fatty acids, specifically DHA, may improve literacy and behavior in children with ADHD. The greatest benefit may be observed in children who have comorbid learning difficulties. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Combined application of eicosapentaenoic acid and docosahexaenoic acid on depression in women: a meta-analysis of double-blind randomized controlled trials

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    Yang JR

    2015-08-01

    Full Text Available Jia-run Yang, Dong Han, Zheng-xue Qiao, Xue Tian, Dong Qi, Xiao-hui QiuDepartment of Medical Psychology, Public Health Institute of Harbin Medical University, Harbin, Heilongjiang Province, People’s Republic of ChinaObjectives: Previous randomized controlled trials (RCTs suggest that depression can be effectively treated by omega-3 polyunsaturated fatty acids (PUFAs. Therefore, we conducted this meta-analysis to systematically evaluate the clinical applicability of the combination of docosahexaenoic acid (DHA and eicosapentaenoic acid (EPA, which are the two major bioactive types of PUFAs, in depressed women.Methods: RCTs that compared the combination of DHA and EPA to placebo for short-course treatment of depression in women were systematically reviewed up to March 2015. Outcome measurement was the standardized difference in means in clinical measure of depression severity. Random effect model was performed. Meta-regression analysis was performed to assess the effects of baseline depression scores.Results: Data were obtained from eight RCTs. In these RCTs, 182 patients received placebo and 185 patients received DHA and EPA. The pooled standardized difference in mean was 0.65 with 95% CI = [0.18, 1.12]. There was no relation between the efficacy and the baseline depression scores. The sensitivity analysis found that the combination of EPA and DHA as monotherapy yielded a standardized difference in means of 0.65 (95% CI =0.41, 0.90 without heterogeneity.Discussion: These results indicate a beneficial effect of the combination of EPA and DHA on depressed mood in women compared with placebo. The clinical applicability of EPA and DHA showed greater promise and should be further explored.Keywords: depression, omega-3 polyunsaturated fatty acids, PUFAs, docosahexaenoic acid, DHA, eicosapentaenoic acid, EPA

  6. Natural Docosahexaenoic Acid in the Triglyceride Form Attenuates In Vitro Microglial Activation and Ameliorates Autoimmune Encephalomyelitis in Mice

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    Pilar Mancera

    2017-06-01

    Full Text Available Many neurodegenerative diseases are associated, at least in part, to an inflammatory process in which microglia plays a major role. The effect of the triglyceride form of the omega-3 polyunsaturated fatty acid docosahexaenoic acid (TG-DHA was assayed in vitro and in vivo to assess the protective and anti-inflammatory activity of this compound. In the in vitro study, BV-2 microglia cells were previously treated with TG-DHA and then activated with Lipopolysaccharide (LPS and Interferon-gamma (IFN-γ. TG-DHA treatment protected BV-2 microglia cells from oxidative stress toxicity attenuating NO production and suppressing the induction of inflammatory cytokines. When compared with DHA in the ethyl-ester form, a significant difference in the ability to inhibit NO production in favor of TG-DHA was observed. TG-DHA inhibited significantly splenocyte proliferation but isolated CD4+ lymphocyte proliferation was unaffected. In a mice model of autoimmune encephalomyelitis (EAE, 250 mg/kg/day oral TG-DHA treatment was associated with a significant amelioration of the course and severity of the disease as compared to untreated animals. TG-DHA-treated EAE mice showed a better weight profile, which is a symptom related to a better course of encephalomyelitis. TG-DHA may be a promising therapeutic agent in neuroinflammatory processes and merit to be more extensively studied in human neurodegenerative disorders.

  7. Docosahexaenoic acid inhibits the growth of hormone-dependent prostate cancer cells by promoting the degradation of the androgen receptor.

    Science.gov (United States)

    Hu, Zhimei; Qi, Haixia; Zhang, Ruixue; Zhang, Kun; Shi, Zhemin; Chang, Yanan; Chen, Linfeng; Esmaeili, Mohsen; Baniahmad, Aria; Hong, Wei

    2015-09-01

    Epidemiological and preclinical data have demonstrated the preventative effects of ω-3 polyunsaturated fatty acids, including docosahexaenoic acid (DHA), on prostate cancer. However, there are inconsistencies in these previous studies and the underlying mechanisms remain to be elucidated. In the present study, the androgen receptor (AR), which is a transcription factor involved in cell proliferation and prostate carcinogenesis, was identified as a target of DHA. It was revealed that DHA inhibited hormone‑dependent growth of LNCaP prostate cancer cells. Reverse transcription-quantitative polymerase chain reaction analysis revealed that treatment with DHA caused no alteration in the transcribed mRNA expression levels of the AR gene. However, immunoblotting revealed that this treatment reduces the protein expression level of the AR. The androgen‑induced genes were subsequently repressed by treatment with DHA. It was demonstrated that DHA exhibits no effect on the translation process of the AR, however, it promotes the proteasome‑mediated degradation of the AR. Therefore, the present study provided a novel mechanism by which DHA exhibits an inhibitory effect on growth of prostate cancer cells.

  8. Enhanced Amelioration of High-Fat Diet-Induced Fatty Liver by Docosahexaenoic Acid and Lysine Supplementations

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    Hsin-Yu Lin

    2014-01-01

    Full Text Available Fatty liver disease is the most common pathological condition in the liver. Here, we generated high-fat diet-(HFD- induced nonalcoholic fatty liver disease (NAFLD in mice and tested the effects of docosahexaenoic acid (DHA and lysine during a four-week regular chow (RCfeeding. Our results showed that 1% lysine and the combination of 1% lysine + 1% DHA reduced body weight. Moreover, serum triglyceride levels were reduced by 1% DHA and 1% lysine, whereas serum alanine transaminase activity was reduced by 1% DHA and 1% DHA + 0.5% lysine. Switching to RC reduced hepatic lipid droplet accumulation, which was further reduced by the addition of DHA or lysine. Furthermore, the mRNA expressions of hepatic proinflammatory cytokines were suppressed by DHA and combinations of DHA + lysine, whereas the mRNA for the lipogenic gene, acetyl-CoA carboxylase 1 (ACC1, was suppressed by DHA. In the gonadal adipose tissues, combinations of DHA and lysine inhibited mRNA expression of lipid metabolism-associated genes, including ACC1, fatty acid synthase, lipoprotein lipase, and perilipin. In conclusion, the present study demonstrated that, in conjunction with RC-induced benefits, supplementation with DHA or lysine further ameliorated the high-fat diet-induced NAFLD and provided an alternative strategy to treat, and potentially prevent, NAFLD.

  9. Radioimmunoassay for the determination of free and conjugated abscisic acid

    International Nuclear Information System (INIS)

    Weiler, E.W.

    1979-01-01

    The characterization and application of a radioimmunoassay specific for free and conjugated abscisic acid (ABA) is reported, The antibodies produced against a bovine serum albumin-(+-)-ABA conjugate have a high affinity for ABA (Ka= 1.3 x 10 9 l mol -1 ). Trans, trans-ABA and related compounds, such as xanthoxin, phaseic acid, dihydrophaseic acid, vomifoliol or violaxanthin do not interfere with the assay. The detection limit of this method is 0.25 x 10 -12 mol ABA, the measuring range extends to 20 x 10 -12 mol, and average recoveries are 103%. Because of the high specificity of this immunoassay, no extract purification steps are required prior to analysis. Several hundred plants can be analyzed per day in a semi-automatic assay performance. ABA has been detected in all higher plant families examined, but was absent in the blue-green alga, Spirulina platensis, the liverwort Marchantia polymorpha, and two species of fungi. (orig.) [de

  10. Dietary Docosahexaenoic Acid Improves Cognitive Function, Tissue Sparing, and Magnetic Resonance Imaging Indices of Edema and White Matter Injury in the Immature Rat after Traumatic Brain Injury

    OpenAIRE

    Schober, Michelle E.; Requena, Daniela F.; Abdullah, Osama M.; Casper, T. Charles; Beachy, Joanna; Malleske, Daniel; Pauly, James R.

    2016-01-01

    Traumatic brain injury (TBI) is the leading cause of acquired neurologic disability in children. Specific therapies to treat acute TBI are lacking. Cognitive impairment from TBI may be blunted by decreasing inflammation and oxidative damage after injury. Docosahexaenoic acid (DHA) decreases cognitive impairment, oxidative stress, and white matter injury in adult rats after TBI. Effects of DHA on cognitive outcome, oxidative stress, and white matter injury in the developing rat after experimen...

  11. Determination of conjugated linoleic acid (CLA) concentrations in milk chocolate.

    Science.gov (United States)

    Hurst, W J; Tarka, S M; Dobson, G; Reid, C M

    2001-03-01

    The fatty acids from a series of milk-chocolate-based confectionery samples were analyzed as methyl esters by GC to determine the presence and amount of conjugated linoleic acid (CLA). A single peak corresponding to the 9-cis,11-trans isomer and ranging from less than 0.1% to nearly 0.2% of the total fatty acids, corresponding to up to 0.3 mg per g of chocolate, was observed. One of the chocolate extracts and a milk extract were subjected to silver ion HPLC and GC-MS in order to confirm the identity of the major isomer and tentatively identity minor isomers.

  12. Effects of altered maternal folic acid, vitamin B12 and docosahexaenoic acid on placental global DNA methylation patterns in Wistar rats.

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    Asmita Kulkarni

    Full Text Available Potential adverse effects of excess maternal folic acid supplementation on a vegetarian population deficient in vitamin B(12 are poorly understood. We have previously shown in a rat model that maternal folic acid supplementation at marginal protein levels reduces brain omega-3 fatty acid levels in the adult offspring. We have also reported that reduced docosahexaenoic acid (DHA levels may result in diversion of methyl groups towards DNA in the one carbon metabolic pathway ultimately resulting in DNA methylation. This study was designed to examine the effect of normal and excess folic acid in the absence and presence of vitamin B(12 deficiency on global methylation patterns in the placenta. Further, the effect of maternal omega 3 fatty acid supplementation on the above vitamin B(12 deficient diets was also examined. Our results suggest maternal folic acid supplementation in the absence of vitamin B(12 lowers plasma and placental DHA levels (p<0.05 and reduces global DNA methylation levels (p<0.05. When this group was supplemented with omega 3 fatty acids there was an increase in placental DHA levels and subsequently DNA methylation levels revert back to the levels of the control group. Our results suggest for the first time that DHA plays an important role in one carbon metabolism thereby influencing global DNA methylation in the placenta.

  13. Selective fluorescent detection of aspartic acid and glutamic acid employing dansyl hydrazine dextran conjugate.

    Science.gov (United States)

    Nasomphan, Weerachai; Tangboriboonrat, Pramuan; Tanapongpipat, Sutipa; Smanmoo, Srung

    2014-01-01

    Highly water soluble polymer (DD) was prepared and evaluated for its fluorescence response towards various amino acids. The polymer consists of dansyl hydrazine unit conjugated into dextran template. The conjugation enhances higher water solubility of dansyl hydrazine moiety. Of screened amino acids, DD exhibited selective fluorescence quenching in the presence of aspartic acid (Asp) and glutamic acid (Glu). A plot of fluorescence intensity change of DD against the concentration of corresponding amino acids gave a good linear relationship in the range of 1 × 10(-4) M to 25 × 10(-3) M. This establishes DD as a potential polymeric sensor for selective sensing of Asp and Glu.

  14. Effects of Docosahexaenoic Acid Supplementation on Blood Pressure, Heart Rate, and Serum Lipids in Scottish Men with Hypertension and Hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Miki Sagara

    2011-01-01

    Full Text Available To investigate the effects of daily supplementation with docosahexaenoic acid (DHA on coronary heart disease risks in 38 middle-aged men with hypertension and/or hypercholesterolemia in Scotland, a five-week double-blind placebo-controlled dietary supplementation with either 2 g of DHA or active placebo (1 g of olive oil was conducted. Percent composition of DHA in plasma phospholipids increased significantly in DHA group. Systolic and diastolic blood pressure and heart rate decreased significantly in DHA group, but not in placebo group. High-density lipoprotein cholesterol (HDL-C increased significantly, and total cholesterol (TC/HDL-C and non-HDL-C/HDL-C ratios decreased significantly in both groups. There was no change in TC and non-HDL-C. We conclude that 2 g/day of DHA supplementation reduced coronary heart disease risk factor level improving blood pressure, heart rate, and lipid profiles in hypertensive, hypercholesterolemic Scottish men who do not eat fish on a regular basis.

  15. The significance of fructose and MSG in affecting lipid and docosahexaenoic acid (DHA) production of Aurantiochytrium sp. SW1

    Science.gov (United States)

    Rahman, Shariffah Nurhidayah Syed Abdul; Kalil, Mohd Sahaid; Hamid, Aidil Abdul

    2018-04-01

    Optimization of fermentation medium for the production of docosahexaenoic acid (DHA) by Aurantiochytrium sp. SW1 was carried out. In this study, levels of fructose, monosodium glutamate (MSG) and sea salt were optimized for enhanced lipid and DHA production using response surface methodology (RSM). The design contains a total of 20 runs with 6 central points replication. Cultivation was carried out in 500 mL flasks containing 100 mL nitrogen limited medium at 30°C for 96h. Sequential model sum of squares (SS) revealed that the system was adequately represented by a quadratic model (p<0.0001). ANOVA results showed that fructose and MSG as a single factor has significant positive effect on the DHA content of SW1. The estimated optimal levels of the factors were 100 g/L fructose, 8 g/L MSG and 47% sea salt. Subsequent cultivation employing the suggested values confirmed that the predicted response values were experimentally achievable and reproducible, where 8.82 g/L DHA (51.34% g/g lipid) was achieved.

  16. Coordination of gene expression of arachidonic and docosahexaenoic acid cascade enzymes during human brain development and aging.

    Science.gov (United States)

    Ryan, Veronica H; Primiani, Christopher T; Rao, Jagadeesh S; Ahn, Kwangmi; Rapoport, Stanley I; Blanchard, Helene

    2014-01-01

    The polyunsaturated arachidonic and docosahexaenoic acids (AA and DHA) participate in cell membrane synthesis during neurodevelopment, neuroplasticity, and neurotransmission throughout life. Each is metabolized via coupled enzymatic reactions within separate but interacting metabolic cascades. AA and DHA pathway genes are coordinately expressed and underlie cascade interactions during human brain development and aging. The BrainCloud database for human non-pathological prefrontal cortex gene expression was used to quantify postnatal age changes in mRNA expression of 34 genes involved in AA and DHA metabolism. Expression patterns were split into Development (0 to 20 years) and Aging (21 to 78 years) intervals. Expression of genes for cytosolic phospholipases A2 (cPLA2), cyclooxygenases (COX)-1 and -2, and other AA cascade enzymes, correlated closely with age during Development, less so during Aging. Expression of DHA cascade enzymes was less inter-correlated in each period, but often changed in the opposite direction to expression of AA cascade genes. Except for the PLA2G4A (cPLA2 IVA) and PTGS2 (COX-2) genes at 1q25, highly inter-correlated genes were at distant chromosomal loci. Coordinated age-related gene expression during the brain Development and Aging intervals likely underlies coupled changes in enzymes of the AA and DHA cascades and largely occur through distant transcriptional regulation. Healthy brain aging does not show upregulation of PLA2G4 or PTGS2 expression, which was found in Alzheimer's disease.

  17. Supra-Additive Interaction of Docosahexaenoic Acid and Naproxen and Gastric Safety on the Formalin Test in Rats.

    Science.gov (United States)

    Arroyo-Lira, Arlette Guadalupe; Rodríguez-Ramos, Fernando; Ortiz, Mario I; Castañeda-Hernández, Gilberto; Chávez-Piña, Aracely Evangelina

    2017-11-01

    Preclinical Research The aim of this work was to evaluate the effect of docosahexaenoic acid (DHA) on the pharmacokinetics and pharmacodynamics-nociception-of naproxen in rats, as well as to determine the gastric safety resulting from this combination versus naproxen alone. Female Wistar rats were orally administered DHA, naproxen or the DHA-naproxen mixture at fixed-ratio combination of 1:3. The antinociceptive effect was evaluated using the formalin test. The gastric injury was determined 3 h after naproxen administration. An isobolographic analysis was performed to characterize the antinociceptive interaction between DHA and naproxen. To determine the possibility of pharmacokinetic interactions, the oral bioavailability of naproxen was evaluated in presence and absence of oral DHA. The experimental effective dose ED 30 values (Zexp) were decreased from theoretical additive dose values (Zadd; P supra-additive interaction. The oral administration of DHA increased the pharmacokinetic parameter AUC 0- t of naproxen (P supra-additive antinociceptive effect in the formalin test so that this combination could be useful to management of inflammatory pain. Drug Dev Res 78 : 332-339, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  18. Coordination of gene expression of arachidonic and docosahexaenoic acid cascade enzymes during human brain development and aging.

    Directory of Open Access Journals (Sweden)

    Veronica H Ryan

    Full Text Available The polyunsaturated arachidonic and docosahexaenoic acids (AA and DHA participate in cell membrane synthesis during neurodevelopment, neuroplasticity, and neurotransmission throughout life. Each is metabolized via coupled enzymatic reactions within separate but interacting metabolic cascades.AA and DHA pathway genes are coordinately expressed and underlie cascade interactions during human brain development and aging.The BrainCloud database for human non-pathological prefrontal cortex gene expression was used to quantify postnatal age changes in mRNA expression of 34 genes involved in AA and DHA metabolism.Expression patterns were split into Development (0 to 20 years and Aging (21 to 78 years intervals. Expression of genes for cytosolic phospholipases A2 (cPLA2, cyclooxygenases (COX-1 and -2, and other AA cascade enzymes, correlated closely with age during Development, less so during Aging. Expression of DHA cascade enzymes was less inter-correlated in each period, but often changed in the opposite direction to expression of AA cascade genes. Except for the PLA2G4A (cPLA2 IVA and PTGS2 (COX-2 genes at 1q25, highly inter-correlated genes were at distant chromosomal loci.Coordinated age-related gene expression during the brain Development and Aging intervals likely underlies coupled changes in enzymes of the AA and DHA cascades and largely occur through distant transcriptional regulation. Healthy brain aging does not show upregulation of PLA2G4 or PTGS2 expression, which was found in Alzheimer's disease.

  19. Safety of docosahexaenoic acid (DHA) administered as DHA ethyl ester in a 9-month toxicity study in dogs.

    Science.gov (United States)

    Dahms, Irina; Beilstein, Paul; Bonnette, Kimberly; Salem, Norman

    2016-06-01

    DHA Ethyl Ester (DHA-EE) is a 90% concentrated ethyl ester of docosahexaenoic acid manufactured from the microalgal oil. The objective of the 9-month study was to evaluate safety of DHA-EE administered to beagle dogs at dose levels 150, 1000 and 2000 mg/kg bw/day by oral gavage and to determine reversibility of any findings after a 2-month recovery period. DHA-EE was well tolerated at all doses. There were observations of dry flaky skin with occasional reddened areas at doses ≥1000 mg/kg bw/day. These findings lacked any microscopic correlate and were no longer present after the recovery period. There were no toxicologically relevant findings in body weights, body weight gains, food consumption, ophthalmological examinations, and ECG measurements. Test article-related changes in hematology parameters were limited to decreases in reticulocyte count in the high-dose males and considered non-adverse. In clinical chemistry parameters, dose-related decreases in cholesterol and triglycerides levels were observed at all doses in males and females and attributed to the known lipid-lowering effects of DHA. There were no effects on other clinical chemistry, urinalysis or coagulation parameters. There were no abnormal histopathology findings attributed to test article. The No-Observable-Adverse-Effect Level of DHA-EE was established at 2000 mg/kg bw/day for both genders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Feeding a Diet Enriched in Docosahexaenoic Acid to Lactating Dams Improves the Tolerance Response to Egg Protein in Suckled Pups

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    Caroline Richard

    2016-02-01

    Full Text Available The objective of this study was to determine the effect of feeding a maternal diet supplemented with docosahexaenoic acid (DHA during the suckling period on the development of the immune system and oral tolerance (OT in offspring. Dams were randomized to consume one of two nutritionally adequate diets throughout the suckling period: control (N = 12, 0% DHA or DHA (N = 8, 0.9% DHA diet. At 11 days, pups from each dam were randomly assigned to a mucosal OT challenge: the placebo or the ovalbumin (OVA treatment. At three weeks, plasma immunoglobulins and splenocyte cytokine production ex vivo were measured. OVA-tolerized pups had a lower Th2 (IL-13 response to OVA despite the presence of more activated T cells and memory cells (CD27+, all p < 0.05. Feeding a high DHA diet improved the ability of splenocytes to respond to mitogens toward a skewed Th1 response and led to a higher IL-10 and a lower TGF-β production after stimulation with OVA (all p < 0.05. Untolerized DHA-fed pups had lower plasma concentrations of OVA-specific immunoglobulin E (p for interaction < 0.05. Overall, feeding a high DHA maternal diet improves the tolerance response in untolerized suckled pups in a direction that is thought to be beneficial for the establishment of OT.

  1. Plasma incorporation, apparent retroconversion and β-oxidation of 13C-docosahexaenoic acid in the elderly

    Directory of Open Access Journals (Sweden)

    Brenna J Thomas

    2011-01-01

    Full Text Available Abstract Background Higher fish or higher docosahexaenoic acid (DHA intake normally correlates positively with higher plasma DHA level, but recent evidence suggests that the positive relationship between intake and plasma levels of DHA is less clear in the elderly. Methods We compared the metabolism of 13C-DHA in six healthy elderly (mean - 77 y old and six young adults (mean - 27 y old. All participants were given a single oral dose of 50 mg of uniformly labelled 13C-DHA. Tracer incorporation into fatty acids of plasma triglycerides, free fatty acids, cholesteryl esters and phospholipids, as well as apparent retroconversion and β-oxidation of 13C-DHA were evaluated 4 h, 24 h, 7d and 28d later. Results Plasma incorporation and β-oxidation of 13C-DHA reached a maximum within 4 h in both groups, but 13C-DHA was transiently higher in all plasma lipids of the elderly 4 h to 28d later. At 4 h post-dose, 13C-DHA β-oxidation was 1.9 times higher in the elderly, but over 7d, cumulative β-oxidation of 13C-DHA was not different in the two groups (35% in the elderly and 38% in the young. Apparent retroconversion of 13C-DHA was well below 10% of 13C-DHA recovered in plasma at all time points, and was 2.1 times higher in the elderly 24 h and 7d after tracer intake. Conclusions We conclude that 13C-DHA metabolism changes significantly during healthy aging. Since DHA is a potentially important molecule in neuro-protection, these changes may be relevant to the higher vulnerability of the elderly to cognitive decline.

  2. The effect of eicosapentaenoic and docosahexaenoic acid on protein synthesis and breakdown in murine C2C12 myotubes

    International Nuclear Information System (INIS)

    Kamolrat, Torkamol; Gray, Stuart R.

    2013-01-01

    Highlights: ► EPA can enhance protein synthesis and retard protein breakdown in muscle cells. ► These effects were concurrent with increases in p70s6k and FOXO3a phosphorylation. ► EPA may be a useful tool in the treatment of muscle wasting conditions. -- Abstract: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been found to stimulate protein synthesis with little information regarding their effects on protein breakdown. Furthermore whether there are distinct effects of EPA and DHA remains to be established. The aim of the current study was to determine the distinct effects of EPA and DHA on protein synthesis, protein breakdown and signalling pathways in C2C12 myotubes. Fully differentiated C2C12 cells were incubated for 24 h with 0.1% ethanol (control), 50 μM EPA or 50 μM DHA prior to experimentation. After serum (4 h) and amino acid (1 h) starvation cells were stimulated with 2 mM L-leucine and protein synthesis measured using 3 H-labelled phenylalanine. Protein breakdown was measured using 3 H-labelled phenylalanine and signalling pathways (Akt, mTOR, p70S6k, 4EBP1, rps6 and FOXO3a) via Western blots. Data revealed that after incubation with EPA protein synthesis was 25% greater (P < 0.05) compared to control cells, with no effect of DHA. Protein breakdown was 22% (P < 0.05) lower, compared to control cells, after incubation with EPA, with no effect of DHA. Analysis of signalling pathways revealed that both EPA and DHA incubation increased (P < 0.05) p70s6k phosphorylation, EPA increased (P < 0.05) FOXO3a phosphorylation, with no alteration in other signalling proteins. The current study has demonstrated distinct effects of EPA and DHA on protein metabolism with EPA showing a greater ability to result in skeletal muscle protein accretion

  3. Maternal liver docosahexaenoic acid (DHA) stores are increased via higher serum unesterified DHA uptake in pregnant long Evans rats.

    Science.gov (United States)

    Metherel, Adam H; Kitson, Alex P; Domenichiello, Anthony F; Lacombe, R J Scott; Hopperton, Kathryn E; Trépanier, Marc-Olivier; Alashmali, Shoug M; Lin, Lin; Bazinet, Richard P

    2017-08-01

    Maternal docosahexaenoic acid (DHA, 22:6n-3) supplies the developing fetus during pregnancy; however, the mechanisms are unclear. We utilized pregnant rats to determine rates of DHA accretion, tissue unesterified DHA uptake and whole-body DHA synthesis-secretion. Female rats maintained on a DHA-free, 2% α-linolenic acid diet were either:1) sacrificed at 56 days for baseline measures, 2) mated and sacrificed at 14-18 days of pregnancy or 3) or sacrificed at 14-18 days as age-matched virgin controls. Maternal brain, adipose, liver and whole body fatty acid concentrations was determined for balance analysis, and kinetic modeling was used to determine brain and liver plasma unesterified DHA uptake and whole-body DHA synthesis-secretion rates. Total liver DHA was significantly higher in pregnant (95±5 μmol) versus non-pregnant (49±5) rats with no differences in whole-body DHA synthesis-secretion rates. However, liver uptake of plasma unesterified DHA was 3.8-fold higher in pregnant animals compared to non-pregnant controls, and periuterine adipose DHA was lower in pregnant (0.89±0.09 μmol/g) versus non-pregnant (1.26±0.06) rats. In conclusion, higher liver DHA accretion during pregnancy appears to be driven by higher unesterified DHA uptake, potentially via DHA mobilization from periuterine adipose for delivery to the fetus during the brain growth spurt. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. The effect of eicosapentaenoic and docosahexaenoic acid on protein synthesis and breakdown in murine C2C12 myotubes

    Energy Technology Data Exchange (ETDEWEB)

    Kamolrat, Torkamol [Musculoskeletal Research Programme, Institute of Medical Sciences, University of Aberdeen, AB25 2ZD (United Kingdom); Gray, Stuart R., E-mail: s.r.gray@abdn.ac.uk [Musculoskeletal Research Programme, Institute of Medical Sciences, University of Aberdeen, AB25 2ZD (United Kingdom)

    2013-03-22

    Highlights: ► EPA can enhance protein synthesis and retard protein breakdown in muscle cells. ► These effects were concurrent with increases in p70s6k and FOXO3a phosphorylation. ► EPA may be a useful tool in the treatment of muscle wasting conditions. -- Abstract: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been found to stimulate protein synthesis with little information regarding their effects on protein breakdown. Furthermore whether there are distinct effects of EPA and DHA remains to be established. The aim of the current study was to determine the distinct effects of EPA and DHA on protein synthesis, protein breakdown and signalling pathways in C2C12 myotubes. Fully differentiated C2C12 cells were incubated for 24 h with 0.1% ethanol (control), 50 μM EPA or 50 μM DHA prior to experimentation. After serum (4 h) and amino acid (1 h) starvation cells were stimulated with 2 mM L-leucine and protein synthesis measured using {sup 3}H-labelled phenylalanine. Protein breakdown was measured using {sup 3}H-labelled phenylalanine and signalling pathways (Akt, mTOR, p70S6k, 4EBP1, rps6 and FOXO3a) via Western blots. Data revealed that after incubation with EPA protein synthesis was 25% greater (P < 0.05) compared to control cells, with no effect of DHA. Protein breakdown was 22% (P < 0.05) lower, compared to control cells, after incubation with EPA, with no effect of DHA. Analysis of signalling pathways revealed that both EPA and DHA incubation increased (P < 0.05) p70s6k phosphorylation, EPA increased (P < 0.05) FOXO3a phosphorylation, with no alteration in other signalling proteins. The current study has demonstrated distinct effects of EPA and DHA on protein metabolism with EPA showing a greater ability to result in skeletal muscle protein accretion.

  5. The induction of apoptosis in pre-malignant keratinocytes by omega-3 polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) is inhibited by albumin.

    Science.gov (United States)

    Nikolakopoulou, Zacharoula; Shaikh, Mushfiq Hassan; Dehlawi, Hebah; Michael-Titus, Adina Teodora; Parkinson, Eric Kenneth

    2013-04-12

    The long chain omega-3 polyunsaturated fatty acids (PUFA) have been reported to exert anti-cancer effects. At this study we tested the effect of the omega-3 PUFA, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), on pre-malignant keratinocytes growth in the well-characterised human pre-malignant epidermal cell line, HaCaT and attempted to identify a PUFA serum antagonist. Both EPA and DHA inhibited HaCaT growth and induced apoptosis. At the 10% (v/v) foetal bovine serum (FBS) medium, limited growth inhibition (3-20% for 50μM DHA and EPA respectively) and negligible apoptosis were observed with PUFA use. However, at 3% (v/v) FBS medium, 30-50μM of PUFA caused impressive levels of growth inhibition (82-83% for 50μM DHA and EPA respectively) and increase of apoptosis (8-19% increase in 72h). None of the numerous serum growth factors present in FBS or the antioxidant n-tert-butyl-α-phenylnitrone could inhibit the PUFA-induced cytotoxicity. In contrast, bovine and human albumin (0.1-0.3%, w/v) significantly antagonized the growth inhibitory and apoptosis-inducing effects of PUFA. In conclusion, we have shown for the first time that omega-3 PUFA inhibit the growth and induce apoptosis of pre-malignant keratinocytes and identified albumin as a major antagonistic factor in serum that could limit their effectiveness at pharmacologically-achievable doses. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  6. A Taiwanese food frequency questionnaire correlates with plasma docosahexaenoic acid but not with plasma eicosapentaenoic acid levels: questionnaires and plasma biomarkers.

    Science.gov (United States)

    Chien, Kuo-Liong; Lee, Meei-Shyuan; Tsai, Yi-Tsen; Chen, Pey-Rong; Lin, Hung-Ju; Hsu, Hsiu-Ching; Lee, Yuan-The; Chen, Ming-Fong

    2013-02-16

    Little evidence is available for the validity of dietary fish and polyunsaturated fatty acid intake derived from interviewer-administered questionnaires and plasma docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) concentration. We estimated the correlation of DHA and EPA intake from both questionnaires and biochemical measurements. Ethnic Chinese adults with a mean (± SD) age of 59.8 (±12.8) years (n = 297) (47% women) who completed a 38-item semi-quantitative food-frequency questionnaire and provided a plasma sample were enrolled. Plasma fatty acids were analyzed by capillary gas chromatography. The Spearmen rank correlation coefficients between the intake of various types of fish and marine n-3 fatty acids as well as plasma DHA were significant, ranging from 0.20 to 0.33 (P food frequency questionnaire, were correlated with the percentages of these fatty acids in plasma, and in particular with plasma DHA. Plasma DHA levels were correlated to dietary intake of long-chain n-3 fatty acids.

  7. Effects of Short-Term Docosahexaenoic Acid Supplementation on Markers of Inflammation after Eccentric Strength Exercise in Women.

    Science.gov (United States)

    Corder, Katherine E; Newsham, Katherine R; McDaniel, Jennifer L; Ezekiel, Uthayashanker R; Weiss, Edward P

    2016-03-01

    The omega-3 fatty acid docosahexaenoic acid (DHA) has anti-inflammatory and anti-nociceptive (pain inhibiting) effects. Because strenuous exercise often results in local inflammation and pain, we hypothesized that DHA supplementation attenuates the rise in markers of local muscle inflammation and delayed onset muscle soreness (DOMS) that occur after eccentric strength exercise. Twenty-seven, healthy women (33 ± 2 y, BMI 23.1±1.0 kg·m(-2)) were randomized to receive 9d of 3000 mg/d DHA or placebo in a double-blind fashion. On day 7 of the supplementation period, the participants performed 4 sets of maximal-effort eccentric biceps curl exercise. Before and 48h after the eccentric exercise, markers of inflammation were measured including measures of muscle soreness (10-point visual analog pain scale, VAS), swelling (arm circumference), muscle stiffness (active and passive elbow extension), skin temperature, and salivary C-reactive protein (CRP) concentrations. As expected, muscle soreness and arm circumference increased while active and passive elbow extension decreased. The increase in soreness was 23% less in the DHA group (48h increase in VAS soreness ratings: 4.380.4 vs. 5.600.5, p=0.02). Furthermore, the number of subjects who were able to achieve full active elbow extension 48h after eccentric exercise was greater in the DHA group (71% vs. 15%, p = 0.006), indicating significantly less muscle stiffness. No between-group differences were observed for passive elbow extension (p = 0.78) or arm swelling (p = 0.75). Skin temperature and salivary CRP concentrations did not change from baseline to 48h after exercise in either group. These findings indicate that short-term DHA supplementation reduces exercise-induced muscle soreness and stiffness. Therefore, in addition to other health benefits that n-3 fatty acids have been associated with, DHA supplementation could be beneficial for improving tolerance to new and/or strenuous exercise programs and thereby might

  8. Docosahexaenoic acid prevents paraquat-induced reactive oxygen species production in dopaminergic neurons via enhancement of glutathione homeostasis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hyoung Jun; Han, Jeongsu; Jang, Yunseon; Kim, Soo Jeong; Park, Ji Hoon; Seo, Kang Sik [Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon (Korea, Republic of); Jeong, Soyeon; Shin, Soyeon; Lim, Kyu [Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon (Korea, Republic of); Infection Signaling Network Research Center, Chungnam National University, Daejeon (Korea, Republic of); Heo, Jun Young, E-mail: junyoung3@gmail.com [Brainscience Institute, Chungnam National University, Daejeon (Korea, Republic of); Kweon, Gi Ryang, E-mail: mitochondria@cnu.ac.kr [Department of Biochemistry, College of Medicine, Chungnam National University, Daejeon (Korea, Republic of); Infection Signaling Network Research Center, Chungnam National University, Daejeon (Korea, Republic of)

    2015-01-30

    Highlights: • DHA prevents PQ-induced dopaminergic neuronal loss via decreasing of excessive ROS. • DHA increases GR and GCLm derivate GSH pool by enhancement of Nrf2 expression. • Protective mechanism is removal of PQ-induced ROS via DHA-dependent GSH pool. • DHA may be a good preventive strategy for Parkinson’s disease (PD) therapy. - Abstract: Omega-3 polyunsaturated fatty acid levels are reduced in the substantia nigra area in Parkinson’s disease patients and animal models, implicating docosahexaenoic acid (DHA) as a potential treatment for preventing Parkinson’s disease and suggesting the need for investigations into how DHA might protect against neurotoxin-induced dopaminergic neuron loss. The herbicide paraquat (PQ) induces dopaminergic neuron loss through the excessive production of reactive oxygen species (ROS). We found that treatment of dopaminergic SN4741 cells with PQ reduced cell viability in a dose-dependent manner, but pretreatment with DHA ameliorated the toxic effect of PQ. To determine the toxic mechanism of PQ, we measured intracellular ROS content in different organelles with specific dyes. As expected, all types of ROS were increased by PQ treatment, but DHA pretreatment selectively decreased cytosolic hydrogen peroxide content. Furthermore, DHA treatment-induced increases in glutathione reductase and glutamate cysteine ligase modifier subunit (GCLm) mRNA expression were positively correlated with glutathione (GSH) content. Consistent with this increase in GCLm mRNA levels, Western blot analysis revealed that DHA pretreatment increased nuclear factor-erythroid 2 related factor 2 (Nrf2) protein levels. These findings indicate that DHA prevents PQ-induced neuronal cell loss by enhancing Nrf2-regulated GSH homeostasis.

  9. Eicosapentaenoic and Docosahexaenoic Acids Attenuate Progression of Albuminuria in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease.

    Science.gov (United States)

    Elajami, Tarec K; Alfaddagh, Abdulhamied; Lakshminarayan, Dharshan; Soliman, Michael; Chandnani, Madhuri; Welty, Francine K

    2017-07-14

    Albuminuria is a marker of inflammation and an independent predictor of cardiovascular morbidity and mortality. The current study evaluated whether eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation attenuates progression of albuminuria in subjects with coronary artery disease. Two-hundred sixty-two subjects with stable coronary artery disease were randomized to either Lovaza (1.86 g of EPA and 1.5 g of DHA daily) or no Lovaza (control) for 1 year. Percent change in urine albumin-to-creatinine ratio (ACR) was compared. Mean (SD) age was 63.3 (7.6) years; 17% were women and 30% had type 2 diabetes mellitus. In nondiabetic subjects, no change in urine ACR occurred in either the Lovaza or control groups. In contrast, ACR increased 72.3% ( P diabetic subjects not receiving Lovaza, whereas those receiving Lovaza had no change. In diabetic subjects on an angiotensin-converting enzyme-inhibitor or angiotensin-receptor blocker, those receiving Lovaza had no change in urine ACR, whereas those not receiving Lovaza had a 64.2% increase ( P type 2 diabetes mellitus and coronary artery disease, most of whom were on an angiotensin-converting enzyme-inhibitor or angiotensin-receptor blocker. Thus, EPA and DHA supplementation should be considered as additional therapy to an angiotensin-converting enzyme-inhibitor or angiotensin-receptor blocker in subjects with type 2 diabetes mellitus and coronary artery disease. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01624727. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  10. Effect of Dietary Docosahexaenoic Acid Supplementation on the Participation of Vasodilator Factors in Aorta from Orchidectomized Rats.

    Directory of Open Access Journals (Sweden)

    Diva M Villalpando

    Full Text Available Benefits of n-3 polyunsaturated fatty acids (PUFAs against cardiovascular diseases have been reported. Vascular tone regulation is largely mediated by endothelial factors whose release is modulated by sex hormones. Since the incidence of cardiovascular pathologies has been correlated with decreased levels of sex hormones, the aim of this study was to analyze whether a diet supplemented with the specific PUFA docosahexaenoic acid (DHA could prevent vascular changes induced by an impaired gonadal function. For this purpose, control and orchidectomized rats were fed with a standard diet supplemented with 5% (w/w sunflower oil or with 3% (w/w sunflower oil plus 2% (w/w DHA. The lipid profile, the blood pressure, the production of prostanoids and nitric oxide (NO, and the redox status of biological samples from control and orchidectomized rats, fed control or DHA-supplemented diet, were analyzed. The vasodilator response and the contribution of NO, prostanoids and hyperpolarizing mechanisms were also studied. The results showed that orchidectomy negatively affected the lipid profile, increased the production of prostanoids and reactive oxygen species (ROS, and decreased NO production and the antioxidant capacity, as well as the participation of hyperpolarizing mechanisms in the vasodilator responses. The DHA-supplemented diet of the orchidectomized rats decreased the release of prostanoids and ROS, while increasing NO production and the antioxidant capacity, and it also improved the lipid profile. Additionally, it restored the participation of hyperpolarizing mechanisms by activating potassium. Since the modifications induced by the DHA-supplemented diet were observed in the orchidectomized, but not in the healthy group, DHA seems to exert cardioprotective effects in physiopathological situations in which vascular dysfunction exists.

  11. A Mini-Review on the Effect of Docosahexaenoic Acid (DHA on Cerulein-Induced and Hypertriglyceridemic Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Yoo Kyung Jeong

    2017-10-01

    Full Text Available Acute pancreatitis refers to the sudden inflammation of the pancreas. It is associated with premature activation and release of digestive enzymes into the pancreatic interstitium and systemic circulation, resulting in pancreatic tissue autodigestion and multiple organ dysfunction, as well as with increased cytokine production, ultimately leading to deleterious local and systemic effects. Although mechanisms involved in pathogenesis of acute pancreatitis have not been completely elucidated, oxidative stress is regarded as a major risk factor. In human acute pancreatitis, lipid peroxide levels in pancreatic tissues increase. Docosahexaenoic acid (DHA, an omega-3 polyunsaturated fatty acid (C22:6n-3, exerts anti-inflammatory and antioxidant effects on various cells. Previous studies have shown that DHA activates peroxisome proliferator-activated receptor-γ and induces catalase, which inhibits oxidative stress-mediated inflammatory signaling required for cytokine expression in experimental acute pancreatitis using cerulein. Cerulein, a cholecystokinin analog, induces intra-acinar activation of trypsinogen in the pancreas, which results in human acute pancreatitis-like symptoms. Therefore, DHA supplementation may be beneficial for preventing or inhibiting acute pancreatitis development. Since DHA reduces serum triglyceride levels, addition of DHA to lipid-lowering drugs like statins has been investigated to reduce hypertriglyceridemic acute pancreatitis. However, high DHA concentrations increase cytosolic Ca2+, which activates protein kinase C and may induce hyperlipidemic acute pancreatitis. In this review, effect of DHA on cerulein-induced and hypertriglyceridemic acute pancreatitis has been discussed. The relation of high concentration of DHA to hyperlipidemic acute pancreatitis has been included.

  12. Docosahexaenoic acid prevents paraquat-induced reactive oxygen species production in dopaminergic neurons via enhancement of glutathione homeostasis

    International Nuclear Information System (INIS)

    Lee, Hyoung Jun; Han, Jeongsu; Jang, Yunseon; Kim, Soo Jeong; Park, Ji Hoon; Seo, Kang Sik; Jeong, Soyeon; Shin, Soyeon; Lim, Kyu; Heo, Jun Young; Kweon, Gi Ryang

    2015-01-01

    Highlights: • DHA prevents PQ-induced dopaminergic neuronal loss via decreasing of excessive ROS. • DHA increases GR and GCLm derivate GSH pool by enhancement of Nrf2 expression. • Protective mechanism is removal of PQ-induced ROS via DHA-dependent GSH pool. • DHA may be a good preventive strategy for Parkinson’s disease (PD) therapy. - Abstract: Omega-3 polyunsaturated fatty acid levels are reduced in the substantia nigra area in Parkinson’s disease patients and animal models, implicating docosahexaenoic acid (DHA) as a potential treatment for preventing Parkinson’s disease and suggesting the need for investigations into how DHA might protect against neurotoxin-induced dopaminergic neuron loss. The herbicide paraquat (PQ) induces dopaminergic neuron loss through the excessive production of reactive oxygen species (ROS). We found that treatment of dopaminergic SN4741 cells with PQ reduced cell viability in a dose-dependent manner, but pretreatment with DHA ameliorated the toxic effect of PQ. To determine the toxic mechanism of PQ, we measured intracellular ROS content in different organelles with specific dyes. As expected, all types of ROS were increased by PQ treatment, but DHA pretreatment selectively decreased cytosolic hydrogen peroxide content. Furthermore, DHA treatment-induced increases in glutathione reductase and glutamate cysteine ligase modifier subunit (GCLm) mRNA expression were positively correlated with glutathione (GSH) content. Consistent with this increase in GCLm mRNA levels, Western blot analysis revealed that DHA pretreatment increased nuclear factor-erythroid 2 related factor 2 (Nrf2) protein levels. These findings indicate that DHA prevents PQ-induced neuronal cell loss by enhancing Nrf2-regulated GSH homeostasis

  13. Intraperitoneal administration of docosahexaenoic acid for 14days increases serum unesterified DHA and seizure latency in the maximal pentylenetetrazol model.

    Science.gov (United States)

    Trépanier, Marc-Olivier; Lim, Joonbum; Lai, Terence K Y; Cho, Hye Jin; Domenichiello, Anthony F; Chen, Chuck T; Taha, Ameer Y; Bazinet, Richard P; Burnham, W M

    2014-04-01

    Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid (n-3 PUFA) which has been shown to raise seizure thresholds following acute administration in rats. The aims of the present experiment were the following: 1) to test whether subchronic DHA administration raises seizure threshold in the maximal pentylenetetrazol (PTZ) model 24h following the last injection and 2) to determine whether the increase in seizure threshold is correlated with an increase in serum and/or brain DHA. Animals received daily intraperitoneal (i.p.) injections of 50mg/kg of DHA, DHA ethyl ester (DHA EE), or volume-matched vehicle (albumin/saline) for 14days. On day 15, one subset of animals was seizure tested in the maximal PTZ model (Experiment 1). In a separate (non-seizure tested) subset of animals, blood was collected, and brains were excised following high-energy, head-focused microwave fixation. Lipid analysis was performed on serum and brain (Experiment 2). For data analysis, the DHA and DHA EE groups were combined since they did not differ significantly from each other. In the maximal PTZ model, DHA significantly increased seizure latency by approximately 3-fold as compared to vehicle-injected animals. This increase in seizure latency was associated with an increase in serum unesterified DHA. Total brain DHA and brain unesterified DHA concentrations, however, did not differ significantly in the treatment and control groups. An increase in serum unesterified DHA concentration reflecting increased flux of DHA to the brain appears to explain changes in seizure threshold, independent of changes in brain DHA concentrations. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Effects of purified eicosapentaenoic and docosahexaenoic acids in nonalcoholic fatty liver disease: results from the Welcome* study.

    Science.gov (United States)

    Scorletti, Eleonora; Bhatia, Lokpal; McCormick, Keith G; Clough, Geraldine F; Nash, Kathryn; Hodson, Leanne; Moyses, Helen E; Calder, Philip C; Byrne, Christopher D

    2014-10-01

    There is no licensed treatment for non-alcoholic fatty liver disease (NAFLD), a condition that increases risk of chronic liver disease, type 2 diabetes and cardiovascular disease. We tested whether 15-18 months treatment with docosahexaenoic acid (DHA) plus eicosapentaenoic acid (EPA) (Omacor/Lovaza) (4 g/day) decreased liver fat and improved two histologically-validated liver fibrosis biomarker scores (primary outcomes). Patients with NAFLD were randomised in a double blind placebo-controlled trial [DHA+EPA(n=51), placebo(n=52)]. We quantified liver fat percentage (%) by magnetic resonance spectroscopy in three liver zones. We measured liver fibrosis using two validated scores. We tested adherence to the intervention (Omacor group) and contamination (with DHA and EPA) (placebo group) by measuring erythrocyte percentage DHA and EPA enrichment (gas chromatography). We undertook multivariable linear regression to test effects of: a) DHA+EPA treatment (ITT analyses) and b) erythrocyte DHA and EPA enrichment (secondary analysis). Median (IQR) baseline and end of study liver fat% were 21.7 (19.3) and 19.7 (18.0) (placebo), and 23.0 (36.2) and 16.3 (22.0), (DHA+EPA). In the fully adjusted regression model there was a trend towards improvement in liver fat% with DHA+EPA treatment (β=-3.64 (95%CI -8.0,0.8); p=0.1) but there was evidence of contamination in the placebo group and variable adherence to the intervention in the Omacor group. Further regression analysis showed that DHA enrichment was independently associated with a decrease in liver fat% (for each 1% enrichment, β=-1.70 (95%CI -2.9,-0.5); p=0.007). No improvement in the fibrosis scores occurred. Conclusion. Erythrocyte DHA enrichment with DHA+EPA treatment is linearly associated with decreased liver fat%. Substantial decreases in liver fat% can be achieved with high percentage erythrocyte DHA enrichment in NAFLD. (Hepatology 2014;).

  15. Analysis of Peptides and Conjugates by Amino Acid Analysis

    DEFF Research Database (Denmark)

    Højrup, Peter

    2015-01-01

    Amino acid analysis is a highly accurate method for characterization of the composition of synthetic peptides. Together with mass spectrometry, it gives a reliable control of peptide quality and quantity before conjugation and immunization.Peptides are hydrolyzed, preferably in gas phase, with 6 M...... HCl at 110 °C for 20-24 h and the resulting amino acids analyzed by ion-exchange chromatography with post-column ninhydrin derivatization. Depending on the hydrolysis conditions, tryptophan is destroyed, and cysteine also, unless derivatized, and the amides, glutamine and asparagine, are deamidated...... to glutamic acid and aspartic acid, respectively. Three different ways of calculating results are suggested, and taking the above limitations into account, a quantitation better than 5 % can usually be obtained....

  16. Sex-specific effects of docosahexaenoic acid (DHA) on the microbiome and behavior of socially-isolated mice.

    Science.gov (United States)

    Davis, Daniel J; Hecht, Patrick M; Jasarevic, Eldin; Beversdorf, David Q; Will, Matthew J; Fritsche, Kevin; Gillespie, Catherine H

    2017-01-01

    Dietary supplementation with the long-chain omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) has been shown to have a beneficial effect on reducing the symptoms associated with several neuropsychiatric conditions including anxiety and depression. However, the mechanisms underlying this effect remain largely unknown. Increasing evidence suggests that the vast repertoire of commensal bacteria within the gut plays a critical role in regulating various biological processes in the brain and may contribute to neuropsychiatric disease risk. The present study determined the contribution of DHA on anxiety and depressive-like behaviors through modulation of the gut microbiota in a paradigm of social isolation. Adult male and female mice were subjected to social isolation for 28days and then placed either on a control diet or a diet supplemented with 0.1% or 1.0% DHA. Fecal pellets were collected both 24h and 7days following the introduction of the new diets. Behavioral testing revealed that male mice fed a DHA diet, regardless of dose, exhibited reduced anxiety and depressive-like behaviors compared to control fed mice while no differences were observed in female mice. As the microbiota-brain-axis has been recently implicated in behavior, composition of microbial communities were analyzed to examine if these sex-specific effects of DHA may be associated with changes in the gut microbiota (GM). Clear sex differences were observed with males and females showing distinct microbial compositions prior to DHA supplementation. The introduction of DHA into the diet also induced sex-specific interactions on the GM with the fatty acid producing a significant effect on the microbial profiles in males but not in females. Interestingly, levels of Allobaculum and Ruminococcus were found to significantly correlate with the behavioral changes observed in the male mice. Predictive metagenome analysis using PICRUSt was performed on the fecal samples collected from males and

  17. Minimal food effect for eicosapentaenoic acid and docosahexaenoic acid bioavailability from omega-3-acid ethyl esters with an Advanced Lipid TechnologiesTM (ALT®)-based formulation.

    Science.gov (United States)

    Lopez-Toledano, Miguel A; Thorsteinsson, Thorsteinn; Daak, Ahmed A; Maki, Kevin C; Johns, Colleen; Rabinowicz, Adrian L; Sancilio, Frederick D

    The absorption of eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) omega-3-acid ethyl esters (EEs) is influenced by food. There is a need for a formulation of EE that is less impacted by food effect. SC401 is a novel Advanced Lipid Technologies-based formulation of EPA-EE and DHA-EE. In the presence of an aqueous medium, Advanced Lipid Technologies forms stable micelles in situ independent of bile salt secretion. This effect is hypothesized to improve EPA-EE and DHA-EE bioavailability while it helps mitigate the food effect associated with their consumption. The aim of the article was to assess the effect of food on the bioavailability of DHA and EPA after a single oral dose of 1530 mg omega-3 fatty acids EE (SC401) in 24 healthy subjects under fasted and low-fat (9% of total calories from fat) and high-fat (50% of total calories from fat) meal conditions. This was a randomized, open-label, single-dose, 3-period, 3-way crossover study. Blood samples for pharmacokinetic analyses were taken at predose and at 0.5, 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 10, 12 and 24 hours postdose. To assess the safety of the intervention, active monitoring of adverse events, physical examinations, vital signs, clinical laboratory assessments (chemistry, hematology, and urinalysis), and 12-lead electrocardiograms were conducted. SC401 showed high bioavailability of both EPA and DHA in fasted, low-fat meal, and high-fat meal conditions. No differences were found in SC401 DHA AUC 0-t (t = 24 hours) among the 3 conditions (91.69% high-fat/fasted, 97.12% low-fat/fasted, and 105.92% low-fat/high-fat; P > .05 in all cases). In contrast, SC401 EPA AUC 0-t was affected by food intake (179.06% high-fat/fasted, P food effect for DHA and partially ameliorated it for EPA. SC401 represents a convenient option for treatment of severe hypertriglyceridemia, especially for patients under a restricted intake of dietary fat. Copyright © 2017 National Lipid

  18. Docosahexaenoic fatty acid (DHA) in the regulation of colon cell growth and cell death: A review

    Czech Academy of Sciences Publication Activity Database

    Skender, Belma; Vaculová, Alena; Hofmanová, Jiřina

    2012-01-01

    Roč. 156, č. 3 (2012), s. 186-199 ISSN 1213-8118 R&D Projects: GA ČR(CZ) GD303/09/H048; GA ČR(CZ) GAP301/11/1730 Institutional research plan: CEZ:AV0Z50040702 Keywords : polyunsaturated fatty acids * colon cancer * apoptosis Subject RIV: BO - Biophysics Impact factor: 0.990, year: 2012

  19. Arginyl-glutamine dipeptide or docosahexaenoic acid attenuates hyperoxia-induced small intestinal injury in neonatal mice.

    Science.gov (United States)

    Li, Nan; Ma, Liya; Liu, Xueyan; Shaw, Lynn; Li Calzi, Sergio; Grant, Maria B; Neu, Josef

    2012-04-01

    Supplementation studies of glutamine, arginine, and docosahexaenoic acid (DHA) have established the safety of each of these nutrients in neonates; however, the potential for a more stable and soluble dipeptide, arginyl-glutamine (Arg-Gln) or DHA with anti-inflammatory properties, to exert benefits on hyperoxia-induced intestinal injury has not been investigated. Arg-Gln dipeptide has been shown to prevent retinal damage in a rodent model of oxygen-induced injury. The objective of the present study was to investigate whether Arg-Gln dipeptide or DHA could also attenuate markers of injury and inflammation to the small intestine in this same model. Seven-day-old mouse pups were placed with their dams in 75% oxygen for 5 days. After 5 days of hyperoxic exposure (P7-P12), pups were removed from hyperoxia and allowed to recover in atmospheric conditions for 5 days (P12-P17). Mouse pups received Arg-Gln (5g·kg·day) or DHA (5g·kg·day) or vehicle orally started on P12 through P17. Distal small intestine (DSI) histologic changes, myeloperoxidase (MPO), lactate dehydrogenase (LDH), inflammatory cytokines, and tissue apoptosis were evaluated. Hyperoxic mice showed a greater distortion of overall villus structure and with higher injury score (PDHA supplementation groups were more similar to the room air control group. Supplementation of Arg-Gln or DHA reduced hyperoxia-induced MPO activity (PDHA returned LDH activity to the levels of control. Hyperoxia induced apoptotic cell death in DSIs, and both Arg-Gln and DHA reversed this effect (PDHA may limit some inflammatory and apoptotic processes involved in hyperoxic-induced intestinal injury in neonatal mice.

  20. Effect of Docosahexaenoic Acid (DHA) Supplementation on Inflammatory Cytokine Levels in Infants at High Genetic Risk for Type 1 Diabetes

    Science.gov (United States)

    Chase, H. Peter; Boulware, David; Rodriguez, Henry; Donaldson, David; Chritton, Sonia; Rafkin-Mervis, Lisa; Krischer, Jeffrey; Skyler, Jay S.; Clare-Salzler, Michael

    2014-01-01

    OBJECTIVE Type 1 diabetes (T1D) results from the inflammatory destruction of pancreatic β-cells. In the present study, we investigated the effect of docosahexaenoic acid (DHA) supplementation on stimulated inflammatory cytokine production in white blood cells (WBC) from infants with a high genetic risk for T1D. RESEARCH DESIGN AND METHODS This was a multicenter, two-arm, randomized, double blind pilot trial of DHA supplementation, beginning either in the last trimester of pregnancy (41 infants) or in the first five months after birth (57 infants). Levels of DHA in infant and maternal red blood cell (RBC) membranes and in breast milk were analyzed by gas chromatography/mass spectrometry. Inflammatory cytokines were assayed from whole blood culture supernatants using the Luminex Multiplex assay after stimulation with high dose lipopolysaccharide (LPS), 1μg/mL. RESULTS The levels of RBC DHA were increased by 61–100% in treated compared to control infants at ages 6 to 36 months. There were no statistically significant reductions in production of the inflammatory cytokines, IL-1β, TNFα or IL-12p40 at any of the 6 time points measured. The inflammatory marker, hsCRP, was significantly lower in breast-fed DHA-treated infants compared to all formula-fed infants at age 12 months. Three infants (two received DHA) were removed from the study as a result of developing ≥ two persistently positive biochemical islet autoantibodies. CONCLUSIONS This pilot trial showed that supplementation of infant diets with DHA is safe and fulfilled the pre-study goal of increasing infant RBC DHA levels by at least 20%. Inflammatory cytokine production was not consistently reduced. PMID:25039804

  1. Effect of docosahexaenoic acid supplementation on inflammatory cytokine levels in infants at high genetic risk for type 1 diabetes.

    Science.gov (United States)

    Chase, H Peter; Boulware, David; Rodriguez, Henry; Donaldson, David; Chritton, Sonia; Rafkin-Mervis, Lisa; Krischer, Jeffrey; Skyler, Jay S; Clare-Salzler, Michael

    2015-06-01

    Type 1 diabetes (T1D) results from the inflammatory destruction of pancreatic β-cells. In this study, we investigated the effect of docosahexaenoic acid (DHA) supplementation on stimulated inflammatory cytokine production in white blood cells (WBC) from infants with a high genetic risk for T1D. This was a multicenter, two-arm, randomized, double-blind pilot trial of DHA supplementation, beginning either in the last trimester of pregnancy (41 infants) or in the first 5 months after birth (57 infants). Levels of DHA in infant and maternal red blood cell (RBC) membranes and in breast milk were analyzed by gas chromatography/mass spectrometry. Inflammatory cytokines were assayed from whole blood culture supernatants using the Luminex multiplex assay after stimulation with high dose lipopolysaccharide (LPS), 1 µg/mL. The levels of RBC DHA were increased by 61-100% in treated compared to control infants at ages 6-36 months. There were no statistically significant reductions in production of the inflammatory cytokines, IL-1β, TNFα, or IL-12p40 at any of the six timepoints measured. The inflammatory marker, high-sensitivity C-reactive protein (hsCRP), was significantly lower in breast-fed DHA-treated infants compared to all formula-fed infants at the age of 12 months. Three infants (two received DHA) were removed from the study as a result of developing ≥two persistently positive biochemical islet autoantibodies. This pilot trial showed that supplementation of infant diets with DHA is safe and fulfilled the pre-study goal of increasing infant RBC DHA levels by at least 20%. Inflammatory cytokine production was not consistently reduced. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Acute treatment with docosahexaenoic acid complexed to albumin reduces injury after a permanent focal cerebral ischemia in rats.

    Directory of Open Access Journals (Sweden)

    Tiffany N Eady

    Full Text Available Docosahexaenoic acid complexed to albumin (DHA-Alb is highly neuroprotective after temporary middle cerebral artery occlusion (MCAo, but whether a similar effect occurs in permanent MCAo is unknown. Male Sprague-Dawley rats (270-330 g underwent permanent MCAo. Neurological function was evaluated on days 1, 2 and 3 after MCAo. We studied six groups: DHA (5 mg/kg, Alb (0.63 or 1.25 g/kg, DHA-Alb (5 mg/kg+0.63 g/kg or 5 mg/kg+1.25 g/kg or saline. Treatment was administered i.v. at 3 h after onset of stroke (n = 7-10 per group. Ex vivo imaging of brains and histopathology were conducted on day 3. Saline- and Alb-treated rats developed severe neurological deficits but were not significantly different from one another. In contrast, rats treated with low and moderate doses of DHA-Alb showed improved neurological score compared to corresponding Alb groups on days 2 and 3. Total, cortical and subcortical lesion volumes computed from T2 weighted images were reduced following a moderate dose of DHA-Alb (1.25 g/kg by 25%, 22%, 34%, respectively, compared to the Alb group. The total corrected, cortical and subcortical infarct volumes were reduced by low (by 36-40% and moderate doses (by 34-42% of DHA-Alb treatment compared to the Alb groups. In conclusion, DHA-Alb therapy is highly neuroprotective in permanent MCAo in rats. This treatment can provide the basis for future therapeutics for patients suffering from ischemic stroke.

  3. Docosahexaenoic acid inhibits IL-6 expression via PPARγ-mediated expression of catalase in cerulein-stimulated pancreatic acinar cells.

    Science.gov (United States)

    Song, Eun Ah; Lim, Joo Weon; Kim, Hyeyoung

    2017-07-01

    Cerulein pancreatitis mirrors human acute pancreatitis. In pancreatic acinar cells exposed to cerulein, reactive oxygen species (ROS) mediate inflammatory signaling by Janus kinase (JAK) 2/signal transducer and activator of transcription (STAT) 3, and cytokine induction. Docosahexaenoic acid (DHA) acts as an agonist of peroxisome proliferator activated receptor γ (PPARγ), which mediates the expression of some antioxidant enzymes. We hypothesized that DHA may induce PPARγ-target catalase expression and reduce ROS levels, leading to the inhibition of JAK2/STAT3 activation and IL-6 expression in cerulein-stimulated acinar cells. Pancreatic acinar AR42J cells were treated with DHA in the presence or absence of the PPARγ antagonist GW9662, or treated with the PPARγ agonist troglitazone, and then stimulated with cerulein. Expression of IL-6 and catalase, ROS levels, JAK2/STAT3 activation, and nuclear translocation of PPARγ were assessed. DHA suppressed the increase in ROS, JAK2/STAT3 activation, and IL-6 expression induced nuclear translocation of PPARγ and catalase expression in cerulein-stimulated AR42J cells. Troglitazone inhibited the cerulein-induced increase in ROS and IL-6 expression, but induced catalase expression similar to DHA in AR42J cells. GW9662 abolished the inhibitory effect of DHA on cerulein-induced increase in ROS and IL-6 expression in AR42J cells. DHA-induced expression of catalase was suppressed by GW9662 in cerulein-stimulated AR42J cells. Thus, DHA induces PPARγ activation and catalase expression, which inhibits ROS-mediated activation of JAK2/STAT3 and IL-6 expression in cerulein-stimulated pancreatic acinar cells. Copyright © 2017. Published by Elsevier Ltd.

  4. Long-Term Effect of Docosahexaenoic Acid Feeding on Lipid Composition and Brain Fatty Acid-Binding Protein Expression in Rats

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    Marwa E. Elsherbiny

    2015-10-01

    Full Text Available Arachidonic (AA and docosahexaenoic acid (DHA brain accretion is essential for brain development. The impact of DHA-rich maternal diets on offspring brain fatty acid composition has previously been studied up to the weanling stage; however, there has been no follow-up at later stages. Here, we examine the impact of DHA-rich maternal and weaning diets on brain fatty acid composition at weaning and three weeks post-weaning. We report that DHA supplementation during lactation maintains high DHA levels in the brains of pups even when they are fed a DHA-deficient diet for three weeks after weaning. We show that boosting dietary DHA levels for three weeks after weaning compensates for a maternal DHA-deficient diet during lactation. Finally, our data indicate that brain fatty acid binding protein (FABP7, a marker of neural stem cells, is down-regulated in the brains of six-week pups with a high DHA:AA ratio. We propose that elevated levels of DHA in developing brain accelerate brain maturation relative to DHA-deficient brains.

  5. The role of omega-3 polyunsaturated fatty acids eicosapentaenoic and docosahexaenoic acids in the treatment of major depression and Alzheimer's disease: Acting separately or synergistically?

    Science.gov (United States)

    Song, Cai; Shieh, Chu-Hsin; Wu, Yi-Shyuan; Kalueff, Allan; Gaikwad, Siddharth; Su, Kuan-Pin

    2016-04-01

    Omega-3 polyunsaturated fatty acids (n-3-PUFAs), mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may improve or prevent some psychiatric and neurodegenerative diseases in both experimental and clinical studies. As important membrane components, these PUFAs benefit brain health by modulating neuroimmune and apoptotic pathways, changing membrane function and/or competing with n-6 PUFAs, the precursors of inflammatory mediators. However, the exact role of each fatty acid in neuroimmune modulation and neurogenesis, the interaction between EPA and DHA, and the best EPA:DHA ratios for improving brain disorders, remain unclear. It is also unknown whether EPA, as a DHA precursor, acts directly or via DHA. Here, we discuss recent evidence of EPA and DHA effects in the treatment of major depression and Alzheimer's disease, as well as their potential synergistic action on anti-inflammatory, antioxidant and neurotrophic processes in the brain. We further analyze the cellular and molecular mechanisms by which EPA, DHA or their combination may benefit these diseases. We also outline the limitations of current studies and suggest new genetic models and novel approaches to overcome these limitations. Finally, we summarize future strategies for translational research in this field. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Modification of Docosahexaenoic Acid Composition of Milk from Nursing Women Who Received Alpha Linolenic Acid from Chia Oil during Gestation and Nursing

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    Rodrigo Valenzuela

    2015-08-01

    Full Text Available α-Linolenic acid (ALA is the precursor of docosahexaenoic acid (DHA in humans, which is fundamental for brain and visual function. Western diet provides low ALA and DHA, which is reflected in low DHA in maternal milk. Chia oil extracted from chia (Salvia hispanica L., a plant native to some Latin American countries, is high in ALA (up to 60% and thereby is an alternative to provide ALA with the aim to reduce DHA deficits. We evaluated the modification of the fatty acid profile of milk obtained from Chilean mothers who received chia oil during gestation and nursing. Forty healthy pregnant women (22–35 years old tabulated for food consumption, were randomly separated into two groups: a control group with normal feeding (n = 21 and a chia group (n = 19, which received 16 mL chia oil daily from the third trimester of pregnancy until the first six months of nursing. The fatty acid profile of erythrocyte phospholipids, measured at six months of pregnancy, at time of delivery and at six months of nursing, and the fatty acid profile of the milk collected during the first six months of nursing were assessed by gas-chromatography. The chia group, compared to the control group, showed (i a significant increase in ALA ingestion and a significant reduction of linoleic acid (LA ingestion, no showing modification of arachidonic acid (AA, eicosapentaenoic acid (EPA and DHA; (ii a significant increase of erythrocyte ALA and EPA and a reduction of LA. AA and DHA were not modified; (iii a increased milk content of ALA during the six months of nursing, whereas LA showed a decrease. AA and EPA were not modified, however DHA increased only during the first three months of nursing. Consumption of chia oil during the last trimester of pregnancy and the first three months of nursing transiently increases the milk content of DHA.

  7. How dietary arachidonic- and docosahexaenoic- acid rich oils differentially affect the murine hepatic transcriptome

    OpenAIRE

    Roberts Matthew A; Berger Alvin; Hoff Bruce

    2006-01-01

    Introduction Herein, we expand our previous work on the effects of long chain polyunsaturated fatty acids (LC-PUFA) on the murine hepatic transcriptome using novel statistical and bioinformatic approaches for evaluating microarray data. The analyses focuses on key differences in the transcriptomic response that will influence metabolism following consumption of FUNG (rich in 20:4n6), FISH (rich in 20:5n3, 22:5n3, and 22:6n3) and COMB, the combination of the two. Results Using a variance-stab...

  8. The effect of conjugated linoleic acid on the fatty acid composition of ...

    African Journals Online (AJOL)

    The effect of conjugated linoleic acid on the fatty acid composition of different tissues and yolk lipids in pigeons. ... South African Journal of Animal Science ... Eight established breeding pairs per group were fed either a commercially pelleted pigeon diet mixed with 0.5% safflower oil (SFO) or 0.5% CLA for 12 weeks. For fatty ...

  9. Meat quality and tissue fatty acid profiles in rabbits fed diets supplemented with conjugated linoleic acid

    Czech Academy of Sciences Publication Activity Database

    Marounek, Milan; Skřivanová, V.; Dokoupilová, A.; Czauderna, M.; Berladyn, A.

    2007-01-01

    Roč. 52, č. 12 (2007), s. 552-561 ISSN 0375-8427 Institutional research plan: CEZ:AV0Z50450515 Keywords : rabbits * conjugated linoleic acid * fatty acids Subject RIV: GH - Livestock Nutrition Impact factor: 0.645, year: 2007

  10. Effects of Short-Term Docosahexaenoic Acid Supplementation on Markers of Inflammation after Eccentric Strength Exercise in Women

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    Katherine E. Corder, Katherine R. Newsham, Jennifer L. McDaniel, Uthayashanker R. Ezekiel, Edward P. Weiss

    2016-03-01

    Full Text Available The omega-3 fatty acid docosahexaenoic acid (DHA has anti-inflammatory and anti-nociceptive (pain inhibiting effects. Because strenuous exercise often results in local inflammation and pain, we hypothesized that DHA supplementation attenuates the rise in markers of local muscle inflammation and delayed onset muscle soreness (DOMS that occur after eccentric strength exercise. Twenty-seven, healthy women (33 ± 2 y, BMI 23.1±1.0 kg·m-2 were randomized to receive 9d of 3000 mg/d DHA or placebo in a double-blind fashion. On day 7 of the supplementation period, the participants performed 4 sets of maximal-effort eccentric biceps curl exercise. Before and 48h after the eccentric exercise, markers of inflammation were measured including measures of muscle soreness (10-point visual analog pain scale, VAS, swelling (arm circumference, muscle stiffness (active and passive elbow extension, skin temperature, and salivary C-reactive protein (CRP concentrations. As expected, muscle soreness and arm circumference increased while active and passive elbow extension decreased. The increase in soreness was 23% less in the DHA group (48h increase in VAS soreness ratings: 4.380.4 vs. 5.600.5, p=0.02. Furthermore, the number of subjects who were able to achieve full active elbow extension 48h after eccentric exercise was greater in the DHA group (71% vs. 15%, p = 0.006, indicating significantly less muscle stiffness. No between-group differences were observed for passive elbow extension (p = 0.78 or arm swelling (p = 0.75. Skin temperature and salivary CRP concentrations did not change from baseline to 48h after exercise in either group. These findings indicate that short-term DHA supplementation reduces exercise-induced muscle soreness and stiffness. Therefore, in addition to other health benefits that n-3 fatty acids have been associated with, DHA supplementation could be beneficial for improving tolerance to new and/or strenuous exercise programs and thereby

  11. Astaxanthin and Docosahexaenoic Acid Reverse the Toxicity of the Maxi-K (BK Channel Antagonist Mycotoxin Penitrem A

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    Amira A. Goda

    2016-11-01

    Full Text Available Penitrem A (PA is a food mycotoxin produced by several terrestrial and few marine Penicillium species. PA is a potent tremorgen through selective antagonism of the calcium-dependent potassium BK (Maxi-K channels. Discovery of natural products that can prevent the toxic effects of PA is important for food safety. Astaxanthin (AST is a marine natural xanthophyll carotenoid with documented antioxidant activity. Unlike other common antioxidants, AST can cross blood brain barriers (BBBs, inducing neuroprotective effects. Docosahexaenoic acid (DHA is polyunsaturated ω-3 fatty acid naturally occurring in fish and algae. DHA is essential for normal neurological and cellular development. This study evaluated the protective activity of AST and DHA against PA-induced toxicity, in vitro on Schwann cells CRL-2765 and in vivo in the worm Caenorhbitidis elegans and Sprague Dawley rat models. PA inhibited the viability of Schwann cells, with an IC50 of 22.6 μM. Dose-dependent treatments with 10–100 μM DHA significantly reversed the PA toxicity at its IC50 dose, and improved the survival of Schwann cells to 70.5%–98.8%. Similarly, dose-dependent treatments with 10–20 μM AST reversed the PA toxicity at its IC50 dose and raised these cells’ survival to 61.7%–70.5%. BK channel inhibition in the nematode C. elegans is associated with abnormal reversal locomotion. DHA and AST counteracted the in vivo PA BK channel antagonistic activity in the C. elegans model. Rats fed a PA-contaminated diet showed high levels of glutamate (GLU, aspartate (ASP, and gamma amino butyric acid (GABA, with observed necrosis or absence of Purkinjie neurons, typical of PA-induced neurotoxicity. Dopamine (DA, serotonin (5-HT, and norepinephrine (NE levels were abnormal, Nitric Oxide (NO and Malondialdehyde (MDA levels were significantly increased, and total antioxidant capacity (TAC level in serum and brain homogenates was significantly decreased in PA-treated rats. DHA and AST

  12. Oral docosahexaenoic acid in the prevention of exudative age-related macular degeneration: the Nutritional AMD Treatment 2 study.

    Science.gov (United States)

    Souied, Eric H; Delcourt, Cécile; Querques, Giuseppe; Bassols, Ana; Merle, Bénédicte; Zourdani, Alain; Smith, Theodore; Benlian, Pascale

    2013-08-01

    To evaluate the efficacy of docosahexaenoic acid (DHA)-enriched oral supplementation in preventing exudative age-related macular degeneration (AMD). The Nutritional AMD Treatment 2 study was a randomized, placebo-controlled, double-blind, parallel, comparative study. Two hundred sixty-three patients 55 years of age or older and younger than 85 years with early lesions of age-related maculopathy and visual acuity better than 0.4 logarithm of minimum angle of resolution units in the study eye and neovascular AMD in the fellow eye. Patients were assigned randomly to receive either 840 mg/day DHA and 270 mg/day eicosapentaenoic acid (EPA) from fish oil capsules or the placebo (olive oil capsules) for 3 years. The primary outcome measure was time to occurrence of choroidal neovascularization (CNV) in the study eye. Secondary outcome measures in the study eye were: incidence of CNV developing in patients, changes in visual acuity, occurrence and progression of drusen, and changes in EPA plus DHA level in red blood cell membrane (RBCM). Time to occurrence and incidence of CNV in the study eye were not significantly different between the DHA group (19.5±10.9 months and 28.4%, respectively) and the placebo group (18.7±10.6 months and 25.6%, respectively). In the DHA group, EPA plus DHA levels increased significantly in RBCM (+70%; P<0.001), suggesting that DHA easily penetrated cells, but this occurred unexpectedly also in the placebo group (+9%; P = 0.007). In the DHA-allocated group, patients steadily achieving the highest tertile of EPA plus DHA levels in RBCM had significantly lower risk (-68%; P = 0.047; hazard ratio, 0.32; 95% confidence interval, 0.10-0.99) of CNV developing over 3 years. No marked changes from baseline in best-corrected visual acuity, drusen progression, or geographic atrophy in the study eye were observed throughout the study in either group. In patients with unilateral exudative AMD, 3 years of oral DHA-enriched supplementation had the same

  13. Eicosapentaenoic and docosahexaenoic acids enriched polyunsaturated fatty acids from the coastal marine fish of Bay of Bengal and their therapeutic value.

    Science.gov (United States)

    Bera, Rabindranath; Dhara, Tushar K; Bhadra, Ranjan; Majumder, Gopal C; Sen, Parimal C

    2010-12-01

    Eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) enriched polyunsaturated fatty acids (PUFA) significantly present in marine fish oil emerge as preventive agents for combating many health problems specially in chronic or metabolic disorders. The fish in the coastal area of Bay of Bengal has remained unexplored with respect to EPA/DHA enriched PUFA content in its oils, although it may be a potential source in harnessing the health benefit. In this study, seven varieties of the coastal fish were analysed for the content of EPA/DHA. The one locally known as lotte, (Harpadon nehereus) though has low content of total lipids, was found to have high EPA/DHA in its oil. The phospholipids rich fraction was extracted from the total fish oil. The EPA/DHA enriched PUFA was isolated to investigate the potential use for health benefits. EPA/DHA is found to act as protective agent against mercury poisoning studied in cell culture as well as in animal mode. It is found to be highly preventive in diabetes. The lotte is available in the coastal area of Bay of Bengal adjoining West Bengal, India in large scale and it is the first report showing EPA/DHA enriched PUFA in these fish oil that can be availed to harness in important health benefits.

  14. Use of radiolabeled substrates to determine the desaturase and elongase activities involved in eicosapentaenoic acid and docosahexaenoic acid biosynthesis in the marine microalga Pavlova lutheri.

    Science.gov (United States)

    Guihéneuf, Freddy; Ulmann, Lionel; Mimouni, Virginie; Tremblin, Gérard

    2013-06-01

    The marine flagellate Pavlova lutheri is a microalga known to be rich in long-chain polyunsaturated fatty acids (LC-PUFAs) and able to produce large amounts of n-3 fatty acids, such as eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3). As no previous study had attempted to measure the metabolic step of fatty acid synthesis in this alga, we used radiolabeled precursors to explore the various desaturation and elongation steps involved in LC-PUFA biosynthesis pathways. The incorporation of (14)C-labeled palmitic ([1-(14)C] 16:0) and dihomo-γ-linolenic ([1-(14)C] 20:3n-6) acids as ammonium salts within the cells was monitored during incubation periods lasting 3, 10 or 24h. Total lipids and each of the fatty acids were also monitored during these incubation periods. A decrease in the availability and/or accessibility of the radiolabeled substrates was observed over the incubation time. This decrease with incubation time observed using [1-(14)C] 16:0 and [1-(14)C] 20:3n-6 as substrates was used to monitor the conversion of (14)C-labeled arachidonic acid ([1-(14)C] 20:4n-6) into longer and more unsaturated fatty acids, such as 20:5n-3 and 22:6n-3, over shorter incubation times (1 and 3h). A metabolic relationship between the n-6 and n-3 fatty acid series was demonstrated in P. lutheri by measuring the Δ17-desaturation activity involved in the conversion of eicosatetraenoic acid to 20:5n-3. Our findings suggest that the biosynthesis pathway leading to n-3 LC-PUFA involves fatty acids of the n-6 family, which act as precursors in the biosynthesis of 20:5n-3 and 22:6n-3. This preliminary work provides a method for studying microalgal LC-PUFA biosynthesis pathways and desaturase and elongase activities in vivo using externally-radiolabeled fatty acid precursors as substrates. The use of the [1-(14)C] 20:4n-6 substrate also highlighted the relationships between the n-6 and the n-3 fatty acid series (e.g. Δ17-desaturation), and the final elongation

  15. Regulation of Serum Response Factor and Adiponectin by PPARγ Agonist Docosahexaenoic Acid

    Directory of Open Access Journals (Sweden)

    Clayton Johnson

    2011-01-01

    Full Text Available Recent studies indicate that significant health benefits involving the regulation of signaling proteins result from the consumption of omega-3 polyunsaturated fatty acids (ω-3 PUFAs. Serum response factor (SRF is involved in transcriptional regulation of muscle growth and differentiation. SRF levels are increased in the aging heart muscle. It has not been examined whether SRF is made by adipocytes and whether SRF secretion by adipocytes is modulated by PPARγ agonist DHA. Adiponectin is made exclusively by adipocytes. We and others have previously reported that PUFAs such as DHA increase adiponectin levels and secretion in adipocytes. Here we show that DHA downregulates SRF with a simultaneous upregulation of adiponectin and that both these responses are reversible by PPARγ antagonist. Furthermore, there appears to be a direct relationship between DHA exposure and increased levels of membrane-associated high-density adiponectin, as well as lower levels of membrane-associated SRF. Thus, we find that the levels of SRF and adiponectin are inversely related in response to treatment with PPARγ agonist DHA. Decreased levels of SRF along with increase in membrane-associated adiponectin could in part mediate the health benefits of DHA.

  16. Compound-specific isotope analysis resolves the dietary origin of docosahexaenoic acid in the mouse brain.

    Science.gov (United States)

    Lacombe, R J Scott; Giuliano, Vanessa; Colombo, Stefanie M; Arts, Michael T; Bazinet, Richard P

    2017-10-01

    DHA (22:6n-3) may be derived from two dietary sources, preformed dietary DHA or through synthesis from α-linolenic acid (ALA; 18:3n-3). However, conventional methods cannot distinguish between DHA derived from either source without the use of costly labeled tracers. In the present study, we demonstrate the proof-of-concept that compound-specific isotope analysis (CSIA) by GC-isotope ratio mass spectrometry (IRMS) can differentiate between sources of brain DHA based on differences in natural 13 C enrichment. Mice were fed diets containing either purified ALA or DHA as the sole n-3 PUFA. Extracted lipids were analyzed by CSIA for natural abundance 13 C enrichment. Brain DHA from DHA-fed mice was significantly more enriched (-23.32‰ to -21.92‰) compared with mice on the ALA diet (-28.25‰ to -27.49‰). The measured 13 C enrichment of brain DHA closely resembled the dietary n-3 PUFA source, -21.86‰ and -28.22‰ for DHA and ALA, respectively. The dietary effect on DHA 13 C enrichment was similar in liver and blood fractions. Our results demonstrate the effectiveness of CSIA, at natural 13 C enrichment, to differentiate between the incorporation of preformed or synthesized DHA into the brain and other tissues without the need for tracers. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  17. How dietary arachidonic- and docosahexaenoic- acid rich oils differentially affect the murine hepatic transcriptome

    Directory of Open Access Journals (Sweden)

    Roberts Matthew A

    2006-04-01

    Full Text Available Introduction Herein, we expand our previous work on the effects of long chain polyunsaturated fatty acids (LC-PUFA on the murine hepatic transcriptome using novel statistical and bioinformatic approaches for evaluating microarray data. The analyses focuses on key differences in the transcriptomic response that will influence metabolism following consumption of FUNG (rich in 20:4n6, FISH (rich in 20:5n3, 22:5n3, and 22:6n3 and COMB, the combination of the two. Results Using a variance-stabilized F-statistic, 371 probe sets (out of 13 K probe sets in the Affymetrix Mu11K chip set were changed by dietary treatment (P Conclusion Distinct transcriptomic, signaling cascades, and predicted affects on murine liver metabolism have been elucidated for 20:4n6-rich dietary oils, 22:6n3-rich oils, and a surprisingly distinct set of genes were affected by the combination of the two. Our results emphasize that the balance of dietary n6 and n3 LC-PUFA provided for infants and in nutritional and neutraceutical applications could have profoundly different affects on metabolism and cell signaling, beyond that previously recognized.

  18. Characterization of synergistic anti-cancer effects of docosahexaenoic acid and curcumin on DMBA-induced mammary tumorigenesis in mice

    International Nuclear Information System (INIS)

    Siddiqui, Rafat A; Harvey, Kevin A; Walker, Candace; Altenburg, Jeffrey; Xu, Zhidong; Terry, Colin; Camarillo, Ignacio; Jones-Hall, Yava; Mariash, Cary

    2013-01-01

    The major obstacles to the successful use of individual nutritional compounds as preventive or therapeutic agents are their efficacy and bioavailability. One approach to overcoming this problem is to use combinations of nutrients to induce synergistic effects. The objective of this research was to investigate the synergistic effects of two dietary components: docosahexaenoic acid (DHA), an omega-3 fatty acid present in cold-water fish, and curcumin (CCM), an herbal nutrient present in turmeric, in an in vivo model of DMBA-induced mammary tumorigenesis in mice. We used the carcinogen DMBA to induce breast tumors in SENCAR mice on control, CCM, DHA, or DHA + CCM diets. Appearance and tumor progression were monitored daily. The tumors were harvested 15 days following their first appearance for morphological and immunohistological analysis. Western analysis was performed to determine expression of maspin and survivin in the tumor tissues. Characterization of tumor growth was analyzed using appropriate statistical methods. Otherwise all other results are reported as mean ± SD and analyzed with one-way ANOVA and Tukey’s post hoc procedure. Analysis of gene microarray data indicates that combined treatment with DHA + CCM altered the profile of “PAM50” genes in the SK-BR-3 cell line from an ER - /Her-2 + to that resembling a “normal-like” phenotype. The in vivo studies demonstrated that DHA + CCM treatment reduced the incidence of breast tumors, delayed tumor initiation, and reduced progression of tumor growth. Dietary treatment had no effect on breast size development, but tumors from mice on a control diet (untreated) were less differentiated than tumors from mice fed CCM or DHA + CCM diets. The synergistic effects also led to increased expression of the pro-apoptotic protein, maspin, but reduced expression of the anti-apoptotic protein, survivin. The SK-BR-3 cells and DMBA-induced tumors, both with an ER - and Her-2 + phenotype, were affected by the

  19. Radioimmunoassay of conjugated cholic acid, chenodeoxycholic acid, and deoxycholic acid from human serum, with use of 125I-labeled ligands

    International Nuclear Information System (INIS)

    Maeentausta, O.; Jaenne, O.

    1979-01-01

    We describe a method for radioimmunoassay of conjugated cholic acid, chenodeoxycholic acid, and deoxycholic acid in serum. In the method, 125 I-labeled bile acid conjugates are used as the tracers along with antibodies raised against individual bile acid-bovine serum albumin conjugates. Antibody-bound and free bile acids were separated by polyethylene glycol precipitation (final concentration, 125 g/L). The lowest measurable amounts of the bile acids, expressed as pmol/tube, were: cholic acid conjugates, 2; chenodeoxycholic acid conjugates, 0.5; and deoxycholic acid conjugates, 2. Analytical recovery of bile acids added to bile acid-free serum ranged from 85 to 110%; intra-assay and inter-assay CVs ranged from 8.3 to 5.3% and from 5.3 to 12.2%, respectively. Concentrations (mean +- SD) of the bile acid conjugates in serum from apparently healthy women and men (in μmol/L) were: cholic acid conjugates, 0.43 +- 0.17 (n=126); chenodeoxycholic acid conjugates, 0.47 +- 0.23 (n=111); and deoxycholic acid conjugates, 0.33 +- 0.11 (n=96). The values for primary bile acids were greatly increased in patients with various hepatobiliary diseases

  20. Docosapentaenoic acid and docosahexaenoic acid are positively associated with insulin sensitivity in rats fed high-fat and high-fructose diets.

    Science.gov (United States)

    Huang, Jiung-Pang; Cheng, Mei-Ling; Hung, Cheng-Yu; Wang, Chao-Hung; Hsieh, Po-Shiuan; Shiao, Ming-Shi; Chen, Jan-Kan; Li, Dai-Er; Hung, Li-Man

    2017-10-01

    The aim of the present study was to compare insulin resistance and metabolic changes using a global lipidomic approach. Rats were fed a high-fat diet (HFD) or a high-fructose diet (HFrD) for 12 weeks to induce insulin resistance (IR) syndrome. After 12 weeks feeding, physiological and biochemical parameters were examined. Insulin sensitivity and plasma metabolites were evaluated using a euglycemic-hyperinsulinemic clamp and mass spectrometry, respectively. Pearson's correlation coefficient was used to investigate the strength of correlations. Rats on both diets developed IR syndrome, characterized by hypertension, hyperlipidemia, hyperinsulinemia, impaired fasting glucose, and IR. Compared with HFrD-fed rats, non-esterified fatty acids were lower and body weight and plasma insulin levels were markedly higher in HFD-fed rats. Adiposity and plasma leptin levels were increased in both groups. However, the size of adipocytes was greater in HFD- than HFrD-fed rats. Notably, the lipidomic heat map revealed metabolites exhibiting greater differences in HFD- and HFrD-fed rats compared with controls. Plasma adrenic acid levels were higher in HFD- than HFrD-fed rats. Nevertheless, linoleic and arachidonic acid levels decreased in HFrD-fed rats compared with controls. Plasma concentrations of docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) were significantly reduced after feeding of both diets, particularly the HFrD. There was a strong positive correlation between these two fatty acids and the insulin sensitivity index. The systemic lipidomic analysis indicated that a reduction in DHA and DPA was strongly correlated with IR in rats under long-term overnutrition. These results provide a potential therapeutic target for IR and metabolic syndrome. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  1. Dynamical Approach to Multiequilibria Problems for Mixtures of Acids and Their Conjugated Bases

    Science.gov (United States)

    Glaser, Rainer E.; Delarosa, Marco A.; Salau, Ahmed Olasunkanmi; Chicone, Carmen

    2014-01-01

    Mathematical methods are described for the determination of steady-state concentrations of all species in multiequilibria systems consisting of several acids and their conjugated bases in aqueous solutions. The main example consists of a mixture of a diprotic acid H[subscript 2]A, a monoprotic acid HB, and their conjugate bases. The reaction…

  2. Chemopreventive and renal protective effects for docosahexaenoic acid (DHA: implications of CRP and lipid peroxides

    Directory of Open Access Journals (Sweden)

    Darweish MM

    2009-04-01

    Full Text Available Abstract Background The fish oil-derived ω-3 fatty acids, like docosahexanoic (DHA, claim a plethora of health benefits. We currently evaluated the antitumor effects of DHA, alone or in combination with cisplatin (CP in the EAC solid tumor mice model, and monitored concomitant changes in serum levels of C-reactive protein (CRP, lipid peroxidation (measured as malondialdehyde; MDA and leukocytic count (LC. Further, we verified the capacity of DHA to ameliorate the lethal, CP-induced nephrotoxicity in rats and the molecular mechanisms involved therein. Results EAC-bearing mice exhibited markedly elevated LC (2-fold, CRP (11-fold and MDA levels (2.7-fold. DHA (125, 250 mg/kg elicited significant, dose-dependent reductions in tumor size (38%, 79%; respectively, as well as in LC, CRP and MDA levels. These effects for CP were appreciably lower than those of DHA (250 mg/kg. Interestingly, DHA (125 mg/kg markedly enhanced the chemopreventive effects of CP and boosted its ability to reduce serum CRP and MDA levels. Correlation studies revealed a high degree of positive association between tumor growth and each of CRP (r = 0.85 and leukocytosis (r = 0.89, thus attesting to a diagnostic/prognostic role for CRP. On the other hand, a single CP dose (10 mg/kg induced nephrotoxicity in rats that was evidenced by proteinuria, deterioration of glomerular filtration rate (GFR, -4-fold, a rise in serum creatinine/urea levels (2–5-fold after 4 days, and globally-induced animal fatalities after 7 days. Kidney-homogenates from CP-treated rats displayed significantly elevated MDA- and TNF-α-, but reduced GSH-, levels. Rats treated with DHA (250 mg/kg, but not 125 mg/kg survived the lethal effects of CP, and showed a significant recovery of GFR; while their homogenates had markedly-reduced MDA- and TNF-α-, but -increased GSH-levels. Significant association was detected between creatinine level and those of MDA (r = 0.81, TNF-α r = 0.92 and GSH (r = -0

  3. Docosahexaenoic Acid Modulates a HER2-Associated Lipogenic Phenotype, Induces Apoptosis, and Increases Trastuzumab Action in HER2-Overexpressing Breast Carcinoma Cells

    OpenAIRE

    Ravacci, Graziela Rosa; Brentani, Maria Mitzi; Tortelli, Tharcisio Citrângulo; Torrinhas, Raquel Suzana M. M.; Santos, Jéssica Reis; Logullo, Angela Flávia; Waitzberg, Dan Linetzky

    2015-01-01

    In breast cancer, lipid metabolic alterations have been recognized as potential oncogenic stimuli that may promote malignancy. To investigate whether the oncogenic nature of lipogenesis closely depends on the overexpression of HER2 protooncogene, the normal breast cell line, HB4a, was transfected with HER2 cDNA to obtain HER2-overexpressing HB4aC5.2 cells. Both cell lines were treated with trastuzumab and docosahexaenoic acid. HER2 overexpression was accompanied by an increase in the expressi...

  4. Oleic acid and docosahexaenoic acid cause an increase in the paracellular absorption of hydrophilic compounds in an experimental model of human absorptive enterocytes

    International Nuclear Information System (INIS)

    Aspenstroem-Fagerlund, Bitte; Ring, Linda; Aspenstroem, Pontus; Tallkvist, Jonas; Ilbaeck, Nils-Gunnar; Glynn, Anders W.

    2007-01-01

    Surface active compounds present in food possibly have the ability to enhance the absorption of water soluble toxic agents. Therefore, we investigated whether fatty acids such as oleic acid and docosahexaenoic acid (DHA), both commonly present in food, negatively affect the integrity of tight junctions (TJ) in the intestinal epithelium and thereby increase the absorption of poorly absorbed hydrophilic substances. Caco-2 cells, which are derived from human absorptive enterocytes, were grown on permeable filters for 20-25 days. Differentiated cell monolayers were apically exposed for 90 min to mannitol in emulsions of oleic acid (5, 15 or 30 mM) or DHA (5, 15 or 30 mM) in an experimental medium with or without Ca 2+ and Mg 2+ . Absorption of 14 C-mannitol increased and trans-epithelial electrical resistance (TEER) decreased in cell monolayers exposed to oleic acid and DHA, compared to controls. Cytotoxicity, measured as leakage of LDH, was higher in groups exposed to 30 mM oleic acid and all concentrations of DHA. Morphology of the cell monolayers was studied by using fluorescence microscopy. Exposure of cell monolayers to 5 mM DHA for 90 min resulted in a profound alteration of the cell-cell contacts as detected by staining the cells for β-catenin. Oleic acid (30 mM) treatment also induced dissolution of the cell-cell contacts but the effect was not as pronounced as with DHA. Cell monolayers were also exposed for 180 min to 250 nM cadmium (Cd) in emulsions of oleic acid (5 or 30 mM) or DHA (1 or 5 mM), in an experimental medium with Ca 2+ and Mg 2+ . Retention of Cd in Caco-2 cells was higher after exposure to 5 mM oleic acid but lower after exposure to 30 mM oleic acid and DHA. Absorption of Cd through the monolayers increased after DHA exposure but not after exposure to oleic acid. Our results indicate that fatty acids may compromise the integrity of the intestinal epithelium and that certain lipids in food may enhance the paracellular absorption of poorly

  5. Conjugated Linoleic Triacylglycerols Exhibit Superior Lymphatic Absorption Than Free Conjugate Linoleic Acids and Have Antiobesity Properties.

    Science.gov (United States)

    Woo, Hyunjoon; Chung, Min-Yu; Kim, Juyeon; Kong, Daecheol; Min, Jinyoung; Choi, Hee-Don; Choi, In-Wook; Kim, In-Hwan; Noh, Sang K; Kim, Byung Hee

    2016-05-01

    This study aimed to compare lymphatic absorption of conjugated linoleic acids (CLAs) in the triacylglycerol (TAG) or free fatty acid (FFA) form and to examine the antiobesity effects of different doses of CLAs in the TAG form in animals. Conjugated linoleic TAGs (containing 70.3 wt% CLAs; CLA-TAG) were prepared through lipase-catalyzed esterification of glycerol with commercial CLA mixtures (CLA-FFA). Lymphatic absorption of CLA-TAG and CLA-FFA was compared in a rat model of lymphatic cannulation. Greater amounts of cis-9,trans-11 and trans-10,cis-12 CLAs were detected in the collected lymph from a lipid emulsion containing CLA-TAG. This result suggests that CLA-TAG has greater capacity for lymphatic absorption than does CLA-FFA. The antiobesity efficacy of CLA-TAG at different doses was examined in mice with diet-induced obesity. A high-fat diet (HFD) for 12 weeks caused a significant increase in body weight and epididymal and retroperitoneal fat weights, which were significantly decreased by 2% dietary supplementation (w/w) with CLA-TAG. CLA-TAG at 2% significantly attenuated the HFD-induced upregulation of serum TAG, but led to hepatomegaly and exacerbated HFD-induced hypercholesterolemia. CLA-TAG at 1% significantly attenuated upregulation of retroperitoneal fat weight and significantly increased liver weight, which was decreased by the HFD. Nonetheless, the liver weight in group "HFD +1% CLA-TAG" was not significantly different from that of normal diet controls. CLA-TAG at 1% significantly reduced serum TAG levels and did not exacerbate HFD-induced hypercholesterolemia. Thus, 1% dietary supplementation with CLA-TAG reduces retroperitoneal fat weight without apparent hepatomegaly, a known side-effect of CLAs in mouse models of obesity.

  6. Omega-3 polyunsaturated fatty acid docosahexaenoic acid and its role in exhaustive-exercise-induced changes in female rat ovulatory cycle.

    Science.gov (United States)

    Mostafa, Abeer F; Samir, Shereen M; Nagib, R M

    2018-04-01

    Exhaustive exercises can cause delayed menarche or menstrual cycle irregularities in females. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are incorporated into a wide range of benefits in many physiological systems. Our work aimed to assess the role of ω-3 PUFA docosahexaenoic acid (DHA) on the deleterious effects of exhaustive exercise on the female reproductive system in rats. Virgin female rats were randomly divided into 4 groups (12 rats in each): control group, omega-3 group treated with DHA, exhaustive exercise group, and exhaustive exercised rats treated with DHA. Omega-3 was given orally to the rats once daily for 4 estrous cycles. Exhaustive exercises revealed lower levels in progesterone and gonadotropins together with histopathological decrease in number of growing follicles and corpora lutea. Moreover, the exercised rats showed low levels of ovarian antioxidants with high level of caspase-3 and plasma cortisol level that lead to disruption of hypothalamic-pituitary-gonadal axis. ω-3 PUFA DHA has beneficial effects on the number of newly growing follicles in both sedentary and exercised rats with decreasing the level of caspase-3 and increasing the antioxidant activity in ovaries. Exhaustive exercises can cause ovulatory problems in female rats that can be improved by ω-3 supplementation.

  7. A Study of the Differential Effects of Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) on Gene Expression Profiles of Stimulated Thp-1 Macrophages.

    Science.gov (United States)

    Allam-Ndoul, Bénédicte; Guénard, Frédéric; Barbier, Olivier; Vohl, Marie-Claude

    2017-04-25

    Background: An appropriate intake of omega-3 ( n -3) fatty acids (FAs) such as eicosapentaenoic and docosahexaenoic acid (EPA/DHA) from marine sources is known to have anti-inflammatory effects. However, molecular mechanisms underlying their beneficial effects on health are not fully understood. The aim of the present study was to characterize gene expression profiles of THP-1 macrophages, incubated in either EPA or DHA and stimulated with lipopolysaccharide (LPS), a pro-inflammatory agent. Methods: THP-1 macrophages were incubated into 10, 50 and 75 µM of EPA or DHA for 24 h, and 100 nM of LPS was added to the culture media for 18 h. Total mRNA was extracted and gene expression examined by microarray analysis using Illumina Human HT-12 expression beadchips (Illumina). Results: Pathway analysis revealed that EPA and DHA regulate genes involved in cell cycle regulation, apoptosis, immune response and inflammation, oxidative stress and cancer pathways in a differential and dose-dependent manner. Conclusions: EPA and DHA appear to exert differential effects on gene expression in THP-1 macrophages. Specific effects of n -3 FAs on gene expression levels are also dose-dependent.

  8. Oxidative modifications of conjugated and unconjugated linoleic acid during heating.

    Science.gov (United States)

    Giua, L; Blasi, F; Simonetti, M S; Cossignani, L

    2013-10-15

    The oxidative stability of conjugated linoleic (CLA) and linoleic (LA) acids in different chemical forms (free acids, methyl esters and homogeneous triacylglycerols) was compared. All model systems were heated at 180°C for different times (15, 30, 45 and 60min). The primary oxidation products were evaluated by spectrophometric analysis, while the volatile compounds were determined by solid phase micro-extraction (SPME), coupled with gas chromatography-mass spectrometry (HRGC-MS). The isomer profile modifications were investigated by silver-ion high performance liquid chromatography (Ag(+)-HPLC) equipped with an UV detector. Generally, peroxide values decreased during the heating time. Among the volatiles, saturated aldehydes were the most represented compounds. Isomerization of cis,trans and trans,cis CLA to trans,trans isomers was observed mainly for the methyl form of CLA. The three different chemical forms of LA never showed isomerization phenomena. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Dietary supplementation of finishing pigs with the docosahexaenoic acid-rich microalgae, Aurantiochytrium limacinum: effects on performance, carcass characteristics and tissue fatty acid profile.

    Science.gov (United States)

    Moran, Colm A; Morlacchini, Mauro; Keegan, Jason D; Fusconi, Giorgio

    2018-05-01

    The aim of this experiment was to evaluate the effect of dietary supplementation with the docosahexaenoic acid (DHA)-rich microalgae, Aurantiochytrium limacinum (AURA) on pig performance, carcass traits, and the fatty acid composition of pork Longissimus lumborum (LL) and backfat. A total of 144 Pig Improvement Company (PIC)×Goland finishing pigs (72 females and 72 castrated males) of mean weight 117.1 (±13.1) kg were blocked by sex and body weight and provided with 0% or 1% AURA in isonutritive and isocaloric diets. A total of 24 pens provided 12 replicates per treatment. Animals were weighed on day 0 and 28 with feed and water intake recorded per pen. After 31 days supplementation (28 days of study and 3 days until the slaughtering date) three animals per pen (n = 72) were slaughtered and the LL and backfat thickness, lean meat content and dressing percentage were recorded for the carcasses. The fatty acid (FA) profile of the LL and backfat was established by direct FA methyl ester synthesis. No differences were observed for any performance parameters or carcass traits. Supplementation with AURA resulted in significant changes to the FA profiles of both the LL and backfat with male and female pigs responding differently to supplementation in terms of particular FAs. Overall, pork LL samples had significantly higher eicosapentaenoic acid (p<0.001) and DHA concentrations (p<0.001), and higher omega-3 (n-3) FAs (p<0.001), as well as an increased omega3:omega6 (n-3:n-6) ratio (p = 0.001). For backfat, supplementation resulted in significantly higher amounts of DHA (p<0.001) and n-3 FAs (p<0.001). These results indicate that dietary supplementation with 1% AURA over a 31 day period can increase the FA composition of pork LL and backfat, specifically the DHA, with no major impact on growth performance and carcass traits.

  10. Benefits of Docosahexaenoic Acid, Folic Acid, Vitamin D and Iodine on Foetal and Infant Brain Development and Function Following Maternal Supplementation during Pregnancy and Lactation

    Directory of Open Access Journals (Sweden)

    Nancy L. Morse

    2012-07-01

    Full Text Available Scientific literature is increasingly reporting on dietary deficiencies in many populations of some nutrients critical for foetal and infant brain development and function. Purpose: To highlight the potential benefits of maternal supplementation with docosahexaenoic acid (DHA and other important complimentary nutrients, including vitamin D, folic acid and iodine during pregnancy and/or breast feeding for foetal and/or infant brain development and/or function. Methods: English language systematic reviews, meta-analyses, randomised controlled trials, cohort studies, cross-sectional and case-control studies were obtained through searches on MEDLINE and the Cochrane Register of Controlled Trials from January 2000 through to February 2012 and reference lists of retrieved articles. Reports were selected if they included benefits and harms of maternal supplementation of DHA, vitamin D, folic acid or iodine supplementation during pregnancy and/or lactation. Results: Maternal DHA intake during pregnancy and/or lactation can prolong high risk pregnancies, increase birth weight, head circumference and birth length, and can enhance visual acuity, hand and eye co-ordination, attention, problem solving and information processing. Vitamin D helps maintain pregnancy and promotes normal skeletal and brain development. Folic acid is necessary for normal foetal spine, brain and skull development. Iodine is essential for thyroid hormone production necessary for normal brain and nervous system development during gestation that impacts childhood function. Conclusion: Maternal supplementation within recommended safe intakes in populations with dietary deficiencies may prevent many brain and central nervous system malfunctions and even enhance brain development and function in their offspring.

  11. Conjugated Linoleic Acid Production by Bifidobacteria: Screening, Kinetic, and Composition

    Directory of Open Access Journals (Sweden)

    Stefano Raimondi

    2016-01-01

    Full Text Available Conjugated linoleic acids (CLA are positional and geometric isomers of linoleic acid involved in a number of health aspects. In humans, CLA production is performed by gut microbiota, including some species of potential probiotic bifidobacteria. 128 strains of 31 Bifidobacterium species were screened with a spectrophotometric assay to identify novel CLA producers. Most species were nonproducers, while producers belonged to B. breve and B. pseudocatenulatum. GC-MS revealed that CLA producer strains yielded 9cis,11trans-CLA and 9trans,11trans-CLA, without any production of other isomers. Hydroxylated forms of LA were absent in producer strains, suggesting that the myosin-cross-reactive antigen (MCRA protein that exerts hydratase activity is not involved in LA isomerization. Moreover, both CLA producer and nonproducer species bear a MCRA homologue. The strain B. breve WC 0421 was the best CLA producer, converting LA into 68.8% 9cis,11trans-CLA and 25.1% 9trans,11trans-CLA. Production occurred mostly during the lag and the exponential phase. For the first time, production and incorporation of CLA in biomass were assessed. B. breve WC 0421 stored CLA in the form of free fatty acids, without changing the composition of the esterified fatty acids, which mainly occurred in the plasmatic membrane.

  12. Whole-Body Docosahexaenoic Acid Synthesis-Secretion Rates in Rats Are Constant across a Large Range of Dietary α-Linolenic Acid Intakes.

    Science.gov (United States)

    Domenichiello, Anthony F; Kitson, Alex P; Metherel, Adam H; Chen, Chuck T; Hopperton, Kathryn E; Stavro, P Mark; Bazinet, Richard P

    2017-01-01

    Docosahexaenoic acid (DHA) is an ω-3 (n-3) polyunsaturated fatty acid (PUFA) thought to be important for brain function. Although the main dietary source of DHA is fish, DHA can also be synthesized from α-linolenic acid (ALA), which is derived from plants. Enzymes involved in DHA synthesis are also active toward ω-6 (n-6) PUFAs to synthesize docosapentaenoic acid n-6 (DPAn-6). It is unclear whether DHA synthesis from ALA is sufficient to maintain brain DHA. The objective of this study was to determine how different amounts of dietary ALA would affect whole-body DHA and DPAn-6 synthesis rates. Male Long-Evans rats were fed an ALA-deficient diet (ALA-D), an ALA-adequate (ALA-A) diet, or a high-ALA (ALA-H) diet for 8 wk from weaning. Dietary ALA concentrations were 0.07%, 3%, and 10% of the fatty acids, and ALA was the only dietary PUFA that differed between the diets. After 8 wk, steady-state stable isotope infusion of labeled ALA and linoleic acid (LA) was performed to determine the in vivo synthesis-secretion rates of DHA and DPAn-6. Rats fed the ALA-A diet had an ∼2-fold greater capacity to synthesize DHA than did rats fed the ALA-H and ALA-D diets, and a DHA synthesis rate that was similar to that of rats fed the ALA-H diet. However, rats fed the ALA-D diet had a 750% lower DHA synthesis rate than rats fed the ALA-A and ALA-H diets. Despite enrichment into arachidonic acid, we did not detect any labeled LA appearing as DPAn-6. Increasing dietary ALA from 3% to 10% of fatty acids did not increase DHA synthesis rates, because of a decreased capacity to synthesize DHA in rats fed the ALA-H diet. Tissue concentrations of DPAn-6 may be explained at least in part by longer plasma half-lives. © 2017 American Society for Nutrition.

  13. Developmental Outcomes at 24 Months of Age in Toddlers Supplemented with Arachidonic Acid and Docosahexaenoic Acid: Results of a Double Blind Randomized, Controlled Trial

    Directory of Open Access Journals (Sweden)

    Angela M. Devlin

    2017-09-01

    Full Text Available Little is known about arachidonic acid (ARA and docosahexaenoic acid (DHA requirements in toddlers. A longitudinal, double blind, controlled trial in toddlers (n = 133 age 13.4 ± 0.9 months (mean ± standard deviation, randomized to receive a DHA (200 mg/day and ARA (200 mg/day supplement (supplement or a corn oil supplement (control until age 24 months determined effects on neurodevelopment. We found no effect of the supplement on the Bayley Scales of Infant and Toddler Development 3rd Edition (Bayley-III cognitive and language composites and Beery–Buktenica Developmental Test of Visual–Motor Integration (Beery VMI at age 24 months. Supplemented toddlers had higher RBC phosphatidylcholine (PC, phosphatidylethanolamine (PE, and plasma DHA and ARA compared to placebo toddlers at age 24 months. A positive relationship between RBC PE ARA and Bayley III Cognitive composite (4.55 (0.21–9.00, B (95% CI, p = 0.045 in supplemented boys, but not in control boys, was observed in models adjusted for baseline fatty acid, maternal non-verbal intelligence, and BMI z-score at age 24 months. A similar positive relationship between RBC PE ARA and Bayley III Language composite was observed for supplemented boys (11.52 (5.10–17.94, p < 0.001 and girls (11.19 (4.69–17.68, p = 0.001. These findings suggest that increasing the ARA status in toddlers is associated with better neurodevelopment at age 24 months.

  14. The blood-brain barrier fatty acid transport protein 1 (FATP1/SLC27A1) supplies docosahexaenoic acid to the brain, and insulin facilitates transport.

    Science.gov (United States)

    Ochiai, Yusuke; Uchida, Yasuo; Ohtsuki, Sumio; Tachikawa, Masanori; Aizawa, Sanshiro; Terasaki, Tetsuya

    2017-05-01

    We purposed to clarify the contribution of fatty acid transport protein 1 (FATP1/SLC 27A1) to the supply of docosahexaenoic acid (DHA) to the brain across the blood-brain barrier in this study. Transport experiments showed that the uptake rate of [ 14 C]-DHA in human FATP1-expressing HEK293 cells was significantly greater than that in empty vector-transfected (mock) HEK293 cells. The steady-state intracellular DHA concentration was nearly 2-fold smaller in FATP1-expressing than in mock cells, suggesting that FATP1 works as not only an influx, but also an efflux transporter for DHA. [ 14 C]-DHA uptake by a human cerebral microvascular endothelial cell line (hCMEC/D3) increased in a time-dependent manner, and was inhibited by unlabeled DHA and a known FATP1 substrate, oleic acid. Knock-down of FATP1 in hCMEC/D3 cells with specific siRNA showed that FATP1-mediated uptake accounts for 59.2-73.0% of total [ 14 C]-DHA uptake by the cells. Insulin treatment for 30 min induced translocation of FATP1 protein to the plasma membrane in hCMEC/D3 cells and enhanced [ 14 C]-DHA uptake. Immunohistochemical analysis of mouse brain sections showed that FATP1 protein is preferentially localized at the basal membrane of brain microvessel endothelial cells. We found that two neuroprotective substances, taurine and biotin, in addition to DHA, undergo FATP1-mediated efflux. Overall, our results suggest that FATP1 localized at the basal membrane of brain microvessels contributes to the transport of DHA, taurine and biotin into the brain, and insulin rapidly increases DHA supply to the brain by promoting translocation of FATP1 to the membrane. Read the Editorial Comment for this article on page 324. © 2016 International Society for Neurochemistry.

  15. Developmental Outcomes at 24 Months of Age in Toddlers Supplemented with Arachidonic Acid and Docosahexaenoic Acid: Results of a Double Blind Randomized, Controlled Trial

    Science.gov (United States)

    Devlin, Angela M.; Chau, Cecil M. Y.; Matheson, Julie; McCarthy, Deanna; Yurko-Mauro, Karin; Innis, Sheila M.; Grunau, Ruth E.

    2017-01-01

    Little is known about arachidonic acid (ARA) and docosahexaenoic acid (DHA) requirements in toddlers. A longitudinal, double blind, controlled trial in toddlers (n = 133) age 13.4 ± 0.9 months (mean ± standard deviation), randomized to receive a DHA (200 mg/day) and ARA (200 mg/day) supplement (supplement) or a corn oil supplement (control) until age 24 months determined effects on neurodevelopment. We found no effect of the supplement on the Bayley Scales of Infant and Toddler Development 3rd Edition (Bayley-III) cognitive and language composites and Beery–Buktenica Developmental Test of Visual–Motor Integration (Beery VMI) at age 24 months. Supplemented toddlers had higher RBC phosphatidylcholine (PC), phosphatidylethanolamine (PE), and plasma DHA and ARA compared to placebo toddlers at age 24 months. A positive relationship between RBC PE ARA and Bayley III Cognitive composite (4.55 (0.21–9.00), B (95% CI), p = 0.045) in supplemented boys, but not in control boys, was observed in models adjusted for baseline fatty acid, maternal non-verbal intelligence, and BMI z-score at age 24 months. A similar positive relationship between RBC PE ARA and Bayley III Language composite was observed for supplemented boys (11.52 (5.10–17.94), p < 0.001) and girls (11.19 (4.69–17.68), p = 0.001). These findings suggest that increasing the ARA status in toddlers is associated with better neurodevelopment at age 24 months. PMID:28878181

  16. Retroconversion is a minor contributor to increases in eicosapentaenoic acid following docosahexaenoic acid feeding as determined by compound specific isotope analysis in rat liver.

    Science.gov (United States)

    Metherel, Adam H; Chouinard-Watkins, Raphaël; Trépanier, Marc-Olivier; Lacombe, R J Scott; Bazinet, Richard P

    2017-01-01

    Dietary docosahexaenoic acid (DHA, 22:6n-3) not only increases blood and tissue levels of DHA, but also eicosapentaenoic acid (EPA, 20:5n-3). It is generally believed that this increase is due to DHA retroconversion to EPA, however, a slower conversion of α-linolenic acid (ALA, 18:3n-3) derived EPA to downstream metabolic products (i.e. slower turnover of EPA) is equally plausible. In this study, 21-day old Long Evans rats were weaned onto an ALA only or DHA + ALA diet for 12 weeks. Afterwards, livers were collected and the natural abundance 13 C-enrichment was determined by compound specific isotope analysis (CSIA) of liver EPA by isotope ratio mass-spectrometry and compared to dietary ALA and DHA 13 C-enrichment. Isotopic signatures (per mil, ‰) for liver EPA were not different ( p  > 0.05) between the ALA only diet (-25.89 ± 0.39 ‰, mean ± SEM) and the DHA + ALA diet (-26.26 ± 0.40 ‰), suggesting the relative contribution from dietary ALA and DHA to liver EPA did not change. However, with DHA feeding estimates of absolute EPA contribution from ALA increased 4.4-fold (147 ± 22 to 788 ± 153 nmol/g) compared to 3.2-fold from DHA (91 ± 14 to 382 ± 13 nmol/g), respectively. In conclusion, CSIA of liver EPA in rats following 12-weeks of dietary DHA suggests that retroconversion of DHA to EPA is a relatively small contributor to increases in EPA, and that this increase in EPA is largely coming from elongation/desaturation of ALA.

  17. Whole-genome single-nucleotide polymorphism (SNP marker discovery and association analysis with the eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA content in Larimichthys crocea

    Directory of Open Access Journals (Sweden)

    Shijun Xiao

    2016-12-01

    Full Text Available Whole-genome single-nucleotide polymorphism (SNP markers are valuable genetic resources for the association and conservation studies. Genome-wide SNP development in many teleost species are still challenging because of the genome complexity and the cost of re-sequencing. Genotyping-By-Sequencing (GBS provided an efficient reduced representative method to squeeze cost for SNP detection; however, most of recent GBS applications were reported on plant organisms. In this work, we used an EcoRI-NlaIII based GBS protocol to teleost large yellow croaker, an important commercial fish in China and East-Asia, and reported the first whole-genome SNP development for the species. 69,845 high quality SNP markers that evenly distributed along genome were detected in at least 80% of 500 individuals. Nearly 95% randomly selected genotypes were successfully validated by Sequenom MassARRAY assay. The association studies with the muscle eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA content discovered 39 significant SNP markers, contributing as high up to ∼63% genetic variance that explained by all markers. Functional genes that involved in fat digestion and absorption pathway were identified, such as APOB, CRAT and OSBPL10. Notably, PPT2 Gene, previously identified in the association study of the plasma n-3 and n-6 polyunsaturated fatty acid level in human, was re-discovered in large yellow croaker. Our study verified that EcoRI-NlaIII based GBS could produce quality SNP markers in a cost-efficient manner in teleost genome. The developed SNP markers and the EPA and DHA associated SNP loci provided invaluable resources for the population structure, conservation genetics and genomic selection of large yellow croaker and other fish organisms.

  18. Mfsd2a Is a Transporter for the Essential ω-3 Fatty Acid Docosahexaenoic Acid (DHA) in Eye and Is Important for Photoreceptor Cell Development.

    Science.gov (United States)

    Wong, Bernice H; Chan, Jia Pei; Cazenave-Gassiot, Amaury; Poh, Rebecca W; Foo, Juat Chin; Galam, Dwight L A; Ghosh, Sujoy; Nguyen, Long N; Barathi, Veluchamy A; Yeo, Sia W; Luu, Chi D; Wenk, Markus R; Silver, David L

    2016-05-13

    Eye photoreceptor membrane discs in outer rod segments are highly enriched in the visual pigment rhodopsin and the ω-3 fatty acid docosahexaenoic acid (DHA). The eye acquires DHA from blood, but transporters for DHA uptake across the blood-retinal barrier or retinal pigment epithelium have not been identified. Mfsd2a is a newly described sodium-dependent lysophosphatidylcholine (LPC) symporter expressed at the blood-brain barrier that transports LPCs containing DHA and other long-chain fatty acids. LPC transport via Mfsd2a has been shown to be necessary for human brain growth. Here we demonstrate that Mfsd2a is highly expressed in retinal pigment epithelium in embryonic eye, before the development of photoreceptors, and is the primary site of Mfsd2a expression in the eye. Eyes from whole body Mfsd2a-deficient (KO) mice, but not endothelium-specific Mfsd2a-deficient mice, were DHA-deficient and had significantly reduced LPC/DHA transport in vivo Fluorescein angiography indicated normal blood-retinal barrier function. Histological and electron microscopic analysis indicated that Mfsd2a KO mice exhibited a specific reduction in outer rod segment length, disorganized outer rod segment discs, and mislocalization of and reduction in rhodopsin early in postnatal development without loss of photoreceptors. Minor photoreceptor cell loss occurred in adult Mfsd2a KO mice, but electroretinography indicated visual function was normal. The developing eyes of Mfsd2a KO mice had activated microglia and up-regulation of lipogenic and cholesterogenic genes, likely adaptations to loss of LPC transport. These findings identify LPC transport via Mfsd2a as an important pathway for DHA uptake in eye and for development of photoreceptor membrane discs. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. The Omega-3 Fatty Acid Docosahexaenoic Acid Modulates Inflammatory Mediator Release in Human Alveolar Cells Exposed to Bronchoalveolar Lavage Fluid of ARDS Patients

    Directory of Open Access Journals (Sweden)

    Paolo Cotogni

    2015-01-01

    Full Text Available Background. This study investigated whether the 1 : 2 ω-3/ω-6 ratio may reduce proinflammatory response in human alveolar cells (A549 exposed to an ex vivo inflammatory stimulus (bronchoalveolar lavage fluid (BALF of acute respiratory distress syndrome (ARDS patients. Methods. We exposed A549 cells to the BALF collected from 12 ARDS patients. After 18 hours, fatty acids (FA were added as docosahexaenoic acid (DHA, ω-3 and arachidonic acid (AA, ω-6 in two ratios (1 : 2 or 1 : 7. 24 hours later, in culture supernatants were evaluated cytokines (TNF-α, IL-6, IL-8, and IL-10 and prostaglandins (PGE2 and PGE3 release. The FA percentage content in A549 membrane phospholipids, content of COX-2, level of PPARγ, and NF-κB binding activity were determined. Results. The 1 : 2 DHA/AA ratio reversed the baseline predominance of ω-6 over ω-3 in the cell membranes (P < 0.001. The proinflammatory cytokine release was reduced by the 1 : 2 ratio (P < 0.01 to <0.001 but was increased by the 1 : 7 ratio (P < 0.01. The 1 : 2 ratio reduced COX-2 and PGE2 (P < 0.001 as well as NF-κB translocation into the nucleus (P < 0.01, while it increased activation of PPARγ and IL-10 release (P < 0.001. Conclusion. This study demonstrated that shifting the FA supply from ω-6 to ω-3 decreased proinflammatory mediator release in human alveolar cells exposed to BALF of ARDS patients.

  20. Effect of dietary conjugated linoleic acid (CLA) on the growth and ...

    African Journals Online (AJOL)

    p4208528

    Keywords: Conjugated linoleic acid, geese, growth, lipid metabolism, fatty acid composition .... For determination of serum total cholesterol (TC), LDL-C, high density ... separated and quantified by gas–liquid chromatography (Carlo Erba Vega ...

  1. Conjugated linoleic acid-rich soy oil triacylglycerol identification.

    Science.gov (United States)

    Lall, Rahul K; Proctor, Andrew; Jain, Vishal P; Lay, Jackson O

    2009-03-11

    Conjugated linoleic acid (CLA)-rich soy oil has been produced by soy oil linoleic acid (LA) photoisomerization, but CLA-rich oil triacylglycerol (TAG) characterization was not described. Therefore, the objectives were to identify and quantify new TAG fractions in CLA-rich oil by nonaqueous reversed-phase high-performance liquid chromatography (NARP-HPLC). Analytical NARP-HPLC with an acetonitrile/dichloromethane (ACN/DCM) gradient and an evaporating light scattering detector/ultraviolet (ELSD/UV) detector was used. New TAG peaks from LA-containing TAGs were observed. The LnLL, LLL, LLO, and LLP (Ln, linolenic; L, linoleic; O, oleic; and P, palmitic) peaks reduced after isomerization with an increase in adjacent peaks that coeluted with LnLnO, LnLO, LnOO, and LnPP. The newly formed peaks were wider than those of the original oil and absorbed at 233 nm, suggesting the possibility of various CLA containing TAGs. The HPLC profile showed five fractions of mixed TAGs, and fatty acid analysis showed that CLA isomers were found predominately in fractions 2 and 3, which originally contained most LA. The CLA isomers were 70-80% trans,trans and 20-30% cis,trans and trans,cis.

  2. Production of carrier-peptide conjugates using chemically reactive unnatural amino acids

    Science.gov (United States)

    Young, Travis; Schultz, Peter G

    2013-12-17

    Provided are methods of making carrier polypeptide that include incorporating a first unnatural amino acid into a carrier polypeptide variant, incorporating a second unnatural amino acid into a target polypeptide variant, and reacting the first and second unnatural amino acids to produce the conjugate. Conjugates produced using the provided methods are also provided. In addition, orthogonal translation systems in methylotrophic yeast and methods of using these systems to produce carrier and target polypeptide variants comprising unnatural amino acids are provided.

  3. Arachidonic acid-and docosahexaenoic acid-enriched formulas modulate antigen-specific T cell responses to influenza virus in neonatal piglets.

    Science.gov (United States)

    Bassaganya-Riera, Josep; Guri, Amir J; Noble, Alexis M; Reynolds, Kathryn A; King, Jennifer; Wood, Cynthia M; Ashby, Michael; Rai, Deshanie; Hontecillas, Raquel

    2007-03-01

    Whereas the immunomodulatory effects of feeding either arachidonic acid (AA) or docosahexaenoic acid (DHA) separately have been previously investigated, little is known about the immunomodulatory efficacy of AA or DHA when they are fed in combination as infant formula ingredients. The objective of this study was to investigate the ability of AA- and DHA(AA/DHA)-enriched infant formula to modulate immune responses in the neonate in response to an inactivated influenza virus vaccine. Neonatal piglets (n = 48) were weaned on day 2 of age and distributed into 16 blocks of 3 littermate piglets each. Within each block, piglets were randomly assigned to a control formula, AA/DHA-enriched formula (0.63% AA and 0.34% DHA), or sow milk for 30 d. On day 9, 8 blocks of piglets were immunized with an inactivated influenza virus vaccine. On days 0, 9, 16, 23, and 30 after weaning, we measured influenza virus-specific T cell proliferation and phenotype of T subsets in peripheral blood. A delayed-type hypersensitivity reaction test was administered on day 28. Cytokine messenger RNA expression was determined by quantitative real time reverse transcriptase-polymerase chain reaction on day 30. The influenza virus-specific CD4(+) and CD8(+) T cell ex vivo lymphoproliferative responses were significantly lower on day 23 after immunization in piglets receiving dietary AA/DHA supplementation and sow milk than in those receiving the unsupplemented control formula. The immunomodulatory effects of AA/DHA-enriched formulas were consistent with up-regulation of interleukin 10 in peripheral blood mononuclear cells. Overall, it appears that the AA/DHA-enriched formula modulated antigen-specific T cell responses in part through an interleukin 10-dependent mechanism.

  4. Omega-3 fatty acid docosahexaenoic acid increases SorLA/LR11, a sorting protein with reduced expression in sporadic Alzheimer's disease (AD): relevance to AD prevention.

    Science.gov (United States)

    Ma, Qiu-Lan; Teter, Bruce; Ubeda, Oliver J; Morihara, Takashi; Dhoot, Dilsher; Nyby, Michael D; Tuck, Michael L; Frautschy, Sally A; Cole, Greg M

    2007-12-26

    Environmental and genetic factors, notably ApoE4, contribute to the etiology of late-onset Alzheimer's disease (LOAD). Reduced mRNA and protein for an apolipoprotein E (ApoE) receptor family member, SorLA (LR11) has been found in LOAD but not early-onset AD, suggesting that LR11 loss is not secondary to pathology. LR11 is a neuronal sorting protein that reduces amyloid precursor protein (APP) trafficking to secretases that generate beta-amyloid (Abeta). Genetic polymorphisms that reduce LR11 expression are associated with increased AD risk. However these polymorphisms account for only a fraction of cases with LR11 deficits, suggesting involvement of environmental factors. Because lipoprotein receptors are typically lipid-regulated, we postulated that LR11 is regulated by docosahexaenoic acid (DHA), an essential omega-3 fatty acid related to reduced AD risk and reduced Abeta accumulation. In this study, we report that DHA significantly increases LR11 in multiple systems, including primary rat neurons, aged non-Tg mice and an aged DHA-depleted APPsw AD mouse model. DHA also increased LR11 in a human neuronal line. In vivo elevation of LR11 was also observed with dietary fish oil in young rats with insulin resistance, a model for type II diabetes, another AD risk factor. These data argue that DHA induction of LR11 does not require DHA-depleting diets and is not age dependent. Because reduced LR11 is known to increase Abeta production and may be a significant genetic cause of LOAD, our results indicate that DHA increases in SorLA/LR11 levels may play an important role in preventing LOAD.

  5. Eicosapentaenoic acid (EPA) vs. Docosahexaenoic acid (DHA): Effects in epididymal white adipose tissue of mice fed a high-fructose diet.

    Science.gov (United States)

    Bargut, Thereza Cristina Lonzetti; Santos, Larissa Pereira; Machado, Daiana Guimarães Lopes; Aguila, Marcia Barbosa; Mandarim-de-Lacerda, Carlos Alberto

    2017-08-01

    Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been demonstrated to be beneficial for many diseases, including those associated with the metabolic syndrome (e.g. insulin resistance and hypertension). Nevertheless, not only their actions are not entirely understood, but also their only effects were not yet elucidated. Therefore, we aimed to compare the effects of EPA and DHA, alone or in combination, on the epididymal white adipose tissue (WAT) metabolism in mice fed a high-fructose diet. 3-mo-old C57Bl/6 mice were fed a control diet (C) or a high-fructose diet (HFru). After three weeks on the diets, the HFru group was subdivided into four new groups for another five weeks: HFru, HFru+EPA, HFru+DHA, and HFru-EPA+DHA (n=10/group). Besides evaluating biometric and metabolic parameters of the animals, we measured the adipocyte area and performed molecular analyses (inflammation and lipolysis) in the epididymal WAT. The HFru group showed adipocyte hypertrophy, inflammation, and uncontrolled lipolysis. The treated animals showed a reversion of adipocyte hypertrophy, inhibition of inflammation with activation of anti-inflammatory mediators, and regularization of lipolysis. Overall, the beneficial effects were more marked with DHA than EPA. Although the whole-body metabolic effects were similar between EPA and DHA, DHA appeared to be the central actor in WAT metabolism, modulating pro and anti-inflammatory pathways and alleviating adipocytes abnormalities. Therefore, when considering fructose-induced adverse effects in WAT, the most prominent actions were observed with DHA. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Synthesis and biological activity of amino acid conjugates of abscisic acid.

    Science.gov (United States)

    Todoroki, Yasushi; Narita, Kenta; Muramatsu, Taku; Shimomura, Hajime; Ohnishi, Toshiyuki; Mizutani, Masaharu; Ueno, Kotomi; Hirai, Nobuhiro

    2011-03-01

    We prepared 19 amino acid conjugates of the plant hormone abscisic acid (ABA) and investigated their biological activity, enzymatic hydrolysis by a recombinant Arabidopsis amidohydrolases GST-ILR1 and GST-IAR3, and metabolic fate in rice seedlings. Different sets of ABA-amino acids induced ABA-like responses in different plants. Some ABA-amino acids, including some that were active in bioassays, were hydrolyzed by recombinant Arabidopsis GST-IAR3, although GST-ILR1 did not show hydrolysis activity for any of the ABA-amino acids. ABA-L-Ala, which was active in all the bioassays, an Arabidopsis seed germination, spinach seed germination, and rice seedling elongation assays, except in a lettuce seed germination assay and was hydrolyzed by GST-IAR3, was hydrolyzed to free ABA in rice seedlings. These findings suggest that some plant amidohydrolases hydrolyze some ABA-amino acid conjugates. Because our study indicates the possibility that different plants have hydrolyzing activity toward different ABA-amino acids, an ABA-amino acid may function as a species-selective pro-hormone of ABA. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Production of conjugated linoleic acid-rich potato chips.

    Science.gov (United States)

    Jain, Vishal P; Proctor, Andrew

    2007-01-01

    Conjugated linoleic acid (CLA) is found primarily in diary and beef products, but the health benefits of CLA can only be realized if they are consumed at much greater levels than a normal healthy dietary intake. We have recently shown that a CLA-rich soy oil can be produced by simple isomerization of linoleic acid in soy oil by photoirradiation. This oil may allow greatly increased dietary CLA without significantly elevating fat intake. The objective of this study was to prepare CLA-rich potato chips by frying in CLA-rich soy oil. Soy oil was photoisomerized in the presence of iodine catalyst with UV/visible light. The irradiated oil was clay processed to remove the residual iodine and this oil was then used to fry potato chips. Oil was extracted from fried chips and analyzed for its CLA content with gas chromatography. A 1-oz serving of CLA-rich potato chips contained approximately 2.4 g CLA as compared to 0.1 g CLA in 3-oz serving of steak fillet and 0.06 g CLA in 8-oz serving of whole milk. The peroxide value of the oil extracted from potato chips was found to be 1 meq/1000 g sample, which was within the acceptable commercial standards. This study may lead to the commercialization of CLA-rich food products.

  8. Blood fatty acid composition of pregnant and nonpregnant Korean women: red cells may act as a reservoir of arachidonic acid and docosahexaenoic acid for utilization by the developing fetus.

    Science.gov (United States)

    Ghebremeskel, K; Min, Y; Crawford, M A; Nam, J H; Kim, A; Koo, J N; Suzuki, H

    2000-05-01

    Relative fatty acid composition of plasma and red blood cell (RBC) choline phosphoglycerides (CPG), and RBC ethanolamine phosphoglycerides (EPG) of pregnant (n = 40) and nonpregnant, nonlactating (n = 40), healthy Korean women was compared. The two groups were of the same ethnic origin and comparable in age and parity. Levels of arachidonic (AA) and docosahexaenoic (DHA) acids were lower (P mothers were mobilizing membrane AA and DHA to meet the high fetal requirement for these nutrients. It may also suggest that RBC play a role as a potential store of AA and DHA and as a vehicle for the transport of these fatty acids from maternal circulation to the placenta to be utilized by the developing fetus.

  9. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion related to the Tolerable Upper Intake Level of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA)

    DEFF Research Database (Denmark)

    Tetens, Inge

    Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to deliver a scientific opinion on the Tolerable Upper Intake Level (UL) of the n-3 LCPUFAs eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA......). Available data are insufficient to establish a UL for n-3 LCPUFA (individually or combined) for any population group. At observed intake levels, consumption of n-3 LCPUFA has not been associated with adverse effects in healthy children or adults. Long-term supplemental intakes of EPA and DHA combined up...... to about 5 g/day do not appear to increase the risk of spontaneous bleeding episodes or bleeding complications, or affect glucose homeostasis immune function or lipid peroxidation, provided the oxidative stability of the n-3 LCPUFAs is guaranteed. Supplemental intakes of EPA and DHA combined at doses of 2...

  10. Eicosapentaenoic Acid and Docosahexaenoic Acid in Whole Blood Are Differentially and Sex-Specifically Associated with Cardiometabolic Risk Markers in 8–11-Year-Old Danish Children

    Science.gov (United States)

    Damsgaard, Camilla T.; Eidner, Maj B.; Stark, Ken D.; Hjorth, Mads F.; Sjödin, Anders; Andersen, Malene R.; Andersen, Rikke; Tetens, Inge; Astrup, Arne; Michaelsen, Kim F.; Lauritzen, Lotte

    2014-01-01

    n-3 long-chain polyunsaturated fatty acids improve cardiovascular risk markers in adults. These effects may differ between eicosapentaenoic acid (EPA, 20∶5n-3) and docosahexaenoic acid (DHA, 22∶6n-3), but we lack evidence in children. Using baseline data from the OPUS School Meal Study we 1) investigated associations between EPA and DHA in whole blood and early cardiometabolic risk markers in 713 children aged 8–11 years and 2) explored potential mediation through waist circumference and physical activity and potential dietary confounding. We collected data on parental education, pubertal stage, 7-day dietary records, physical activity by accelerometry and measured anthropometry, blood pressure, and heart rate. Blood samples were analyzed for whole blood fatty acid composition, cholesterols, triacylglycerol, insulin resistance by the homeostatic model of assessment (HOMA-IR), and inflammatory markers. Whole blood EPA was associated with a 2.7 mmHg (95% CI 0.4; 5.1) higher diastolic blood pressure per weight% EPA, but only in boys. Heart rate was negatively associated with both EPA and DHA status (P = 0.02 and P = 0.002, respectively). Whole blood EPA was negatively associated with triacylglycerol (P = 0.003) and positively with total cholesterol, low density and high density lipoprotein (HDL) cholesterol and HDL:triacylglycerol (all P<0.01) whereas DHA was negatively associated with insulin and HOMA-IR (P = 0.003) and tended to be negatively associated with a metabolic syndrome-score (P = 0.05). Adjustment for waist circumference and physical activity did not change the associations. The association between DHA and HOMA-IR was attenuated but remained after adjustment for fiber intake and none of the other associations were confounded by dietary fat, protein, fiber or energy intake. This study showed that EPA status was negatively associated with triacylglycerol and positively with cholesterols whereas DHA was negatively associated with

  11. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and gamma-linolenic acid (GLA) and contribution to normal cognitive function (ID 532) and maintenance

    DEFF Research Database (Denmark)

    Tetens, Inge

    claims in relation to docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and gamma-linolenic acid (GLA) and contribution to normal cognitive function and maintenance of normal bone. The scientific substantiation is based on the information provided by the Member States in the consolidated list...... and fish oil”. From the references provided, the Panel assumes that the food constituents that are the subject of the claims are the n-6 fatty acid gamma-linolenic acid (GLA) in evening primrose oil and the n-3 long-chain polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA...... of Article 13 health claims and references that EFSA has received from Member States or directly from stakeholders. The food constituents that are the subjects of the health claims are “omega-3 and omega-6 fatty acids (GLA)”, “gamma-linolenic acid + eicosapentaenoic acid (GLA+EPA)”, and “evening primrose oil...

  12. Mefenamic acid conjugates based on a hydrophilic biopolymer hydroxypropylcellulose: novel prodrug design, characterization and thermal analysis

    International Nuclear Information System (INIS)

    Hussain, M.A.; Kausar, R.; Amin, M.

    2015-01-01

    Macromolecular prodrugs (MPDs) of mefenamic acid were designed onto a cellulose ether derivative hydroxypropylcellulose (HPC) as ester conjugates. Fabrication of HPC-mefenamic acid conjugates was achieved by using p-toluenesulfonyl chloride as carboxylic acid (a functional group in drug) activator at 80 degree C for 24 h under nitrogen atmosphere. Reaction was preceded under homogeneous reaction conditions as HPC was dissolved before use in DMAc solvent. Imidazole was used as a base. Easy workup reactions resulted in good yields (55-65%) and degree of substitution (DS) of drug (0.37-0.99) onto HPC. The DS was calculated by acid-base titration after saponification and UV/Vis spectrophotometry after hydrolysis. DS by both of the methods was found in good agreement with each other. Aqueous and organic soluble novel prodrugs of mefenamic acid were purified and characterized by different spectroscopic and thermal analysis techniques. The initial, maximum and final degradation temperatures of HPC, mefenamic acid and HPC-mefenamic acid conjugates were drawn from thermogravimetric (TG) and derivative TG curves and compared to access relative thermal stability. The TG analysis has indicated that samples obtained were thermally more stable especially with increased stability of mefenamic acid in HPC-mefenamic acid conjugates. These novel MPDs of mefenamic acid (i.e., HPC-mefenamic acid conjugates) may have potential applications in pharmaceutically viable drug design due to wide range of solubility and extra thermal stability imparted after MPD formation. (author)

  13. Docosahexaenoic acid (DHA) at the sn-2 position of triacylglycerols increases DHA incorporation in brown, but not in white adipose tissue, of hamsters.

    Science.gov (United States)

    Lopes, Paula A; Bandarra, Narcisa M; Martins, Susana V; Madeira, Marta S; Ferreira, Júlia; Guil-Guerrero, José L; Prates, José A M

    2018-06-01

    We hypothesised that the incorporation of docosahexaenoic acid (DHA) across adipose tissues will be higher when it is ingested as triacylglycerols (TAG) structured at the sn-2 position. Ten-week old male hamsters were allocated to 4 dietary treatments (n = 10): linseed oil (LSO-control group), fish oil (FO), fish oil ethyl esters (FO-EE) and structured DHA at the sn-2 position of TAG (DHA-SL) during 12 weeks. In opposition to the large variations found for fatty acid composition in retroperitoneal white adipose tissue (WAT), brown adipose tissue (BAT) was less responsive to diets. DHA was not found in subcutaneous and retroperitoneal WAT depots but it was successfully incorporated in BAT reaching the highest percentage in DHA-SL. The PCA on plasma hormones (insulin, leptin, adiponectin) and fatty acids discriminated BAT from WATs pointing towards an individual signature on fatty acid deposition, but did not allow for full discrimination of dietary treatments within each adipose tissue.

  14. Production of a conjugated fatty acid by Bifidobacterium breve LMC520 from α-linolenic acid: conjugated linolenic acid (CLnA).

    Science.gov (United States)

    Park, Hui Gyu; Cho, Hyung Taek; Song, Myoung-Chong; Kim, Sang Bum; Kwon, Eung Gi; Choi, Nag Jin; Kim, Young Jun

    2012-03-28

    This study was performed to characterize natural CLnA isomer production by Bifidobacterium breve LMC520 of human origin in comparison to conjugated linoleic acid (CLA) production. B. breve LMC520 was found to be highly active in terms of CLnA production, of which the major portion was identified as cis-9,trans-11,cis-15 CLnA isomer by GC-MS and NMR analysis. B. breve LMC520 was incubated for 48 h using MRS medium (containing 0.05% L-cysteine · HCl) under different environmental conditions such as atmosphere, pH, and substrate concentration. The high conversion rate of α-linolenic acid (α-LNA) to CLnA (99%) was retained up to 2 mM α-LNA, and the production was proportionally increased nearly 7-fold with 8 mM by the 6 h of incubation under anaerobic conditions at a wide range of pH values (between 5 and 9). When α-LNA was compared with linoleic acid (LA) as a substrate for isomerization by B. breve LMC520, the conversion of α-LNA was higher than that of LA. These results demonstrated that specific CLnA isomer could be produced through active bacterial conversion at an optimized condition. Because many conjugated octadecatrienoic acids in nature are shown to play many positive roles, the noble isomer found in this study has potential as a functional source.

  15. The influence of feeding linoleic, gamma-linolenic and docosahexaenoic acid rich oils on rat brain tumor fatty acids composition and fatty acid binding protein 7 mRNA expression

    Directory of Open Access Journals (Sweden)

    Abdi Khosro

    2008-11-01

    Full Text Available Abstract Background Experimental studies indicate that gamma linolenic acid (GLA and docosahexaenoic acid (DHA may inhibit glioma cells growth but effects of oral consumption of these fatty acids on brain tumor fatty acid composition have not been determined in vivo. Methods GLA oil (GLAO; 72% GLA, DHA oil (DHAO; 73% DHA were fed to adult wistar rats (1 mL/rat/day starting one week prior to C6 glioma cells implantation and continued for two weeks after implantation. Control group were fed same amount of high linoleic acid safflower oil (74–77% linoleic acid. Fatty acid composition of tumor samples was determined in a set of 8–12 animals in each group and serum fatty acid in 6 animals per each group. Gene expression of tumor fatty acid binding protein 7 (FABP7, epidermal growth factor receptor (EGFR, peroxisome proliferator activated receptor γ (PPAR-γ and retinoid × receptor-α (RXR-α were determined in a set of 18 animals per group. Results DHAO feeding increased EPA of brain tumors and decreased ratio of n-6/n-3 fatty acids. Serum levels of EPA were also increased in DHAO group. A similar trend in serum and tumor levels of DHA were observed in DHAO group but it did not achieve statistical significance. GLAO increased serum concentration of GLA but had no significant effect on tumor GLA or dihomo-gamma linolenic acid (DGLA concentrations. Gene expression of FABP7 was up-regulated in tumors of DHAO group but no other significant effects were observed on EGFR, PPAR-γ or RXR-α expression, and expression of these genes in tumors of GLAO were not different from SFO group. Conclusion Dietary supplementation of DHA containing oil could be an effective way to increase levels of long chain n-3 fatty acids in brain tumors and this increase may be mediated partly by up-regulation of FABP7 expression.

  16. The hydroxylated form of docosahexaenoic acid (DHA-H) modifies the brain lipid composition in a model of Alzheimer's disease, improving behavioral motor function and survival.

    Science.gov (United States)

    Mohaibes, Raheem J; Fiol-deRoque, María A; Torres, Manuel; Ordinas, Margarita; López, David J; Castro, José A; Escribá, Pablo V; Busquets, Xavier

    2017-09-01

    We have compared the effect of the commonly used ω-3 fatty acid, docosahexaenoic acid ethyl ester (DHA-EE), and of its 2-hydroxylated DHA form (DHA-H), on brain lipid composition, behavior and lifespan in a new human transgenic Drosophila melanogaster model of Alzheimer's disease (AD). The transgenic flies expressed human Aβ42 and tau, and the overexpression of these human transgenes in the CNS of these flies produced progressive defects in motor function (antigeotaxic behavior) while reducing the animal's lifespan. Here, we demonstrate that both DHA-EE and DHA-H increase the longer chain fatty acids (≥18C) species in the heads of the flies, although only DHA-H produced an unknown chromatographic peak that corresponded to a non-hydroxylated lipid. In addition, only treatment with DHA-H prevented the abnormal climbing behavior and enhanced the lifespan of these transgenic flies. These benefits of DHA-H were confirmed in the well characterized transgenic PS1/APP mouse model of familial AD (5xFAD mice), mice that develop defects in spatial learning and in memory, as well as behavioral deficits. Hence, it appears that the modulation of brain lipid composition by DHA-H could have remedial effects on AD associated neurodegeneration. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá. Copyright © 2017. Published by Elsevier B.V.

  17. Comparison of linoleic and conjugated linoleic acids in enzymatic acidolysis of tristearin

    DEFF Research Database (Denmark)

    Yang, Tiankui; Xu, Xuebing; Li, L.T.

    2001-01-01

    tristearin (SSS) and linoleic (L) or conjugated linoleic (cL) acids (1:6, mol/mol). The other was between tristearin and the mixture of linoleic and conjugated linoleic acids (1:3:3, mol/mol/mol). Acyl incorporation and migration together with triacylglycerol composition of the products were monitored...... with gas chromatography, pancreatic lipase hydrolysis, and high performance liquid chromatography. Both acyl incorporation and migration of linoleic acid were faster than those of conjugated linoleic acid. At 5 h reaction, there were 13.0% LLL, 46.5% LSL, 27.7% LSS, and 5.6% SSS in the product for a system...... between tristearin and linoleic acid; whereas there were 2.4% cLcLcL, 10.4% cLScL, 50.9% cLSS, and 36.2% SSS in the product for a system between tristearin and conjugated linoleic acid. The results suggest that linoleic acid was more reactive than conjugated linoleic acid in the enzymatic acidolysis...

  18. Conjugated linolenic acids (CLnA, super CLA – natural sources and biological activity

    Directory of Open Access Journals (Sweden)

    Agnieszka Białek

    2014-11-01

    Full Text Available Polyunsaturated fatty acids (PUFA have a wide range of biological activity. Among them conjugated fatty acids are of great interest. Conjugated linoleic acids (CLA, which exert a multidirectional health-benefiting influence, and conjugated linolenic acids (CLnA, super CLA are examples of this group of fatty acids. CLnA are a group of positional and geometric isomers of octadecatrienoic acid (C18:3, which possess double bonds at positions 9, 11, 13 or 8, 10, 12 of their chain. Some vegetable oils are rich sources of CLnA, e.g. bitter melon oil (from Momordica charantia seeds and pomegranate oil (from Punica granatum seeds. The aim of this paper was to present information concerning natural sources and health-promoting activities of conjugated linolenic acids.The presented data reveal that conjugated linolenic acids may be very useful in prevention and treatment of many diseases, especially diabetes, arteriosclerosis , obesity and cancers (mammary, prostate and colon cancer. Among many potential mechanisms of their action, the fact that some CLnA are converted by oxidoreductases into CLA is very important. It seems to be very reasonable to conduct research concerning the possibility of CLnA use in prevention of many diseases.

  19. Ibuprofen-conjugated hyaluronate/polygalacturonic acid hydrogel for the prevention of epidural fibrosis.

    Science.gov (United States)

    Lin, Cheng-Yi; Peng, Hsiu-Hui; Chen, Mei-Hsiu; Sun, Jui-Sheng; Chang, Chih-Ju; Liu, Tse-Ying; Chen, Ming-Hong

    2016-05-01

    The formation of fibrous tissue is part of the natural healing response following a laminectomy. Severe scar tissue adhesion, known as epidural fibrosis, is a common cause of failed back surgery syndrome. In this study, by combining the advantages of drug treatment with a physical barrier, an ibuprofen-conjugated crosslinkable polygalacturonic acid and hyaluronic acid hydrogel was developed for epidural fibrosis prevention. Conjugation was confirmed and measured by 1D(1)H NMR spectroscopy.In vitroanalysis showed that the ibuprofen-conjugated polygalacturonic acid-hyaluronic acid hydrogel showed low cytotoxicity. In addition, the conjugated ibuprofen decreased prostaglandin E2production of the lipopolysaccharide-induced RAW264.7 cells. Histological data inin vivostudies indicated that the scar tissue adhesion of laminectomized male adult rats was reduced by the application of our ibuprofen-conjugated polygalacturonic acid-hyaluronic acid hydrogel. Its use also reduced the population of giant cells and collagen deposition of scar tissue without inducing extensive cell recruitment. The results of this study therefore suggest that the local delivery of ibuprofenviaa polygalacturonic acid-hyaluronic acid-based hydrogel reduces the possibility of epidural fibrosis. © The Author(s) 2016.

  20. Functionalization of Fatty Acid Vesicles through Newly Synthesized Bolaamphiphile-DNA Conjugates

    DEFF Research Database (Denmark)

    Wamberg, M. C.; Wieczorek, R.; Brier, S. B.

    2014-01-01

    The surface functionalization of fatty acid vesicles will allow their use as nanoreactors for complex chemistry. In this report, the tethering of several DNA conjugates to decanoic acid vesicles for molecular recognition and synthetic purposes was explored. Due to the highly dynamic nature......), and consists of a single hydrocarbon chain of 20 carbons having on one end a triazole group linked to the S'-phosphate of the nucleic acid and on the other side a hydroxyl-group. Its insertion was so effective that a fluorescent label on the DNA complementary to the conjugate could be used to visualize fatty...... acid structures....

  1. Fatty acid profiles in tissues of mice fed conjugated linoleic acid

    DEFF Research Database (Denmark)

    Gøttsche, Jesper; Straarup, Ellen Marie

    2006-01-01

    The incorporation of vaccenic acid (VA, 0.5 and 1.2%), conjugated linoleic acid (CLA, mixture of primarily c9,t11- and t10,c12-CLA, 1.2%), linoleic acid (LA, 1.2%) and oleic acid (OA, 1.2%) into different tissues of mice was examined. The effects on the fatty acid composition of triacylglycerols...... (TAG) and phospholipids (PL) in kidney, spleen, liver and adipose tissue were investigated. VA and CLA (c9,t11- and t10,c12-CLA) were primarily found in TAG, especially in kidney and adipose tissue, respectively. Conversion of VA to c9,t11-CLA was indicated by our results, as both fatty acids were...... incorporated into all the analyzed tissues when a diet containing VA but not c9,t11-CLA was fed. Most of the observed effects on the fatty acid profiles were seen in the CLA group, whereas only minor effects were observed in the VA groups compared with the CA group. Thus, CLA increased n-3 polyunsaturated...

  2. Circulating Docosahexaenoic Acid Associates with Insulin-Dependent Skeletal Muscle and Whole Body Glucose Uptake in Older Women Born from Normal Weight Mothers

    Directory of Open Access Journals (Sweden)

    Robert M. Badeau

    2017-02-01

    Full Text Available Background: Obesity among pregnant women is common, and their offspring are predisposed to obesity, insulin resistance, and diabetes. The circulating metabolites that are related to insulin resistance and are associated with this decreased tissue-specific uptake are unknown. Here, we assessed metabolite profiles in elderly women who were either female offspring from obese mothers (OOM or offspring of lean mothers (OLM. Metabolic changes were tested for associations with metrics for insulin resistance. Methods: Thirty-seven elderly women were separated into elderly offspring from obese mothers (OOM; n = 17 and elderly offspring from lean/normal weight mothers (OLM; n = 20 groups. We measured plasma metabolites using proton nuclear magnetic resonance (1H-NMR and insulin-dependent tissue-specific glucose uptake in skeletal muscle was assessed. Associations were made between metabolites and glucose uptake. Results: Compared to the OLM group, we found that the docosahexaenoic acid percentage of the total long-chain n-3 fatty acids (DHA/FA was significantly lower in OOM (p = 0.015. DHA/FA associated significantly with skeletal muscle glucose uptake (GU (p = 0.031 and the metabolizable glucose value derived from hyperinsulinemic-euglycemic clamp technique (M-value in the OLM group only (p = 0.050. Conclusions: DHA/FA is associated with insulin-dependent skeletal muscle glucose uptake and this association is significantly weakened in the offspring of obese mothers.

  3. The intramolecular position of docosahexaenoic acid in the triacylglycerol sources used for pediatric nutrition has a minimal effect on its metabolic use.

    Science.gov (United States)

    Sala-Vila, Aleix; Castellote, Ana I; López-Sabater, M Carmen

    2008-03-01

    Docosahexaenoic acid (DHA) plays an important role in normal development of the brain and retina in the human. In utero, DHA is incorporated in the fetus, and its accretion continues throughout early postnatal life. Although human breast milk contains this fatty acid, several organizations recommend supplementing infant formulas with DHA for infants and premature infants. Traditionally, certain types of fish oil have been used for fortifying some infant formulas, but with the decline in world fisheries, the search for alternative sources of DHA continues. Among the viable ingredient sources of DHA is oil derived from single-cell organisms (marine microorganisms); however, these oil sources display different positional specificity of DHA in the glycerol lipids compared with that found in human breast milk lipids. In the latter, the DHA is mainly esterified in the central position of the glycerol backbone. Because of these differences in human milk and oils derived from single-cell organisms, recent research in biotechnology has focused on developing new structured triacylglycerols with an intramolecular structure resembling that found in human milk lipids. This research is justified by the potential differences in metabolism of DHA based on the hypothetical bioavailability and benefits in DHA found in human milk lipids. Presented herein is a review of the published research on the metabolism of DHA from different triacylglycerol sources including in vitro studies and animal studies. Despite small differences observed in digestion, the current data reveal a minimal effect on the parameters of development studied for the intramolecular position in which DHA is esterified.

  4. Docosahexaenoic acid for reading, working memory and behavior in UK children aged 7-9: A randomized controlled trial for replication (the DOLAB II study).

    Science.gov (United States)

    Montgomery, Paul; Spreckelsen, Thees F; Burton, Alice; Burton, Jennifer R; Richardson, Alexandra J

    2018-01-01

    Omega-3 fatty acids are central to brain-development of children. Evidence from clinical trials and systematic reviews demonstrates the potential of long-chain Omega-3 supplementation for learning and behavior. However, findings are inconclusive and in need of robust replication studies since such work is lacking. Replication of the 2012 DOLAB 1 study findings that a dietary supplementation with the long-chain omega-3 docosahexaenoic acid (DHA) had beneficial effects on the reading, working memory, and behavior of healthy schoolchildren. Parallel group, fixed-dose, randomized (minimization, 30% random element), double-blind, placebo-controlled trial (RCT). Mainstream primary schools (n = 84) from five counties in the UK in 2012-2015. Healthy children aged 7-9 underperforming in reading (reading, working memory, and behavior, parent-rated and as secondary outcome teacher-rated. 376 children were randomized. Reading, working memory, and behavior change scores showed no consistent differences between intervention and placebo group. Some behavioral subscales showed minor group differences. This RCT did not replicate results of the earlier DOLAB 1 study on the effectiveness of nutritional supplementation with DHA for learning and behavior. Possible reasons are discussed, particularly regarding the replication of complex interventions. www.controlled-trials.com (ISRCTN48803273) and protocols.io (https://dx.doi.org/10.17504/protocols.io.k8kczuw).

  5. Evidence for the essentiality of arachidonic and docosahexaenoic acid in the postnatal maternal and infant diet for the development of the infant's immune system early in life.

    Science.gov (United States)

    Richard, Caroline; Lewis, Erin D; Field, Catherine J

    2016-05-01

    Long-chain polyunsaturated fatty acids (LCPUFA), especially the balance between arachidonic (AA) and docosahexaenoic (DHA) acids are known to have important immunomodulatory roles during the postnatal period when the immune system is rapidly developing. AA and DHA are required in infant formula in many countries but are optional in North America. The rationale for adding these LCPUFA to full-term formula is based on their presence in breast milk and randomized controlled studies that suggest improved cognitive function in preterm infants, but results are more variable in full-term infants. Recently, the European Food Safety Authority has proposed, based on a lack of functional evidence, that AA is not required in infant formula for full-term infants during the first year of life but DHA should remain mandatory. The purpose of this review is to review the evidence from epidemiological and intervention studies regarding the essentiality of AA and DHA in the postnatal infant and maternal diet (breast-feeding) for the immune system development early in life. Although studies support the essentiality of DHA for the immune system development, more research is needed to rule out the essentiality of AA. Nevertheless, intervention studies have demonstrated improvement in many markers of immune function in infants fed formula supplemented with AA and DHA compared with unsupplemented formula, which appears to consistently result in beneficial health outcomes including reduction in the risk of developing allergic and atopic disease early in life.

  6. The validation & verification of an LC/MS method for the determination of total docosahexaenoic acid concentrations in canine blood serum.

    Science.gov (United States)

    Dillon, Gerald Patrick; Keegan, Jason D; Wallace, Geoff; Yiannikouris, Alexandros; Moran, Colm Anthony

    2018-06-01

    Docosahexaenoic acid (DHA), is an omega 3 fatty acid (n-3 FA) that has been shown to play a role in canine growth and physiological integrity and improvements in skin and coat condition. However, potential adverse effects of n-3 FA specifically, impaired cellular immunity has been observed in dogs fed diets with elevated levels of n-3 FA. As such, a safe upper limit (SUL) for total n-3 FAs (DHA and EPA) in dogs has been established. Considering this SUL, sensitive methods detecting DHA in blood serum as a biomarker when conducting n-3 FA supplementation trials involving dogs are required. In this study, an LC-ESI-MS/MS method of DHA detection in dog serum was validated and verified. Recovery of DHA was optimized and parallelism tests were conducted with spiked samples demonstrating that the serum matrix did not interfere with quantitation. The stability of DHA in serum was also investigated, with -80 °C considered suitable when storing samples for up to six months. The method was linear over a calibration range of 1-500 μg/mL and precision and accuracy were found to meet the requirements for validation. This method was verified in an alternative laboratory using a different analytical system and operator, with the results meeting the criteria for verification. Copyright © 2018. Published by Elsevier Inc.

  7. Experience in the use of docosahexaenoic acid (BrudiPlus in patients with increased sperm DNA fragmentation index in Acad. V.I. Kulakov Research Center for Obstetrics, Gynecology and Perinatology

    Directory of Open Access Journals (Sweden)

    A. Yu. Popova

    2015-01-01

    Full Text Available Male factor is the reason of infertility in almost half of marriages. Infertile men have the percentage of sperm with violations of DNA integrity of over 30 %; with that, healthy fertile men have that indicator of less than 15 %. Understanding of importance of damages of sperm DNA is growing with distribution ofauxiliary reproductive technologies. As of today, these consequences have not been studies yet, and the therapeutic effect of intake of antioxidants has not direct correlation with the sperm DNA fragmentation level. Docosahexaenoic acid is one of the most valuable omega-3 polyunsaturated fatty acids for human health. Docosahexaenoic acid is the main component of the brain gray matter, retina, testes, and sperm cell membranes. In connection with that, a study was held the purpose of which was to assess the effect of the nutraceutical enzymatic docosahexaenoic acid triglyceride (BrudiPlus in high concentrations on damaged sperm DNA of patients with idiopathic pathozoospermia. 40 patients with idiopathic pathozoospermia and the level of DNA fragmentation over the statutory value took part in this study. The following positive results were received: intake of BrudiPlus allowed decreasing sperm DNA damages and improving of antioxidant system of sperm. 

  8. Transfer of omega-3 fatty acids across the blood-brain barrier after dietary supplementation with a docosahexaenoic acid-rich omega-3 fatty acid preparation in patients with Alzheimer's disease: the OmegAD study.

    Science.gov (United States)

    Freund Levi, Y; Vedin, I; Cederholm, T; Basun, H; Faxén Irving, G; Eriksdotter, M; Hjorth, E; Schultzberg, M; Vessby, B; Wahlund, L-O; Salem, N; Palmblad, J

    2014-04-01

    Little is known about the transfer of essential fatty acids (FAs) across the human blood-brain barrier (BBB) in adulthood. In this study, we investigated whether oral supplementation with omega-3 (n-3) FAs would change the FA profile of the cerebrospinal fluid (CSF). A total of 33 patients (18 receiving the n-3 FA supplement and 15 receiving placebo) were included in the study. These patients were participants in the double-blind, placebo-controlled randomized OmegAD study in which 204 patients with mild Alzheimer's disease (AD) received 2.3 g n-3 FA [high in docosahexaenoic acid (DHA)] or placebo daily for 6 months. CSF FA levels were related to changes in plasma FA and to CSF biomarkers of AD and inflammation. At 6 months, the n-3 FA supplement group displayed significant increases in CSF (and plasma) eicosapentaenoic acid (EPA), DHA and total n-3 FA levels (P acid were strongly correlated, in contrast to those of DHA. Changes in DHA levels in CSF were inversely correlated with CSF levels of total and phosphorylated tau, and directly correlated with soluble interleukin-1 receptor type II. Thus, the more DHA increased in CSF, the greater the change in CSF AD/inflammatory biomarkers. Oral supplementation with n-3 FAs conferred changes in the n-3 FA profile in CSF, suggesting transfer of these FAs across the BBB in adults. © 2013 The Association for the Publication of the Journal of Internal Medicine.

  9. Synthesis and photophysicochemical studies of a water soluble conjugate between folic acid and zinc tetraaminophthalocyanine

    Energy Technology Data Exchange (ETDEWEB)

    Khoza, Phindile; Antunes, Edith [Department of Chemistry, Rhodes University, PO Box 94, Grahamstown (South Africa); Chen, Ji-Yao [State Key Laboratory of Surface Physics and Department of Physics, Fudan University, Shanghai 200433 (China); Nyokong, Tebello, E-mail: t.nyokong@ru.ac.za [Department of Chemistry, Rhodes University, PO Box 94, Grahamstown (South Africa)

    2013-02-15

    This work reports on the synthesis of zinc tetraaminophthalocyanine (ZnTAPc) functionalized with folic acid (FA), forming ZnTAPcFA. The conjugate between FA and ZnTAPc was soluble in water whereas ZnTAPc alone is not. The structure of ZnTAPcFA conjugate was elucidated by {sup 1}H NMR, MALDI-TOF mass and FTIR spectra. Photophysical and photochemical studies of ZnTAPcFA were conducted in DMSO. The increase in fluorescence quantum yield of the conjugate was accompanied by a decrease in the triplet and singlet oxygen quantum yields. The changes in triplet quantum and singlet oxygen quantum yields were marginal when ZnTAPc was simply mixed with FA without a chemical bond. - Highlights: Black-Right-Pointing-Pointer A conjugate between folic acid and a zinc tetraaminophthalocyanine was formed. Black-Right-Pointing-Pointer The conjugate is water soluble even though the phthalocyanine alone is not. Black-Right-Pointing-Pointer The fluorescence quantum yield of the conjugate was enhanced compared to the phthalocyanine alone. Black-Right-Pointing-Pointer Triplet quantum yields decreased for the conjugate.

  10. Synthesis and photophysicochemical studies of a water soluble conjugate between folic acid and zinc tetraaminophthalocyanine

    International Nuclear Information System (INIS)

    Khoza, Phindile; Antunes, Edith; Chen, Ji-Yao; Nyokong, Tebello

    2013-01-01

    This work reports on the synthesis of zinc tetraaminophthalocyanine (ZnTAPc) functionalized with folic acid (FA), forming ZnTAPcFA. The conjugate between FA and ZnTAPc was soluble in water whereas ZnTAPc alone is not. The structure of ZnTAPcFA conjugate was elucidated by 1 H NMR, MALDI-TOF mass and FTIR spectra. Photophysical and photochemical studies of ZnTAPcFA were conducted in DMSO. The increase in fluorescence quantum yield of the conjugate was accompanied by a decrease in the triplet and singlet oxygen quantum yields. The changes in triplet quantum and singlet oxygen quantum yields were marginal when ZnTAPc was simply mixed with FA without a chemical bond. - Highlights: ► A conjugate between folic acid and a zinc tetraaminophthalocyanine was formed. ► The conjugate is water soluble even though the phthalocyanine alone is not. ► The fluorescence quantum yield of the conjugate was enhanced compared to the phthalocyanine alone. ► Triplet quantum yields decreased for the conjugate

  11. Improved fatty acid analysis of conjugated linoleic acid rich egg yolk triacylglycerols and phospholipid species.

    Science.gov (United States)

    Shinn, Sara; Liyanage, Rohana; Lay, Jack; Proctor, Andrew

    2014-07-16

    Reports from chicken conjugated linoleic acid (CLA) feeding trials are limited to yolk total fatty acid composition, which consistently described increased saturated fatty acids and decreased monounsaturated fatty acids. However, information on CLA triacylglycerol (TAG) and phospholipid (PL) species is limited. This study determined the fatty acid composition of total lipids in CLA-rich egg yolk produced with CLA-rich soy oil, relative to control yolks using gas chromatography with flame ionization detection (GC-FID), determined TAG and PL fatty acid compositions by thin-layer chromatography-GC-FID (TLC-GC-FID), identified intact PL and TAG species by TLC-matrix-assisted laser desorption/ionization mass spectrometry (TLC-MALDI-MS), and determined the composition of TAG and PL species in CLA and control yolks by direct flow infusion electrospray ionization MS (DFI ESI-MS). In total, 2 lyso-phosphatidyl choline (LPC) species, 1 sphingomyelin species, 17 phosphatidyl choline species, 19 TAG species, and 9 phosphatidyl ethanolamine species were identified. Fifty percent of CLA was found in TAG, occurring predominantly in C52:5 and C52:4 TAG species. CLA-rich yolks contained significantly more LPC than did control eggs. Comprehensive lipid profiling may provide insight on relationships between lipid composition and the functional properties of CLA-rich eggs.

  12. Impact of lactic acid bacteria on conjugated linoleic acid content and atherogenic index of butter

    Directory of Open Access Journals (Sweden)

    L Roufegari-Nejad

    2012-11-01

    Full Text Available This is a study aimed to investigate the effect of lactic acid bacteria including Lactobacillus acidophilus and Sterptococcus thermophilus (as thermophilic culture, Lactococcus lactis subsp. lactis, cremoris and diacetylactis, Leuconostoc citrovorum (as mesophilic culture, Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium lactis and a mixed culture of L.acidophilus, L. casei and B. lactis on fatty acid profile, conjugated linoleic acid (CLA and atherogenic index (AI of butter. Fatty acid analysis with gas chromatography indicated that application of thermophilic and mixed culture decreased the ratio of saturated to unsaturated fatty acid; whereas, the butters made with L. acidophilus had the highest content of CLA. Moreover, AI in the samples prepared with thermophilic cultures was the least. Sensory evaluation of the treatments revealed no significant differences (p> 0/05 in appearance and color. However, the butters prepared with thermophilic and mesophilic cultures had more desirable taste in comparison with the samples made with L. acidophilus, L. casei and B. lactis. From the nutritional point of view, the adverse effect of butter could be diminished via the application of selected lactic acid bacteria.

  13. Preparation and Characterization of Self-Assembled Nanoparticles of Hyaluronic Acid-Deoxycholic Acid Conjugates

    Directory of Open Access Journals (Sweden)

    Xuemeng Dong

    2010-01-01

    Full Text Available Novel amphiphilic biopolymers were synthesized using hyaluronic acid (HA as a hydrophilic segment and deoxycholic acid (DOCA as a hydrophobic segment by a 1-ethyl-3-(3-dimethylaminopropyl carbodiimide mediated coupling reaction. The structural characteristics of the HA-DOCA conjugates were investigated using H1 NMR. Self-assembled nanoparticles were prepared based on HA-DOCA conjugates, and its characteristics were investigated using dynamic laser light scattering, transmission electron microscopy (TEM, and fluorescence spectroscopy. The mean diameter was about 293.5 nm with unimodal size distribution in distilled water. The TEM images revealed that the shape of HA-DOCA self-aggregates was spherical. The critical aggregation concentration (CAC was in the range of 0.025–0.056 mg/mL. The partition equilibrium constant (Kv of pyrene in self-aggregates solution was from 1.45×104 to 3.64×104. The aggregation number of DOCA groups per hydrophobic microdomain, estimated by the fluorescence quenching method using cetylpyridinium chloride, increased with increasing degree of substitution.

  14. Lanthanide Lewis acid-mediated enantioselective conjugate radical additions.

    Science.gov (United States)

    Sibi, Mukund P; Manyem, Shankar

    2002-08-22

    [reaction: see text] Lanthanide triflates along with proline-derived ligands have been found to be efficient catalysts for enantioselective conjugate addition of nucleophilic radicals to enoates. N-Acyl oxazolidinones, when used as achiral additives, gave meaningful enhancements in the ees for the product.

  15. Reduction of Burn Progression with Topical Delivery of (Antitumor Necrosis Factor-alpha )-Hyaluronic Acid Conjugates

    Science.gov (United States)

    2012-01-01

    antibody conjugation to HA The conjugation chemistry followed a method previously developed in our laboratory. Briefly, HA (12 mg) was modi - fied...Webster MW, McGill JB, Schwartz SL. Promotion and acceleration of diabetic ulcer healing by arginine-glycine-aspartic acid (RGD) peptide matrix. RGD...Study Group. Diabetes Care 1995; 18: 39–46. 32. Ho-Asjoe M, Chronnell CM, Frame JD, Leigh IM, Carver N. Immunohistochemical analysis of burn depth. J

  16. Physiological function and ecological aspects of fatty acid-amino acid conjugates in insects.

    Science.gov (United States)

    Yoshinaga, Naoko

    2016-07-01

    In tritrophic interactions, plants recognize herbivore-produced elicitors and release a blend of volatile compounds (VOCs), which work as chemical cues for parasitoids or predators to locate their hosts. From detection of elicitors to VOC emissions, plants utilize sophisticated systems that resemble the plant-microbe interaction system. Fatty acid-amino acid conjugates (FACs), a class of insect elicitors, resemble compounds synthesized by microbes in nature. Recent evidence suggests that the recognition of insect elicitors by an ancestral microbe-associated defense system may be the origin of tritrophic interactions mediated by FACs. Here we discuss our findings in light of how plants have customized this defense to be effective against insect herbivores, and how some insects have successfully adapted to these defenses.

  17. Comparison of Fatty Acid Composition in Selected Dietary Supplements Containing Conjugated Linoleic Acid.

    Science.gov (United States)

    Derewiaka, Dorota; Nestorowicz, Klara; Wołosiak, Rafał

    2017-07-04

    The market of pharmaceutical products is offering a wide range of supplements. Most of the consumers believe that these products will improve their state of health, but are they getting what they want and what they are paying for? The aim of the study was to evaluate the quality of selected dietary supplements containing conjugated linoleic acid (CLA). All supplements were available in the Warsaw markets and bought from pharmacies. Assessment of the quality of food supplements was achieved by analysis of fatty acid using gas chromatography coupled with a mass spectrometer. On the basis of the investigations carried out, it was found that content of CLA in selected dietary supplements ranged between 282 and 528 mg by weight of a single capsule. The content of bioactive ingredients found in three of the four product supplements assessed was lower than was claimed by the manufacturer.

  18. Amplified spontaneous emission from the exciplex state of a conjugated polymer "PFO" in oleic acid

    Science.gov (United States)

    Idriss, Hajo; Taha, Kamal K.; Aldaghri, O.; Alhathlool, R.; AlSalhi, M. S.; Ibnaouf, K. H.

    2016-09-01

    The amplified spontaneous emission (ASE) characteristics of a conjugated polymer poly (9, 9-dioctylfluorenyl-2, 7-diyl) (PFO) in oleic acid have been studied under different concentrations and temperatures. Here, the ASE spectra of PFO in oleic acid have been obtained using a transverse cavity configuration where the conjugated PFO was pumped by laser pulses from the third harmonic of Nd: YAG laser (355 nm). The PFO in oleic acid produces ASE from an exciplex state - a new molecular species. The obtained results were compared with the PFO in benzene. Such ASE spectra from the exciplex state have not been observed for the PFO in benzene.

  19. Percoll gradient-centrifuged capacitated mouse sperm have increased fertilizing ability and higher contents of sulfogalactosylglycerolipid and docosahexaenoic acid-containing phosphatidylcholine compared to washed capacitated mouse sperm.

    Science.gov (United States)

    Furimsky, Anna; Vuong, Ngoc; Xu, Hongbin; Kumarathasan, Premkumari; Xu, Min; Weerachatyanukul, Wattana; Bou Khalil, Maroun; Kates, Morris; Tanphaichitr, Nongnuj

    2005-03-01

    Although Percoll gradient centrifugation has been used routinely to prepare motile human sperm, its use in preparing motile mouse sperm has been limited. Here, we showed that Percoll gradient-centrifuged (PGC) capacitated mouse sperm had markedly higher fertilizing ability (sperm-zona pellucida [ZP] binding and in vitro fertilization) than washed capacitated mouse sperm. We also showed that the lipid profiles of PGC capacitated sperm and washed capacitated sperm differed significantly. The PGC sperm had much lower contents of cholesterol and phospholipids. This resulted in relative enrichment of male germ cell-specific sulfogalactosylglycerolipid (SGG), a ZP-binding ligand, in PGC capacitated sperm, and this would explain, in part, their increased ZP-binding ability compared with that of washed capacitated sperm. Analyses of phospholipid fatty acyl chains revealed that PGC capacitated sperm were enriched in phosphatidylcholine (PC) molecular species containing highly unsaturated fatty acids (HUFAs), with docosahexaenoic acid (DHA; C22: 6n-3) being the predominant HUFA (42% of total hydrocarbon chains of PC). In contrast, the level of PC-HUFAs comprising arachidonic acid (20:4n-6), docosapentaenoic acid (C22:5n-6), and DHA in washed capacitated sperm was only 27%. Having the highest unsaturation degree among all HUFAs in PC, DHA would enhance membrane fluidity to the uppermost. Therefore, membranes of PGC capacitated sperm would undergo fertilization-related fusion events at higher rates than washed capacitated sperm. These results suggested that PGC mouse sperm should be used in fertilization experiments and that SGG and DHA should be considered to be important biomarkers for sperm fertilizing ability.

  20. Carrot Juice Administration Decreases Liver Stearoyl-CoA Desaturase 1 and Improves Docosahexaenoic Acid Levels, but Not Steatosis in High Fructose Diet-Fed Weanling Wistar Rats.

    Science.gov (United States)

    Mahesh, Malleswarapu; Bharathi, Munugala; Reddy, Mooli Raja Gopal; Kumar, Manchiryala Sravan; Putcha, Uday Kumar; Vajreswari, Ayyalasomayajula; Jeyakumar, Shanmugam M

    2016-09-01

    Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases associated with an altered lifestyle, besides genetic factors. The control and management of NAFLD mostly depend on lifestyle modifications, due to the lack of a specific therapeutic approach. In this context, we assessed the effect of carrot juice on the development of high fructose-induced hepatic steatosis. For this purpose, male weanling Wistar rats were divided into 4 groups, fed either a control (Con) or high fructose (HFr) diet of AIN93G composition, with or without carrot juice (CJ) for 8 weeks. At the end of the experimental period, plasma biochemical markers, such as triglycerides, alanine aminotransferase, and β-hydroxy butyrate levels were comparable among the 4 groups. Although, the liver injury marker, aspartate aminotransferase, levels in plasma showed a reduction, hepatic triglycerides levels were not significantly reduced by carrot juice ingestion in the HFr diet-fed rats (HFr-CJ). On the other hand, the key triglyceride synthesis pathway enzyme, hepatic stearoyl-CoA desaturase 1 (SCD1), expression at mRNA level was augmented by carrot juice ingestion, while their protein levels showed a significant reduction, which corroborated with decreased monounsaturated fatty acids (MUFA), particularly palmitoleic (C16:1) and oleic (C18:1) acids. Notably, it also improved the long chain n-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA; C22:6) content of the liver in HFr-CJ. In conclusion, carrot juice ingestion decreased the SCD1-mediated production of MUFA and improved DHA levels in liver, under high fructose diet-fed conditions. However, these changes did not significantly lower the hepatic triglyceride levels.

  1. Docosahexaenoic acid induces apoptosis in MCF-7 cells in vitro and in vivo via reactive oxygen species formation and caspase 8 activation.

    Directory of Open Access Journals (Sweden)

    Ki Sung Kang

    Full Text Available BACKGROUND: The present study sought to further investigate the in vitro and in vivo anticancer effects of a representative omega-3 fatty acid, docosahexaenoic acid (DHA, with a focus on assessing the induction of oxidative stress and apoptosis as an important mechanism for its anticancer actions. METHODOLOGY/PRINCIPAL FINDINGS: In vitro studies showed that DHA strongly reduces the viability and DNA synthesis of MCF-7 human breast cancer cells in culture, and also promotes cell death via apoptosis. Mechanistically, accumulation of reactive oxygen species and activation of caspase 8 contribute critically to the induction of apoptotic cell death. Co-presence of antioxidants or selective inhibition or knockdown of caspase 8 each effectively abrogates the cytotoxic effect of DHA. Using athymic nude mice as an in vivo model, we found that feeding animals the 5% fish oil-supplemented diet for 6 weeks significantly reduces the growth of MCF-7 human breast cancer cells in vivo through inhibition of cancer cell proliferation as well as promotion of cell death. Using 3-nitrotyrosine as a parameter, we confirmed that the fish oil-supplemented diet significantly increases oxidative stress in tumor cells in vivo. Analysis of fatty acid content in plasma and tissues showed that feeding animals a 5% fish oil diet increases the levels of DHA and eicosapentaenoic acid in both normal and tumorous mammary tissues by 329% and 300%, respectively. CONCLUSIONS/SIGNIFICANCE: DHA can strongly induce apoptosis in human MCF-7 breast cancer cells both in vitro and in vivo. The induction of apoptosis in these cells is selectively mediated via caspase 8 activation. These observations call for further studies to assess the effectiveness of fish oil as a dietary supplement in the prevention and treatment of human breast cancer.

  2. Deficits in Docosahexaenoic Acid Accrual during Adolescence Reduce Rat Forebrain White Matter Microstructural Integrity: An in vivo Diffusion Tensor Imaging Study.

    Science.gov (United States)

    McNamara, Robert K; Schurdak, Jennifer D; Asch, Ruth H; Peters, Bart D; Lindquist, Diana M

    2018-01-01

    Neuropsychiatric disorders that frequently initially emerge during adolescence are associated with deficits in the omega-3 (n-3) fatty acid docosahexaenoic acid (DHA), elevated proinflammatory signaling, and regional reductions in white matter integrity (WMI). This study determined the effects of altering brain DHA accrual during adolescence on WMI in the rat brain by diffusion tensor imaging (DTI), and investigated the potential mediating role of proinflammatory signaling. During periadolescent development, male rats were fed a diet deficient in n-3 fatty acids (DEF, n = 20), a fish oil-fortified diet containing preformed DHA (FO, n = 20), or a control diet (CON, n = 20). In adulthood, DTI scans were performed and brain WMI was determined using voxelwise tract-based spatial statistics (TBSS). Postmortem fatty acid composition, peripheral (plasma IL-1β, IL-6, and C-reactive protein [CRP]) and central (IL-1β and CD11b mRNA) proinflammatory markers, and myelin basic protein (MBP) mRNA expression were determined. Compared with CON rats, forebrain DHA levels were lower in DEF rats and higher in FO rats. Compared with CON rats, DEF rats exhibited greater radial diffusivity (RD) and mean diffusivity in the right external capsule, and greater axial diffusivity in the corpus callosum genu and left external capsule. DEF rats also exhibited greater RD than FO rats in the right external capsule. Forebrain MBP expression did not differ between groups. Compared with CON rats, central (IL-1β and CD11b) and peripheral (IL-1β and IL-6) proinflammatory markers were not different in DEF rats, and DEF rats exhibited lower CRP levels. These findings demonstrate that deficits in adolescent DHA accrual negatively impact forebrain WMI, independently of elevated proinflammatory signaling. © 2017 S. Karger AG, Basel.

  3. Protein and energy metabolism of young male Wistar rats fed conjugated linoleic acid as structured triacylglycerol

    DEFF Research Database (Denmark)

    Jørgensen, H.; Hansen, C. H.; Mu, Huiling

    2010-01-01

    Twelve 4-week-old male Wistar rats weighing 100 g were fed diets semi-ad libitum for 22 d containing either 1.5% conjugated linoleic acid (CLA-diet) or high oleic sunflower oil (Control-diet). The CLA was structured triacylglycerol with predominantly cis-9, trans-11 and trans-10, cis-12 fatty acid...

  4. The effects of conjugated linoleic acid (CLA) and canola oil on the ...

    African Journals Online (AJOL)

    Dietary conjugated linoleic acid (CLA) causes adverse effects on quality of eggs by modifying the fatty acid composition of the yolk. Supplementing oils prevent CLA-induced changes, but cause a decrease in the level of egg CLA. The objective of the study was to investigate the incorporation of CLA into the egg and its effect ...

  5. Effect of dietary conjugated linoleic acid (CLA) on the growth and ...

    African Journals Online (AJOL)

    Effect of dietary conjugated linoleic acid (CLA) on the growth and lipid metabolism of geese and fatty acid composition of their tissues. ... Dietary CLA altered serum lipid concentrations by decreasing total cholesterol, triglyceride and low density lipoprotein-cholesterol concentrations, the atherogenic index and activity of ...

  6. Characterization of hapten-protein conjugates: antibody generation and immunoassay development for chlorophenoxyacetic acid pesticides.

    Science.gov (United States)

    Boro, Robin C; Singh, K Vikas; Suri, C Raman

    2009-01-01

    The generation of specific and sensitive antibodies against small molecules is greatly dependent upon the characteristics of the hapten-protein conjugates. In this study, we report a new fluorescence-based method for the characterization of hapten-protein conjugates. The method is based on an effect promoted by hapten-protein conjugation density upon the fluorescence intensity of the intrinsic tryptophan chromophore molecules of the protein. The proposed methodology is applied to quantify the hapten-protein conjugation density for two different chlorophenoxyacetic acid pesticides, 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4-dichlorophenoxybutyric acid (2,4-DB), coupled to carrier protein. Highly sensitive anti-2,4-D and anti-2,4-DB antibodies were obtained using these well-characterized hapten-protein conjugates. The generated antibodies were used in an immunoassay format demonstrating inhibitory concentration (IC50) values equal to 30 and 7 ng/mL for 2,4-D and 2,4-DB, respectively. Linearity was observed in the concentration range between 0.1-500 nglmL with LODs around 4 and 3 ng/mL for 2,4-D and 2,4-DB, respectively, in standard water samples. The proposed method was successfully applied for the determination of the extent of hapten-protein conjugation to produce specific antibodies for immunoassay development against pesticides.

  7. Biotransformation of Flavonoid Conjugates with Fatty Acids and Evaluations of Their Functionalities

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    Cynthia Q. Sun

    2017-11-01

    Full Text Available Enzymatic conjugation with fatty acids including omega-3 polyunsaturated fatty acids (ω-3 PUFAs derived from fish oil to three citrus fruit-derived flavonoids: grapefruit extract, naringin, and neohesperidin dihydrochalcone were investigated. The conversions were achieved over 85% under the catalysis of lipase Novozyme 435 in acetone at 45°C at semi-preparative scale. The conjugates were purified via solvent partition and silica gel chromatography and achieved 90–98% in purity. The NMR analysis of the conjugates confirmed that the fatty acid carbon chain was linked onto the primary –OH group on the glucose moiety of the flavonoids. The purified flavonoid conjugates alongside their original flavonoids were analyzed for antioxidant activities via 2,2-diphenyl-1-picrylhydrazyl scavenging assay, and anti-peroxidation test via peroxide values measured during a 1-week fish oil storage trial. Vascular endothelial growth factor (VEGF assay was conducted with 1, 10, and 100 μM of naringin and grapefruits and their conjugates, respectively, and total VEGF levels were measured at 24 and 48 h, respectively, using ELISA and dot blot analysis. The results from these functionality experiments demonstrated that flavonoid FA conjugates have at least comparable (if not higher antioxidant activity, anti-peroxidation activity, and anti-angiogenic activity.

  8. Constitutive ω-3 fatty acid production in fat-1 transgenic mice and docosahexaenoic acid administration to wild type mice protect against 2,4,6-trinitrobenzene sulfonic acid-induced colitis.

    Science.gov (United States)

    Yum, Hye-Won; Kang, Jing X; Hahm, Ki Baik; Surh, Young-Joon

    2017-06-10

    Omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) are known to have strong anti-inflammatory effects. In the present study, we investigated the protective effects of ω-3 PUFAs on experimentally induced murine colitis. Intrarectal administration of 2.5% 2,4,6-trinitrobenzene sulfonic acid (TNBS) caused inflammation in the colon of wild type mice, but this was less severe in fat-1 transgenic mice that constitutively produce ω-3 PUFAs from ω-6 PUFAs. The intraperitoneal administration of docosahexaenoic acid (DHA), a representative ω-3 PUFA, was also protective against TNBS-induced murine colitis. In addition, endogenously formed and exogenously introduced ω-3 PUFAs attenuated the production of malondialdehyde and 4-hydroxynonenal in the colon of TNBS-treated mice. The effective protection against inflammatory and oxidative colonic tissue damages in fat-1 and DHA-treated mice was associated with suppression of NF-κB activation and cyclooxygenase-2 expression and with elevated activation of Nrf2 and upregulation of its target gene, heme oxygenase-1. Taken together, these results provide mechanistic basis of protective action of ω-3 fatty PUFAs against experimental colitis. Copyright © 2017. Published by Elsevier Inc.

  9. The content of docosahexaenoic acid in the suckling and the weaning diet beneficially modulates the ability of immune cells to response to stimuli.

    Science.gov (United States)

    Richard, Caroline; Lewis, Erin D; Goruk, Susan; Field, Catherine J

    2016-09-01

    The objective of the study was to isolate the effect of feeding a diet supplemented with docosahexaenoic acid (DHA) during the suckling and/or the weaning period on immune system development and function in offspring. Dams were randomized to one of two nutritionally adequate diets: control diet (N=12, 0% DHA) or DHA diet (N=8, 0.9% DHA). Diets were fed to dams throughout lactation, and then at weaning (21d), two pups per dam were randomly assigned to continue on the same diet as the dam or consume the other experimental diet for an additional 21d. At 6 weeks, splenocyte phenotypes and ex vivo cytokine production after stimulation with concanavalin A (ConA), lipopolysaccharide (LPS) or ovalbumin were assessed. Pups who received the control diet during both periods had the lowest production of IL-2 after ConA (Pdiet (Pdiet, resulted in a lower production of IL-1β and TNF-α in LPS-stimulated splenocytes and a higher proportion of total CD27+ cells (all Pdiet during weaning led to a lower TNF-α and IL-1β response to a bacterial antigen. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Docosahexaenoic Acid Inhibits Tumor Promoter-Induced Urokinase-Type Plasminogen Activator Receptor by Suppressing PKCδ- and MAPKs-Mediated Pathways in ECV304 Human Endothelial Cells.

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    Sen Lian

    Full Text Available The overexpression of urokinase-type plasminogen activator receptor (uPAR is associated with inflammation and virtually all human cancers. Despite the fact that docosahexaenoic acid (DHA has been reported to possess anti-inflammatory and anti-tumor properties, the negative regulation of uPAR by DHA is still undefined. Here, we investigated the effect of DHA on 12-O-tetradecanoylphorbol-13-acetate (TPA-induced uPAR expression and the underlying molecular mechanisms in ECV304 human endothelial cells. DHA concentration-dependently inhibited TPA-induced uPAR. Specific inhibitors and mutagenesis studies showed that PKCδ, JNK1/2, Erk1/2, NF-κB, and AP-1 were critical for TPA-induced uPAR expression. Application of DHA suppressed TPA-induced translocation of PKCδ, activation of the JNK1/2 and Erk1/2 signaling pathways, and subsequent AP-1 and NF-κB transactivation. In conclusion, these observations suggest a novel role for DHA in reducing uPAR expression and cell invasion by inhibition of PKCδ, JNK1/2, and Erk1/2, and the reduction of AP-1 and NF-κB activation in ECV304 human endothelial cells.

  11. Application of the Response Surface Methodology to Optimize the Fermentation Parameters for Enhanced Docosahexaenoic Acid (DHA) Production by Thraustochytrium sp. ATCC 26185.

    Science.gov (United States)

    Wu, Kang; Ding, Lijian; Zhu, Peng; Li, Shuang; He, Shan

    2018-04-22

    The aim of this study was to determine the cumulative effect of fermentation parameters and enhance the production of docosahexaenoic acid (DHA) by Thraustochytrium sp. ATCC 26185 using response surface methodology (RSM). Among the eight variables screened for effects of fermentation parameters on DHA production by Plackett-Burman design (PBD), the initial pH, inoculum volume, and fermentation volume were found to be most significant. The Box-Behnken design was applied to derive a statistical model for optimizing these three fermentation parameters for DHA production. The optimal parameters for maximum DHA production were initial pH: 6.89, inoculum volume: 4.16%, and fermentation volume: 140.47 mL, respectively. The maximum yield of DHA production was 1.68 g/L, which was in agreement with predicted values. An increase in DHA production was achieved by optimizing the initial pH, fermentation, and inoculum volume parameters. This optimization strategy led to a significant increase in the amount of DHA produced, from 1.16 g/L to 1.68 g/L. Thraustochytrium sp. ATCC 26185 is a promising resource for microbial DHA production due to the high-level yield of DHA that it produces, and the capacity for large-scale fermentation of this organism.

  12. Impact of carbon and nitrogen feeding strategy on high production of biomass and docosahexaenoic acid (DHA) by Schizochytrium sp. LU310.

    Science.gov (United States)

    Ling, Xueping; Guo, Jing; Liu, Xiaoting; Zhang, Xia; Wang, Nan; Lu, Yinghua; Ng, I-Son

    2015-05-01

    A new isolated Schizochytrium sp. LU310 from the mangrove forest of Wenzhou, China, was found as a high producing microalga of docosahexaenoic acid (DHA). In this study, the significant improvements for DHA fermentation by the batch mode in the baffled flasks (i.e. higher oxygen supply) were achieved. By applied the nitrogen-feeding strategy in 1000 mL baffled flasks, the biomass, DHA concentration and DHA productivity were increased by 110.4%, 117.9% and 110.4%, respectively. Moreover, DHA concentration of 21.06 g/L was obtained by feeding 15 g/L of glucose intermittently, which was an increase of 41.25% over that of the batch mode. Finally, an innovative strategy was carried out by intermittent feeding carbon and simultaneously feeding nitrogen. The maximum DHA concentration and DHA productivity in the fed-batch cultivation reached to 24.74 g/L and 241.5 mg/L/h, respectively. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Effect of docosahexaenoic acid on hippocampal neurons in high-glucose condition: involvement of PI3K/AKT/nuclear factor-κB-mediated inflammatory pathways.

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    Yang, R-H; Lin, J; Hou, X-H; Cao, R; Yu, F; Liu, H-Q; Ji, A-L; Xu, X-N; Zhang, L; Wang, F

    2014-08-22

    Accumulating evidence suggested that hyperglycemia played a critical role in hippocampus dysfunction in patients with diabetes mellitus. However, the multifactorial pathogenesis of hyperglycemia-induced impairments of hippocampal neurons has not been fully elucidated. Docosahexaenoic acid (DHA) has been shown to enhance learning and memory and affect neural function in various experimental conditions. The present study investigated the effects of DHA on the lipid peroxidation, the level of inflammatory cytokines and neuron apoptosis in the hippocampal neurons in high-glucose condition. High-glucose administration increased the level of tumor necrosis factor α (TNF-α) and IL-6, induced oxidative stress and apoptosis of hippocampal neurons in vitro. DHA treatment reduced oxidative stress and TNF-α expression, protected the hippocampal neurons by increasing AKT phosphorylation and decreasing caspase-3 and caspase-9 expression. These results suggested that high-glucose exposure induced injury of hippocampal neurons in vitro, and the principle mechanisms involved in the neuroprotective effect of DHA were its antioxidant and anti-apoptotic potential. DHA may thus be of use in preventing or treating neuron-degeneration resulting from hyperglycemia. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. Docosahexaenoic acid (DHA) accretion in the placenta but not the fetus is matched by plasma unesterified DHA uptake rates in pregnant Long Evans rats.

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    Metherel, Adam H; Kitson, Alex P; Domenichiello, Anthony F; Lacombe, R J Scott; Hopperton, Kathryn E; Trépanier, Marc-Olivier; Alashmali, Shoug M; Lin, Lin; Bazinet, Richard P

    2017-10-01

    Maternal delivery of docosahexaenoic acid (DHA, 22:6n-3) to the developing fetus via the placenta is required for fetal neurodevelopment, and is the only mechanism by which DHA can be accreted in the fetus. The aim of the current study was to utilize a balance model of DHA accretion combined with kinetic measures of serum unesterified DHA uptake to better understand the mechanism by which maternal DHA is delivered to the fetus via the placenta. Female rats maintained on a 2% α-linolenic acid diet free of DHA for 56 days were mated, and for balance analysis, sacrificed at 18 days of pregnancy, and fetus, placenta and maternal carcass fatty acid concentration were determined. For tissue DHA uptake, pregnant dams (14-18 days) were infused for 5 min with radiolabeled 14 C-DHA and kinetic modeling was used to determine fetal and placental serum unesterified DHA uptake rates. DHA accretion rates in the fetus were determined to be 38 ± 2 nmol/d/g, 859 ± 100 nmol/d/litter and 74 ± 3 nmol/d/pup, which are all higher (P  0.05) in placental DHA accretion rates versus serum unesterified DHA uptake rates were observed as values varied only 6-35% between studies. No differences in placental accretion and uptake rates suggests that serum unesterified DHA is a significant pool for the maternal-placental transfer of DHA, and lower fetal DHA uptake compared to accretion supports remodeling of placental DHA for delivery to the fetus. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Docosahexaenoic acid modifies the clustering and size of lipid rafts and the lateral organization and surface expression of MHC class I of EL4 cells.

    Science.gov (United States)

    Shaikh, Saame Raza; Rockett, Benjamin Drew; Salameh, Muhammad; Carraway, Kristen

    2009-09-01

    An emerging molecular mechanism by which docosahexaenoic acid (DHA) exerts its effects is modification of lipid raft organization. The biophysical model, based on studies with liposomes, shows that DHA avoids lipid rafts because of steric incompatibility between DHA and cholesterol. The model predicts that DHA does not directly modify rafts; rather, it incorporates into nonrafts to modify the lateral organization and/or conformation of membrane proteins, such as the major histocompatibility complex (MHC) class I. Here, we tested predictions of the model at a cellular level by incorporating oleic acid, eicosapentaenoic acid (EPA), and DHA, compared with a bovine serum albumin (BSA) control, into the membranes of EL4 cells. Quantitative microscopy showed that DHA, but not EPA, treatment, relative to the BSA control diminished lipid raft clustering and increased their size. Approximately 30% of DHA was incorporated directly into rafts without changing the distribution of cholesterol between rafts and nonrafts. Quantification of fluorescence colocalization images showed that DHA selectively altered MHC class I lateral organization by increasing the fraction of the nonraft protein into rafts compared with BSA. Both DHA and EPA treatments increased antibody binding to MHC class I compared with BSA. Antibody titration showed that DHA and EPA did not change MHC I conformation but increased total surface levels relative to BSA. Taken together, our findings are not in agreement with the biophysical model. Therefore, we propose a model that reconciles contradictory viewpoints from biophysical and cellular studies to explain how DHA modifies lipid rafts on several length scales. Our study supports the notion that rafts are an important target of DHA's mode of action.

  16. Pd(II)/Bipyridine-Catalyzed Conjugate Addition of Arylboronic Acids to α,β-Unsaturated Carboxylic Acids. Synthesis of β-Quaternary Carbons Substituted Carboxylic Acids.

    Science.gov (United States)

    Liu, Rui; Yang, Zhenyu; Ni, Yuxin; Song, Kaixuan; Shen, Kai; Lin, Shaohui; Pan, Qinmin

    2017-08-04

    Pd(II)/bipyridine-catalyzed conjugate addition of arylboronic acids to α,β-unsaturated carboxylic acids (including β,β-disubstituted acrylic acids) was developed and optimized, which provided a mild and convenient method for the highly challenging synthesis of β-quaternary carbons substituted carboxylic acids.

  17. Conjugated Linoleic Acid (CLA) content in different tissues of ruminants fed with CLA supplementation

    OpenAIRE

    Pellattiero, Erika

    2014-01-01

    Conjugated Linoleic Acid (CLA) are a group of positional and geometric isomers of Linoleic Acid characterized by a carbon chain containing 18 carbon atoms and two double bonds, not in the classic position (cis), but conjugated from the carbons atoms 9, 10 or 11. Double bonds have different position in the carbon chain ([7,9], [8,10], [9,11], [10,12], [11,13] and [12,14]) and four different geometric distribution (cis/trans, trans/cis, cis/cis and trans/trans). In total 24 possible isomers are...

  18. Docosahexaenoic acid for reading, working memory and behavior in UK children aged 7-9: A randomized controlled trial for replication (the DOLAB II study.

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    Paul Montgomery

    Full Text Available Omega-3 fatty acids are central to brain-development of children. Evidence from clinical trials and systematic reviews demonstrates the potential of long-chain Omega-3 supplementation for learning and behavior. However, findings are inconclusive and in need of robust replication studies since such work is lacking.Replication of the 2012 DOLAB 1 study findings that a dietary supplementation with the long-chain omega-3 docosahexaenoic acid (DHA had beneficial effects on the reading, working memory, and behavior of healthy schoolchildren.Parallel group, fixed-dose, randomized (minimization, 30% random element, double-blind, placebo-controlled trial (RCT.Mainstream primary schools (n = 84 from five counties in the UK in 2012-2015.Healthy children aged 7-9 underperforming in reading (<20th centile. 1230 invited, 376 met study criteria.600 mg/day DHA (from algal oil, placebo: taste/color matched corn/soybean oil; for 16 weeks.Age-standardized measures of reading, working memory, and behavior, parent-rated and as secondary outcome teacher-rated.376 children were randomized. Reading, working memory, and behavior change scores showed no consistent differences between intervention and placebo group. Some behavioral subscales showed minor group differences.This RCT did not replicate results of the earlier DOLAB 1 study on the effectiveness of nutritional supplementation with DHA for learning and behavior. Possible reasons are discussed, particularly regarding the replication of complex interventions.www.controlled-trials.com (ISRCTN48803273 and protocols.io (https://dx.doi.org/10.17504/protocols.io.k8kczuw.

  19. Docosahexaenoic acid for reading, cognition and behavior in children aged 7-9 years: a randomized, controlled trial (the DOLAB Study.

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    Alexandra J Richardson

    Full Text Available Omega-3 fatty acids are dietary essentials, and the current low intakes in most modern developed countries are believed to contribute to a wide variety of physical and mental health problems. Evidence from clinical trials indicates that dietary supplementation with long-chain omega-3 may improve child behavior and learning, although most previous trials have involved children with neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD or developmental coordination disorder (DCD. Here we investigated whether such benefits might extend to the general child population.To determine the effects of dietary supplementation with the long-chain omega-3 docosahexaenoic acid (DHA on the reading, working memory, and behavior of healthy schoolchildren.Parallel group, fixed-dose, randomized, double-blind, placebo-controlled trial (RCT.Mainstream primary schools in Oxfordshire, UK (n = 74.Healthy children aged 7-9 years initially underperforming in reading (≤ 33(rd centile. 1376 invited, 362 met study criteria.600 mg/day DHA (from algal oil, or taste/color matched corn/soybean oil placebo.Age-standardized measures of reading, working memory, and parent- and teacher-rated behavior.ITT analyses showed no effect of DHA on reading in the full sample, but significant effects in the pre-planned subgroup of 224 children whose initial reading performance was ≤ 20(th centile (the target population in our original study design. Parent-rated behavior problems (ADHD-type symptoms were significantly reduced by active treatment, but little or no effects were seen for either teacher-rated behaviour or working memory.DHA supplementation appears to offer a safe and effective way to improve reading and behavior in healthy but underperforming children from mainstream schools. Replication studies are clearly warranted, as such children are known to be at risk of low educational and occupational outcomes in later life.ClinicalTrials.gov NCT01066182

  20. Docosahexaenoic Acid Modulates a HER2-Associated Lipogenic Phenotype, Induces Apoptosis, and Increases Trastuzumab Action in HER2-Overexpressing Breast Carcinoma Cells

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    Graziela Rosa Ravacci

    2015-01-01

    Full Text Available In breast cancer, lipid metabolic alterations have been recognized as potential oncogenic stimuli that may promote malignancy. To investigate whether the oncogenic nature of lipogenesis closely depends on the overexpression of HER2 protooncogene, the normal breast cell line, HB4a, was transfected with HER2 cDNA to obtain HER2-overexpressing HB4aC5.2 cells. Both cell lines were treated with trastuzumab and docosahexaenoic acid. HER2 overexpression was accompanied by an increase in the expression of lipogenic genes involved in uptake (CD36, transport (FABP4, and storage (DGAT of exogenous fatty acids (FA, as well as increased activation of “de novo” FA synthesis (FASN. We further investigate whether this lipogenesis reprogramming might be regulated by mTOR/PPARγ pathway. Inhibition of the mTORC1 pathway markers, p70S6 K1, SREBP1, and LIPIN1, as well as an increase in DEPTOR expression (the main inhibitor of the mTOR was detected in HB4aC5.2. Based on these results, a PPARγ selective antagonist, GW9662, was used to treat both cells lines, and the lipogenic genes remained overexpressed in the HB4aC5.2 but not HB4a cells. DHA treatment inhibited all lipogenic genes (except for FABP4 in both cell lines yet only induced death in the HB4aC5.2 cells, mainly when associated with trastuzumab. Neither trastuzumab nor GW9662 alone was able to induce cell death. In conclusion, oncogenic transformation of breast cells by HER2 overexpression may require a reprogramming of lipogenic genetic that is independent of mTORC1 pathway and PPARγ activity. This reprogramming was inhibited by DHA.

  1. Docosahexaenoic Acid Modulates a HER2-Associated Lipogenic Phenotype, Induces Apoptosis, and Increases Trastuzumab Action in HER2-Overexpressing Breast Carcinoma Cells.

    Science.gov (United States)

    Ravacci, Graziela Rosa; Brentani, Maria Mitzi; Tortelli, Tharcisio Citrângulo; Torrinhas, Raquel Suzana M M; Santos, Jéssica Reis; Logullo, Angela Flávia; Waitzberg, Dan Linetzky

    2015-01-01

    In breast cancer, lipid metabolic alterations have been recognized as potential oncogenic stimuli that may promote malignancy. To investigate whether the oncogenic nature of lipogenesis closely depends on the overexpression of HER2 protooncogene, the normal breast cell line, HB4a, was transfected with HER2 cDNA to obtain HER2-overexpressing HB4aC5.2 cells. Both cell lines were treated with trastuzumab and docosahexaenoic acid. HER2 overexpression was accompanied by an increase in the expression of lipogenic genes involved in uptake (CD36), transport (FABP4), and storage (DGAT) of exogenous fatty acids (FA), as well as increased activation of "de novo" FA synthesis (FASN). We further investigate whether this lipogenesis reprogramming might be regulated by mTOR/PPARγ pathway. Inhibition of the mTORC1 pathway markers, p70S6 K1, SREBP1, and LIPIN1, as well as an increase in DEPTOR expression (the main inhibitor of the mTOR) was detected in HB4aC5.2. Based on these results, a PPARγ selective antagonist, GW9662, was used to treat both cells lines, and the lipogenic genes remained overexpressed in the HB4aC5.2 but not HB4a cells. DHA treatment inhibited all lipogenic genes (except for FABP4) in both cell lines yet only induced death in the HB4aC5.2 cells, mainly when associated with trastuzumab. Neither trastuzumab nor GW9662 alone was able to induce cell death. In conclusion, oncogenic transformation of breast cells by HER2 overexpression may require a reprogramming of lipogenic genetic that is independent of mTORC1 pathway and PPARγ activity. This reprogramming was inhibited by DHA.

  2. Docosahexaenoic acid signaling modulates cell survival in experimental ischemic stroke penumbra and initiates long-term repair in young and aged rats.

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    Tiffany N Eady

    Full Text Available Docosahexaenoic acid, a major omega-3 essential fatty acid family member, improves behavioral deficit and reduces infarct volume and edema after experimental focal cerebral ischemia. We hypothesize that DHA elicits neuroprotection by inducing AKT/p70S6K phosphorylation, which in turn leads to cell survival and protects against ischemic stroke in young and aged rats.Rats underwent 2 h of middle cerebral artery occlusion (MCAo. DHA, neuroprotectin D1 (NPD1 or vehicle (saline was administered 3 h after onset of stroke. Neurological function was evaluated on days 1, 2, 3, and 7. DHA treatment improved functional recovery and reduced cortical, subcortical and total infarct volumes 7 days after stroke. DHA also reduced microglia infiltration and increased the number of astrocytes and neurons when compared to vehicle on days 1 and 7. Increases in p473 AKT and p308 AKT phosphorylation/activation were observed in animals treated with DHA 4 h after MCAo. Activation of other members of the AKT signaling pathway were also observed in DHA treated animals including increases in pS6 at 4 h and pGSK at 24 h. DHA or NPD1 remarkably reduced total and cortical infarct in aged rats. Moreover, we show that in young and aged rats DHA treatment after MCAo potentiates NPD1 biosynthesis. The phosphorylation of p308 AKT or pGSK was not different between groups in aged rats. However, pS6 expression was increased with DHA or NPD1 treatment when compared to vehicle.We suggest that DHA induces cell survival, modulates the neuroinflammatory response and triggers long term restoration of synaptic circuits. Both DHA and NPD1 elicited remarkable protection in aged animals. Accordingly, activation of DHA signaling might provide benefits in the management of ischemic stroke both acutely as well as long term to limit ensuing disabilities.

  3. Dietary docosahexaenoic acid-induced generation of liver lipid peroxides is not suppressed further by elevated levels of glutathione in ODS rats.

    Science.gov (United States)

    Sekine, Seiji; Kubo, Kazuhiro; Tadokoro, Tadahiro; Saito, Morio

    2006-04-01

    We examined the effects of ascorbic acid (AsA) and glutathione (GSH; experiment 1) and of GSH in acetaminophen-fed rats (experiment 2) on dietary docosahexaenoic acid (DHA)-induced tissue lipid peroxidation. In experiment 1, AsA-requiring Osteogenic Disorder Shionogi/Shi-od/od (ODS) rats were fed soybean protein diets containing DHA (10.0% total energy) and AsA at 50 (low) or 300 (normal) mg/kg without (low) or with (normal) methionine at 2 g/kg for 32 d. In experiment 2, ODS rats were fed diets containing DHA (7.8% total energy) and acetaminophen (4 g/kg) with different levels of dietary methionine (low, moderate, high, and excessive at 0, 3, 6, and 9 g/kg, respectively) for 30 d. Tissue lipid peroxides and antioxidant levels were determined. In experiment 1, liver lipid peroxide levels in the low-AsA group were lower than those in the normal-AsA group, but kidney and testis lipid peroxide levels in the low-AsA group were higher than those in the normal-AsA group. Dietary methionine tended to decrease tissue lipid peroxide levels but did not decrease vitamin E (VE) consumption. In experiment 2, a high level of methionine (6 g/kg) decreased liver lipid peroxide levels and VE consumption. However, generation of tissue lipid peroxides and VE consumption were not decreased further by a higher dose of methionine (9 g/kg). Higher than normal levels of dietary methionine are not necessarily associated with decreased dietary DHA-induced generation of tissue lipid peroxides and VE consumption except that the GSH requirement is increased in a condition such as acetaminophen feeding.

  4. Role of Choline-Docosahexaenoic acid and Trigonella foenum graecum Seed Extract on Ovariectomy Induced Dyslipidemia and Oxidative Stress in Rat Model

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    Nagamma Takkella

    2018-01-01

    Full Text Available Background: Menopause is characterized by the deficiency of ovarian hormones, mainly estrogen. The decline in estrogen hormone is contributing the cardiovascular disorders in women. Hormone replacement therapy has disadvantages especially a higher risk of breast, ovarian and endometrial cancers upon chronic use. Phytoestrogens may be used as an alternative to hormone replacement therapy. Aim and Objectives: This study was designed to scientifically evaluate the role of Choline- Docosahexaenoic Acid (DHA and Trigonella foenum graecum (TFG seed extract on Ovariectomy (OVX induced dyslipidemia and oxidative stress in rat model. Material and Methods: Female Wistar rats were allocated into four groups (n=6:1 Sham control, 2 ovariectomized, 3 ovariectomized+ choline-DHA and 4 ovariectomized + choline-DHA+TFG. After 30 days of treatment, fasting blood samples and liver tissues were collected. Serum was analyzed for lipid profile and liver homogenates were used for assessment of oxidative stress and antioxidant activity. Results: Ovariectomized rats showed significantly increased (P<0.05 Total Cholesterol (TC, Low Density Lipoprotein (LDL levels and decreased High Density Lipoprotein (HDL levels. Treating ovariectomized rats with choline-DHA and TFG seed extract significantly lowered (P<0.05 total cholesterol, LDL and markedly increased the HDL. Significantly increased (P≤0.01 Thiobarbituric Acid Reactive Substances (TBARS and reduced (P<0.05 glutathione levels were observed in OVX group. The synergetic effect of choline-DHA and fenugreek showed a significant reduction ((P≤0.01 in TBARS levels. Conclusion: These results showed that choline-DHA with TFG supplementation have a favorable effect on OVX induced hyperlipidemia and oxidative stress. Therefore, these components may be a therapeutic agent for treating the menopause induced hyperlipidemia or oxidative stress.

  5. Conjugated linoleic acid as a potential protective factor in prevention of breast cancer 

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    Agnieszka Białek

    2013-01-01

    Full Text Available Cancers are the second leading cause of deaths in Poland, among both women and men. Breast cancer is the malignancy most frequently diagnosed in women. In 2008 mammary cancer was diagnosed in up to 14 500 patients. It is also the second most common cause of cancer deaths among women in our country. Although the etiology of most cases of this disease is not known, risk factors include a variety of nutritional factors. The amount of fat consumed in the diet and the quantity and quality of fatty acids are especially crucial. Among fatty acids to which great importance in modification of cancer risk is attributed are conjugated linoleic acid. Conjugated linoleic acids (CLA are a group of positional and geometric isomers of linoleic acid, with a conjugated double bond system in the carbon chain. The main natural source of them is milk and dairy products and meat of different species of ruminants, in which cis-9, trans-11 octadecadienoic acid (rumenic acid occurs in the largest quantities, constituting over 90�0of the total pool of CLA. Another important isomer is trans-10, cis-12 octadecadienoic acid, which occurs with rumenic acid in dietary supplements, usually in the ratio 1:1. Surveys conducted show their possible health promoting effects in obesity, atherosclerosis, cardiovascular diseases, osteoporosis, diabetes, insulin resistance, inflammation, and various types of cancer, especially breast cancer. 

  6. Characterization of Free, Conjugated, and Bound Phenolic Acids in Seven Commonly Consumed Vegetables

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    Yuan Gao

    2017-11-01

    Full Text Available Phenolic acids are thought to be beneficial for human health and responsible for vegetables’ health-promoting properties. Free, conjugated, and bound phenolic acids of seven commonly consumed vegetables, including kidney bean, cow pea, snow pea, hyacinth bean, green soy bean, soybean sprouts and daylily, from the regions of Beijing, Hangzhou, and Guangzhou, were identified and quantified by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS. Three vegetables, namely green soy bean, soybean sprouts, and daylily (Hemerocallis fulva L., from the Beijing region contained higher concentrations of total phenolic acids than those from the Hangzhou and Guangzhou regions. The results indicated that the phenolic acid content in the seven vegetables appeared to be species-dependent. The highest content of phenolic acids was found in daylily, followed by green soy bean, while the least amounts were identified in kidney bean and hyacinth bean. Typically, phenolic acids are predominantly found in conjugated forms. Principle component analysis (PCA revealed some key compounds that differentiated the seven vegetables. Green soy bean, compared to the other six vegetables, was characterized by higher levels of syringic acid, ferulic acid, vanillic acid, and sinapic acid. Other compounds, particularly p-coumaric acid, neochlorogenic acid, and caffeic acid, exhibited significantly higher concentrations in daylily. In addition, p-coumaric acid was the characteristic substance in cow pea. Results from this study can contribute to the development of vegetables with specific phytochemicals and health benefits.

  7. Characterization of Free, Conjugated, and Bound Phenolic Acids in Seven Commonly Consumed Vegetables.

    Science.gov (United States)

    Gao, Yuan; Ma, Shuai; Wang, Meng; Feng, Xiao-Yuan

    2017-11-01

    Phenolic acids are thought to be beneficial for human health and responsible for vegetables' health-promoting properties. Free, conjugated, and bound phenolic acids of seven commonly consumed vegetables, including kidney bean, cow pea, snow pea, hyacinth bean, green soy bean, soybean sprouts and daylily, from the regions of Beijing, Hangzhou, and Guangzhou, were identified and quantified by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Three vegetables, namely green soy bean, soybean sprouts, and daylily ( Hemerocallis fulva L.), from the Beijing region contained higher concentrations of total phenolic acids than those from the Hangzhou and Guangzhou regions. The results indicated that the phenolic acid content in the seven vegetables appeared to be species-dependent. The highest content of phenolic acids was found in daylily, followed by green soy bean, while the least amounts were identified in kidney bean and hyacinth bean. Typically, phenolic acids are predominantly found in conjugated forms. Principle component analysis (PCA) revealed some key compounds that differentiated the seven vegetables. Green soy bean, compared to the other six vegetables, was characterized by higher levels of syringic acid, ferulic acid, vanillic acid, and sinapic acid. Other compounds, particularly p -coumaric acid, neochlorogenic acid, and caffeic acid, exhibited significantly higher concentrations in daylily. In addition, p -coumaric acid was the characteristic substance in cow pea. Results from this study can contribute to the development of vegetables with specific phytochemicals and health benefits.

  8. Surface conjugation of poly (dimethyl siloxane) with itaconic acid-based materials for antibacterial effects

    Science.gov (United States)

    Birajdar, Mallinath S.; Cho, Hyunjoo; Seo, Youngmin; Choi, Jonghoon; Park, Hansoo

    2018-04-01

    Poly (dimethyl siloxane) (PDMS) is widely used in various biomedical applications. However, the PDMS surface is known to cause bacterial adhesion and protein absorption issues due to its high hydrophobicity. Therefore, the development of antibacterial and anti-protein products is necessary to prevent these problems. In this study, to improve its antibacterial property and prevent protein adsorption, PDMS surfaces were conjugated with itaconic acid (IA) and poly (itaconic acid) (PIA) via a chemical method. Additionally, IA and PIA were physically blended with PDMS to compare the antibacterial properties of these materials with those of the chemically conjugated PDMS surfaces. The successful synthesis of the PIA polymer structure was confirmed by proton nuclear magnetic resonance (1H NMR) spectroscopy. The successful conjugation of IA and PIA on PDMS was confirmed by attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), water contact angle measurements, and microbicinchoninic acid (BCA) protein assay analyses. The PDMS surfaces functionalized with IA and PIA by the conjugation method better prevented protein adsorption than the bare PDMS. Therefore, these surface-conjugated PDMS can be used in various biomedical applications.

  9. A novel liquid chromatography/tandem mass spectrometry (LC-MS/MS) based bioanalytical method for quantification of ethyl esters of Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) and its application in pharmacokinetic study.

    Science.gov (United States)

    Viswanathan, Sekarbabu; Verma, P R P; Ganesan, Muniyandithevar; Manivannan, Jeganathan

    2017-07-15

    Omega-3 fatty acids are clinically useful and the two marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are prevalent in fish and fish oils. Omega-3 fatty acid formulations should undergo a rigorous regulatory step in order to obtain United States Food and Drug Administration (USFDA) approval as prescription drug. In connection with that, despite quantifying EPA and DHA fatty acids, there is a need for quantifying the level of ethyl esters of them in biological samples. In this study, we make use of reverse phase high performance liquid chromatography coupled with mass spectrometry (RP-HPLC-MS)technique for the method development. Here, we have developed a novel multiple reaction monitoring method along with optimized parameters for quantification of EPA and DHA as ethyl esters. Additionally, we attempted to validate the bio-analytical method by conducting the sensitivity, selectivity, precision accuracy batch, carryover test and matrix stability experiments. Furthermore, we also implemented our validated method for evaluation of pharmacokinetics of omega fatty acid ethyl ester formulations. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Synthesis and structural elucidation of glutathione and N-aceyl-cysteine conjugates of 5-aminosalicylic acid

    DEFF Research Database (Denmark)

    Jensen, J.; Cornett, Claus; Olsen, C. E.

    1993-01-01

    The ability of 5-aminosalicylic acid (5-ASA) to be oxidized to a quinone monoimine compound capable of conjugating with nucleophilic compounds such as N-acetyl-cysteine (NAC) and glutathione (GSH) has been investigated in vitro. Three isomeric conjugates of 5-ASA and NAC as well as three isomeric...... conjugates of 5-ASA and GSH were found to be formed. 5-ASA was initially oxidized by PbO2 in a solution of TRIS-HCl buffer pH 9.3 followed by the in situ addition of N-acetyl-cysteine or glutathione to the oxidized 5-ASA at pH 7.5. The resulting conjugates were N-acetylated at the aromatic amino group...... to investigate whether such conjugates are excreted in the urine from persons treated with 5-ASA. The N-acetyl-cysteine conjugates could be detected by fluorescense, which resulted in low detection limits ranging from 0.02 mug to 0.06 mug per ml corresponding to the transformation of about 0.003% of the daily...

  11. Early dietary intervention with structured triacylglycerols containing docosahexaenoic acid. Effect on brain, liver, and adipose tissue lipids

    DEFF Research Database (Denmark)

    Christensen, Merete Myrup; Høy, Carl-Erik

    1997-01-01

    Newborn rats were fed liquid diets containing 7 wt% fat in which 3.8% of the total fatty acids were 22:6n-3. The fats were either a specificstructured oil with 22:6n-3 mostly located in the sn-2 position or a randomized oil with 22:6n-3 equally distributed in the triacylglycerol (TAG)molecules. T...

  12. Pharmacokinetic Profiling of Conjugated Therapeutic Oligonucleotides: A High-Throughput Method Based Upon Serial Blood Microsampling Coupled to Peptide Nucleic Acid Hybridization Assay.

    Science.gov (United States)

    Godinho, Bruno M D C; Gilbert, James W; Haraszti, Reka A; Coles, Andrew H; Biscans, Annabelle; Roux, Loic; Nikan, Mehran; Echeverria, Dimas; Hassler, Matthew; Khvorova, Anastasia

    2017-12-01

    Therapeutic oligonucleotides, such as small interfering RNAs (siRNAs), hold great promise for the treatment of incurable genetically defined disorders by targeting cognate toxic gene products for degradation. To achieve meaningful tissue distribution and efficacy in vivo, siRNAs must be conjugated or formulated. Clear understanding of the pharmacokinetic (PK)/pharmacodynamic behavior of these compounds is necessary to optimize and characterize the performance of therapeutic oligonucleotides in vivo. In this study, we describe a simple and reproducible methodology for the evaluation of in vivo blood/plasma PK profiles and tissue distribution of oligonucleotides. The method is based on serial blood microsampling from the saphenous vein, coupled to peptide nucleic acid hybridization assay for quantification of guide strands. Performed with minimal number of animals, this method allowed unequivocal detection and sensitive quantification without the need for amplification, or further modification of the oligonucleotides. Using this methodology, we compared plasma clearances and tissue distribution profiles of two different hydrophobically modified siRNAs (hsiRNAs). Notably, cholesterol-hsiRNA presented slow plasma clearances and mainly accumulated in the liver, whereas, phosphocholine-docosahexaenoic acid-hsiRNA was rapidly cleared from the plasma and preferably accumulated in the kidney. These data suggest that the PK/biodistribution profiles of modified hsiRNAs are determined by the chemical nature of the conjugate. Importantly, the method described in this study constitutes a simple platform to conduct pilot assessments of the basic clearance and tissue distribution profiles, which can be broadly applied for evaluation of new chemical variants of siRNAs and micro-RNAs.

  13. Effects of dietary conjugated linoleic acid (CLA), n-3 and n-6 fatty ...

    African Journals Online (AJOL)

    An experiment was conducted on broiler chickens to study the effects of conjugated linoleic acid (CLA), fish oil, soybean oil or their mixtures (at 7% for single and 3.5% + 3.5% for mixtures) as well as up 12% dosage of palm oil, on the performance and carcass traits of broiler chickens. The chicks fed 7% fish oil or 7% CLA ...

  14. Intestinal absorption and biliary secretion of ursodeoxycholic acid and its taurine conjugate

    NARCIS (Netherlands)

    Rudolph, G; Kloeters-Plachky, P; Sauer, P; Stiehl, A

    Background Ursodeoxycholic acid (UDCA) and its taurine conjugate (TUDCA) exert a protective effect in cholestatic liver diseases. A greater hepatoprotective effect of TUDCA has been suggested. Absorption appears to be a limiting factor and up to now has not been studied in man. Methods We studied

  15. The effect of long-term feeding of conjugated linoleic acid on fertility ...

    African Journals Online (AJOL)

    The objective of this study was to determine the effects of the long-term feeding of conjugated linoleic acid (CLA) on laying hen performance, egg fertility and hatchability of fertile eggs of Japanese quail (Coturnix coturnix japonica). One hundred and sixty 7-day old Japanese quail chicks were randomly assigned to four ...

  16. Effects of Bariatric Surgery on Serum Bile Acid Composition and Conjugation in a Diabetic Rat Model.

    Science.gov (United States)

    Wu, Qunzheng; Zhang, Xiang; Zhong, Mingwei; Han, Haifeng; Liu, Shaozhuang; Liu, Teng; Wei, Meng; Guo, Wei; Xie, Haibin; Hu, Sanyuan; Zhang, Guangyong

    2016-10-01

    Serum bile acids (BAs) are elevated following bariatric surgery and have emerged as a potential glucose-lowering beneficial factor. The change of BA components and its underlying mechanisms may be of great significance during bariatric surgery. The aim of this study is to investigate the effects of different bariatric procedures on serum BA composition and explore the potential mechanisms using a diabetic rat model. Duodenal-jejunal bypass (DJB), sleeve gastrectomy (SG), and sham operation were performed in diabetic rats induced by high-fat diet (HFD) and streptozotocin (STZ). Body weight, food intake, oral glucose tolerance test (OGTT), and insulin tolerance test (ITT) were measured at indicated time points. Serum BAs composition and the expression of cholesterol 7α hydroxylase (CYP7A1), bile acid: CoA synthase (BACS) and bile acid-CoA: amino acid N-acyltransferase (BAAT) at both transcriptional and protein levels in the liver were evaluated at 12 weeks postoperatively. Compared with sham group, DJB and SG both achieved rapid and sustained improvements in glucose tolerance and insulin sensitivity. They also resulted in increased serum BAs, especially the taurine-conjugated BAs by elevated conjugation. No obvious difference was detected between DJB and SG except that SG achieved decreased weight gain and food intake. The preferentially elevated serum taurine-conjugated BAs were similar after different bariatric surgeries, and the enhanced conjugation of BAs in the liver might account for the changed serum BAs profiles.

  17. Synthesis of highly stable folic acid conjugated magnetite nanoparticles for targeting cancer cells

    International Nuclear Information System (INIS)

    Mohapatra, S; Mallick, S K; Maiti, T K; Ghosh, S K; Pramanik, P

    2007-01-01

    A new approach towards the design of folic acid conjugated magnetic nanoparticles for enhancing their site specific intracellular uptake against a folate receptor overexpressing cancer cells is reported. Magnetite nanoparticles were prepared by coprecipitation from an Fe 3+ and Fe 2+ solution followed by surface modification with 2-carboxyethyl phosphonic acid to form carboxyl group terminated nanoparticles. Then folic acid and fluorescein isothiocyanate (FITC) were conjugated with carboxylic acid functionalized magnetite nanoparticles using 2,2'-(ethylenedioxy)-bis-ethylamine. These folate-conjugated nanoparticles were characterized in terms of their size by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Surface functional groups and surface composition were analyzed by Fourier transform infrared (FTIR) spectroscopy and x-ray photoelectron spectroscopy (XPS), respectively. Vibration sample magnetometry (VSM) measurements showed the superparamagnetic nature of the particles at room temperature. Folate-conjugated magnetic nanoparticles are noncytotoxic and receptor mediated internalization by HeLa and B16 melanoma F0 cancer cells was confirmed by flow cytometry and confocal microscopy

  18. Synthetic Nucleic Acid Analogues in Gene Therapy: An Update for Peptide–Oligonucleotide Conjugates

    DEFF Research Database (Denmark)

    Taskova, Maria; Mantsiou, Anna; Astakhova, Kira

    2017-01-01

    The main objective of this work is to provide an update on synthetic nucleic acid analogues and nanoassemblies as tools in gene therapy. In particular, the synthesis and properties of peptide–oligonucleotide conjugates (POCs), which have high potential in research and as therapeutics, are described...

  19. Dietary conjugated linoleic acid modify gene expression in liver, muscles, and fat tissues of finishing pigs

    DEFF Research Database (Denmark)

    Tous, Nuria; Theil, Peter Kappel; Lauridsen, Charlotte

    2012-01-01

    The aim of this study was to investigate underlying mechanisms of dietary conjugated linoleic acid (CLA) on lipid metabolism in various tissues of pigs. Sixteen gilts (73 ± 3 kg) were fed a control (containing sunflower oil) or an experimental diet in which 4% of sunflower oil was replaced by CLA...

  20. Dietary Docosahexaenoic Acid Improves Cognitive Function, Tissue Sparing, and Magnetic Resonance Imaging Indices of Edema and White Matter Injury in the Immature Rat after Traumatic Brain Injury.

    Science.gov (United States)

    Schober, Michelle E; Requena, Daniela F; Abdullah, Osama M; Casper, T Charles; Beachy, Joanna; Malleske, Daniel; Pauly, James R

    2016-02-15

    Traumatic brain injury (TBI) is the leading cause of acquired neurologic disability in children. Specific therapies to treat acute TBI are lacking. Cognitive impairment from TBI may be blunted by decreasing inflammation and oxidative damage after injury. Docosahexaenoic acid (DHA) decreases cognitive impairment, oxidative stress, and white matter injury in adult rats after TBI. Effects of DHA on cognitive outcome, oxidative stress, and white matter injury in the developing rat after experimental TBI are unknown. We hypothesized that DHA would decrease early inflammatory markers and oxidative stress, and improve cognitive, imaging and histologic outcomes in rat pups after controlled cortical impact (CCI). CCI or sham surgery was delivered to 17 d old male rat pups exposed to DHA or standard diet for the duration of the experiments. DHA was introduced into the dam diet the day before CCI to allow timely DHA delivery to the pre-weanling pups. Inflammatory cytokines and nitrates/nitrites were measured in the injured brains at post-injury Day (PID) 1 and PID2. Morris water maze (MWM) testing was performed at PID41-PID47. T2-weighted and diffusion tensor imaging studies were obtained at PID12 and PID28. Tissue sparing was calculated histologically at PID3 and PID50. DHA did not adversely affect rat survival or weight gain. DHA acutely decreased oxidative stress and increased anti-inflammatory interleukin 10 in CCI brains. DHA improved MWM performance and lesion volume late after injury. At PID12, DHA decreased T2-imaging measures of cerebral edema and decreased radial diffusivity, an index of white matter injury. DHA improved short- and long-term neurologic outcomes after CCI in the rat pup. Given its favorable safety profile, DHA is a promising candidate therapy for pediatric TBI. Further studies are needed to explore neuroprotective mechanisms of DHA after developmental TBI.

  1. Effects of early maternal docosahexaenoic acid intake on neuropsychological status and visual acuity at five years of age of breast-fed term infants.

    Science.gov (United States)

    Jensen, Craig L; Voigt, Robert G; Llorente, Antolin M; Peters, Sarika U; Prager, Thomas C; Zou, Yali L; Rozelle, Judith C; Turcich, Marie R; Fraley, J Kennard; Anderson, Robert E; Heird, William C

    2010-12-01

    We previously reported better psychomotor development at 30 months of age in infants whose mothers received a docosahexaenoic acid (DHA) (22:6n-3) supplement for the first 4 months of lactation. We now assess neuropsychological and visual function of the same children at 5 years of age. Breastfeeding women were assigned to receive identical capsules containing either a high-DHA algal oil (∼200 mg/d of DHA) or a vegetable oil (containing no DHA) from delivery until 4 months postpartum. Primary outcome variables at 5 years of age were measures of gross and fine motor function, perceptual/visual-motor function, attention, executive function, verbal skills, and visual function of the recipient children at 5 years of age. There were no differences in visual function as assessed by the Bailey-Lovie acuity chart, transient visual evoked potential or sweep visual evoked potential testing between children whose mothers received DHA versus placebo. Children whose mothers received DHA versus placebo performed significantly better on the Sustained Attention Subscale of the Leiter International Performance Scale (46.5 ± 8.9 vs 41.9 ± 9.3, P DHA supplementation versus placebo for the first 4 months of breastfeeding performed better on a test of sustained attention. This, along with the previously reported better performance of the children of DHA-supplemented mothers on a test of psychomotor development at 30 months of age, suggests that DHA intake during early infancy confers long-term benefits on specific aspects of neurodevelopment. Copyright © 2010 Mosby, Inc. All rights reserved.

  2. Effects of dietary supplementation with docosahexaenoic acid (DHA on hippocampal gene expression in streptozotocin induced diabetic C57Bl/6 mice

    Directory of Open Access Journals (Sweden)

    Jency Thomas

    2015-08-01

    Full Text Available A body of evidence has accumulated indicating diabetes is associated with cognitive impairments. Effective strategies are therefore needed that will delay or prevent the onset of these diabetes-related deficits. In this regard, dietary modification with the naturally occurring compound, docosahexaenoic acid (DHA, holds significant promise as it has been shown to have anti-inflammatory, anti-oxidant, and anti-apoptotic properties. The hippocampus, a limbic structure involved in cognitive functions such as memory formation, is particularly vulnerable to the neurotoxic effects related to diabetes, and we have previously shown that streptozotocin-induced diabetes alters hippocampal gene expression, including genes involved in synaptic plasticity and neurogenesis. In the present study, we explored the effects of dietary supplementation with DHA on hippocampal gene expression in C57Bl/6 diabetic mice. Diabetes was established using streptozotocin (STZ and once stable, the dietary intervention group received AIN93G diet supplemented with DHA (50 mg/kg/day for 6 weeks. Microarray based genome-wide expression analysis was carried out on the hippocampus of DHA supplemented diabetic mice and confirmed by real time polymerase chain reaction (RT-qPCR. Genome-wide analysis identified 353 differentially expressed genes compared to non-supplemented diabetic mice. For example, six weeks of dietary DHA supplementation resulted in increased hippocampal expression of Igf II and Sirt1 and decreased expression of Tnf-α, Il6, Mapkapk2 and ApoE, compared to non-supplemented diabetic mice. Overall, DHA supplementation appears to alter hippocampal gene expression in a way that is consistent with it being neuroprotective in the context of the metabolic and inflammatory insults associated with diabetes.

  3. Supplementing female rats with DHA-lysophosphatidylcholine increases docosahexaenoic acid and acetylcholine contents in the brain and improves the memory and learning capabilities of the pups

    Energy Technology Data Exchange (ETDEWEB)

    Valenzuela, A.; Nieto, S.; Sanhueza, J.; Morgado, N.; Rojas, I.; Zanartu, P.

    2010-07-01

    Docosahexaenoic acid (Dha) is supplied to the foetus and newborn through the mother from their own reserves and their diet. No consensus about the best form to supplement DHA has been established. We propose that DHA containing lysophosphatidylcholine (DHA-LPC), obtained from DHA-rich eggs may be a suitable form of DHA and choline (the precursor of acetylcholine) supplementation. We evaluated the effectiveness of DHA-LPC to increase DHA and acetylcholine concentration in the brain of pups born from female rats supplemented with DHA-LPC before and during pregnancy. We also evaluated the effect of DHA supplementation on learning and memory capabilities of pups through the Skinner test for operant conditioning. Female Wistar rats received 40-day supplementation of DHA-LPC (8 mg DHA/kg b.w/daily.), before and during pregnancy. After delivery, plasma, erythrocyte, liver, and adipose tissue DHA and plasma choline were analyzed. Brains from 60 day-old pups separated into frontal cortex, cerebellum, striatum, hippocampus, and occipital cortex, were assessed for DHA, acetylcholine, and acetylcholine transferase (CAT) activity. Pups were subjected to the Skinner box test. DHA-LPC supplementation produces higher choline and liver DHA contents in the mothers plasma and increases the pups DHA and acetylcholine in the cerebellum and hippocampus. CAT was not modified by supplementation. The Skinner test shows that pups born from DHA-LPC supplemented mothers exhibit better scores of learning and memory than the controls. Conclusion: DHA-LPC may be an adequate form for DHA supplementation during the perinatal period. (Author) 66 refs.

  4. Therapeutic Efficacy of Fenugreek Extract or/and Choline with Docosahexaenoic Acid in Attenuating Learning and Memory Deficits in Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    Anjaneyulu K

    2018-04-01

    Full Text Available Background: Studies have demonstrated that estradiol influences cognitive functions. Phytoestrogens and many other estrogen-like compounds in plants have beneficial effects on cognitive performance in postmenopausal women. However, there is no evident report of fenugreek and choline-Docosahexaenoic Acid (DHA on cognition in ovariectomized rats. Aim and Objectives: The present study was aimed to evaluate the therapeutic efficacy of fenugreek extract or/and choline- DHA in attenuating ovariectomy-induced memory impairment, brain antioxidant status and hippocampal neural cell deficits in the rat model. Material and Methods: Female Wistar 9-10 months old rats were grouped (n=12/group as - (1 Normal Control (NC, (2 Ovariectomized (OVX, (3 OVX+FG (hydroalcoholic seed extract of fenugreek, (4 OVX+C-DHA,(5 OVX+FG+C-DHA and (6 OVX+Estradiol. Groups 2- 6 were bilaterally OVX. FG, C-DHA was supplemented orally for 30 days, 14 days after ovariectomy. Assessment of learning and memory was performed by passive avoidance test. Oxidative stress and antioxidant markers were assessed by standard methods. Nissl stained hippocampal sections were analyzed to determine alterations in neural cell numbers in CA1, CA3 and dentate gyrus. Results: Supplementation of FG or/and choline with DHA to OVX rats, caused significant improvement in learning and memory as well as decreased neural cell deficits compared to the same in OVX rats. Further, significantly reduced levels of brain Malondialdehyde (MDA and increased levels of Glutathione (GSH were observed. Conclusion: Therapeutic supplementation of FG with choline-DHA significantly attenuates ovariectomy-induced neurocognitive deficits in rats.

  5. Preparation of chitosan-ferulic acid conjugate: Structure characterization and in the application of pharmaceuticals.

    Science.gov (United States)

    Li, Chen; Li, Jian-Bin

    2017-12-01

    A novel drug delivery system based on chitosan derivatives was prepared by introducting ferulic acid to chitosan adopting a free radical-induced grafting procedure. This paper used an ascorbic acid/hydrogen peroxide redox pair as radical initiator. The chitosan derivative was characterized by Fourier transformed infrared (FTIR), Ultraviolet-visible spectrum (UV), Differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Electron microscopic scanning (SEM). What is more, preparing microcapsules with the chitosan conjugate as wall material, the drug release propertie of chitosan conjugates were compared with that of a blank chitosan, which treated in the same conditions but in the absence of ferulic acid. The study clearly demonstrates that free radical-induced grafting procedure was an effective reaction methods and chitosan-ferulic acid is a potential functionalized carrier material for drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Nanomolar Cellular Antisense Activity of Peptide Nucleic Acid (PNA) Cholic Acid ("Umbrella") and Cholesterol Conjugates Delivered by Cationic Lipids

    DEFF Research Database (Denmark)

    Shiraishi, Takehiko; Nielsen, Peter E

    2012-01-01

    of cholesterol and cholic acid ("umbrella") derivatives of splice correction antisense PNA oligomers. While the conjugates alone were practically inactive up to 1 µM, their activity was dramatically improved when delivered by a cationic lipid transfection agent (LipofectAMINE2000). In particular, PNAs...

  7. Conjugated linolenic acid (CLnA), conjugated linoleic acid (CLA) and other biohydrogenation intermediates in plasma and milk fat of cows fed raw or extruded linseed.

    Science.gov (United States)

    Akraim, F; Nicot, M C; Juaneda, P; Enjalbert, F

    2007-07-01

    Thirty lactating dairy cows were used in a 3 × 3 Latin-square design to investigate the effects of a raw or extruded blend of linseed and wheat bran (70:30) on plasma and milk fatty-acids (FA). Linseed diets, containing 16.6% linseed blend on a dry-matter basis, decreased milk yield and protein percentage. They decreased the proportions of FA with less than 18 carbons in plasma and milk and resulted in cis-9, cis-12, cis-15 18:3 proportions that were more than three and four times higher in plasma and milk, respectively, whereas cis-9, cis-12 18:2 proportions were decreased by 10-15%. The cis-9, trans-11, cis-15 18:3 isomer of conjugated linolenic acid was not detected in the milk of control cows, but was over 0.15% of total FA in the milk fat of linseed-supplemented cows. Similarly, linseed increased plasma and milk proportions of all biohydrogenation (BH) intermediates in plasma and milk, including the main isomer of conjugated linoleic acid cis-9, trans-11 18:2, except trans-4 18:1 and cis-11, trans-15 18:2 in plasma lipids. In milk fat, compared with raw linseed, extruded linseed further reduced 6:0-16:0 even-chain FA, did not significantly affect the proportions of 18:0, cis-9 18:1 and cis-9, cis-12 18:2, tended to increase cis-9, cis-12, cis-15 18:3, and resulted in an additional increase in the proportions of most BH intermediates. It was concluded that linseed addition can improve the proportion of conjugated linoleic and linolenic acids, and that extrusion further increases the proportions of intermediates of ruminal BH in milk fat.

  8. Conjugated linoleic acids as functional food: an insight into their health benefits

    OpenAIRE

    Benjamin Sailas; Spener Friedrich

    2009-01-01

    Abstract This review evaluates the health benefits of the functional food, conjugated linoleic acids (CLA) - a heterogeneous group of positional and geometric isomers of linoleic acid predominantly found in milk, milk products, meat and meat products of ruminants. During the past couple of decades, hundreds of reports - principally based on in vitro, microbial, animal, and of late clinical trials on humans - have been accumulating with varying biological activities of CLA isomers. These studi...

  9. Dietary conjugated linoleic acids affect tissue lipid composition but not de novo lipogenesis in finishing pigs

    OpenAIRE

    Bee , Giuseppe

    2001-01-01

    International audience; Dietary conjugated linoleic acids (CLA) have been reported to profoundly affect lipid metabolism and to act as repartitioning agents. Currently, little is known about their effect on the fatty acid profile of tissue lipids in pigs. In the present study we determined the lipid composition of the backfat inner (BFI) and outer layer (BFO), omental fat (OF) and intramuscular fat (IMF) of the longissimus dorsi muscle in 24 Swiss Large White pigs fed diets supplemented eithe...

  10. Dietary choline and phospholipid supplementation enhanced docosahexaenoic acid enrichment in egg yolk of laying hens fed a 2% Schizochytrium powder-added diet.

    Science.gov (United States)

    Wang, H; Zhang, H J; Wang, X C; Wu, S G; Wang, J; Xu, L; Qi, G H

    2017-08-01

    The aim of this study was to evaluate the effect of dietary phospholipid supplementation on laying hen performance, egg quality, and the fatty acid profile of egg yolks from hens fed a 2% Schizochytrium powder diet. Three-hundred-sixty 28-wk-old Hy-line W-36 laying hens were randomly allocated to one of the 5 dietary treatments, each treatment with 6 replicates of 12 birds each. All diets included 2% Schizochytrium powder (docosahexaenoic acid [DHA], 137.09 mg/g). The control group was not supplemented with any additional phospholipids, whereas the other 4 experimental diets were supplemented with 1,000 mg/kg choline (CHO), 1,000 mg/kg monoethanolamine (MEA), 1,000 mg/kg lysophosphatidylcholine (LPC), or 500 mg/kg LPC + 500 mg/kg MEA (LPC + MEA). The experimental diets were isocaloric (metabolizable energy, 11.15 MJ/kg) and isonitrogenous (crude protein, 16.60%). The feeding trial lasted 28 days. Laying hen performance and egg quality were not affected (P > 0.05) by the diets used. The monounsaturated fatty acid (MUFA) level was reduced in the LPC group at d 28 (P egg yolks in the LPC group had a trend to increase in comparison to the control (P = 0.07). The CHO and LPC groups had higher omega-3 (n-3) PUFA and DHA levels and lower n-6/n-3 ratios than the other groups at d 28 (P egg yolk reached a plateau after the laying hens consumed the experimental diets for 14 days, and higher yolk DHA contents were observed in the CHO and LPC groups as compared with the other groups at d 14. It was concluded that dietary choline supplementation for more than 14 d enhanced egg yolk enrichment with n-3 PUFA and DHA when laying hen diets were supplemented with 2% Schizochytrium powder. All the diets had no adverse effect on hen performance, egg quality, or egg components under the experimental condition. © 2017 Poultry Science Association Inc.

  11. Effect of Oral Docosahexaenoic Acid (DHA) Supplementation on DHA Levels and Omega-3 Index in Red Blood Cell Membranes of Breast Cancer Patients.

    Science.gov (United States)

    Molfino, Alessio; Amabile, Maria I; Mazzucco, Sara; Biolo, Gianni; Farcomeni, Alessio; Ramaccini, Cesarina; Antonaroli, Simonetta; Monti, Massimo; Muscaritoli, Maurizio

    2017-01-01

    Rationale: Docosahexaenoic acid (DHA) in cell membrane may influence breast cancer (BC) patients' prognosis, affecting tumor cells sensitivity to chemo- and radio-therapy and likely modulating inflammation. The possibility of identifying BC patients presenting with low DHA levels and/or low ability of DHA incorporation into cell membrane might help to treat this condition. Methods: We enrolled BC patients and healthy controls, recording their seafood dietary intake. DHA in form of algal oil was administered for 10 consecutive days (2 g/day). Blood samples were collected at baseline (T0) and after 10 days of supplementation (T1) to assess DHA, omega-3 index, as the sum of DHA + eicosapentaenoic acid (EPA), in red blood cells (RBC) membranes and plasma tumor necrosis factor-alpha and interleukin-6 levels. Pre- and post-treatment fatty acid profiles were obtained by gas-chromatography. Parametric and non-parametric tests were performed, as appropriate, and P -value DHA and omega-3 index increased from T0 to T1 in the 3 groups of BC patients and in controls ( P DHA incorporation between each group of BC patients and between patients and controls, except for M group, which incorporated higher DHA levels with respect to controls (β = 0.42; P = 0.03). No association was documented between cytokines levels and DHA and omega-3 index at baseline and after DHA supplementation. Independent of the presence of BC, women considered as "good seafood consumers" showed at baseline DHA and omega-3 index higher with respect to "low seafood consumers" ( P = 0.04; P = 0.007, respectively). After supplementation, the increase in DHA levels was greater in "low seafood consumers" with respect to "good seafood consumers" ( P DHA supplementation was associated with increased DHA levels and omega-3 index in RBC membranes of BC cancer patients, independent of the type of BC presentation, and in controls. BRCA1/2 mutation, as well as low seafood consuming habits in both BC patients and healthy

  12. Effect of Oral Docosahexaenoic Acid (DHA Supplementation on DHA Levels and Omega-3 Index in Red Blood Cell Membranes of Breast Cancer Patients

    Directory of Open Access Journals (Sweden)

    Alessio Molfino

    2017-07-01

    Full Text Available Rationale: Docosahexaenoic acid (DHA in cell membrane may influence breast cancer (BC patients' prognosis, affecting tumor cells sensitivity to chemo- and radio-therapy and likely modulating inflammation. The possibility of identifying BC patients presenting with low DHA levels and/or low ability of DHA incorporation into cell membrane might help to treat this condition.Methods: We enrolled BC patients and healthy controls, recording their seafood dietary intake. DHA in form of algal oil was administered for 10 consecutive days (2 g/day. Blood samples were collected at baseline (T0 and after 10 days of supplementation (T1 to assess DHA, omega-3 index, as the sum of DHA + eicosapentaenoic acid (EPA, in red blood cells (RBC membranes and plasma tumor necrosis factor-alpha and interleukin-6 levels. Pre- and post-treatment fatty acid profiles were obtained by gas-chromatography. Parametric and non-parametric tests were performed, as appropriate, and P-value < 0.05 was considered statistically significant.Results: Forty-three women were studied, divided into 4 groups: 11 patients with BRCA1/2 gene mutation (M group, 12 patients with familiar positive history for BC (F group, 10 patients with sporadic BC (S group, and 10 healthy controls (C group. DHA and omega-3 index increased from T0 to T1 in the 3 groups of BC patients and in controls (P < 0.001. No difference was found in DHA incorporation between each group of BC patients and between patients and controls, except for M group, which incorporated higher DHA levels with respect to controls (β = 0.42; P = 0.03. No association was documented between cytokines levels and DHA and omega-3 index at baseline and after DHA supplementation. Independent of the presence of BC, women considered as “good seafood consumers” showed at baseline DHA and omega-3 index higher with respect to “low seafood consumers” (P = 0.04; P = 0.007, respectively. After supplementation, the increase in DHA levels was

  13. Incorporation of eicosapentaenioic and docosahexaenoic acids into breast adipose tissue of women at high risk of breast cancer: a randomized clinical trial of dietary fish and n-3 fatty acid capsules.

    Science.gov (United States)

    Straka, Shana; Lester, Joanne L; Cole, Rachel M; Andridge, Rebecca R; Puchala, Sarah; Rose, Angela M; Clinton, Steven K; Belury, Martha A; Yee, Lisa D

    2015-09-01

    The fatty acid profile of dietary lipids is reflected in mammary adipose tissue and may influence mammary gland biology and cancer risk. To determine the effects of fish consumption on breast adipose tissue fatty acids, we conducted a study of fish versus n-3 PUFA supplements in women at increased risk of breast cancer. High risk women were randomized to comparable doses of marine n-3 PUFAs as canned salmon + albacore or capsules for 3 months. Pre- and posttreatment fatty acid profiles were obtained by GC. Dietary fish (n = 12) and n-3 PUFA capsules (n = 13) yielded increased eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in plasma (p breast fat (p Women taking capsules had higher plasma and erythrocyte membrane EPA changes (∼four versus twofold, p = 0.002), without significant differences in DHA. Increases in breast adipose EPA, DHA were similar for both groups. Higher BMI correlated with smaller changes in plasma, erythrocyte membrane EPA, and breast adipose EPA, DHA. Adherence was excellent at 93.9% overall and higher in the fish arm (p = 0.01). Fish provides an excellent source of n-3 PUFAs that increases breast adipose EPA, DHA similar to supplements and represents a well-tolerated intervention for future studies of the impact of n-3 PUFAs and dietary patterns on breast cancer. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. An updated review of worldwide levels of docosahexaenoic and arachidonic acid in human breast milk by region.

    Science.gov (United States)

    Fu, Yuanqing; Liu, Xin; Zhou, Bing; Jiang, Alice C; Chai, Lingying

    2016-10-01

    We aimed to evaluate the DHA and arachidonic acid (AA) levels in human breast milk worldwide by country, region and socio-economic status. Descriptive review conducted on English publications reporting breast-milk DHA and AA levels. We systematically searched and identified eligible literature in PubMed from January 1980 to July 2015. Data on breast-milk DHA and AA levels from women who had given birth to term infants were included. Seventy-eight studies from forty-one countries were included with 4163 breast-milk samples of 3746 individuals. Worldwide mean levels of DHA and AA in breast milk were 0·37 (sd 0·11) % and 0·55 (sd 0·14) % of total fatty acids, respectively. The breast-milk DHA levels from women with accessibility to marine foods were significantly higher than those from women without accessibility (0·35 (sd 0·20) % v. 0·25 (sd 0·14) %, Pworldwide variation in breast-milk DHA and AA levels and underlines the need for future population- or region-specific investigations.

  15. The free fractions of circulating docosahexaenoic acid and eicosapentenoic acid as optimal end-point of measure in bioavailability studies on n-3 fatty acids.

    Science.gov (United States)

    Scarsi, Claudia; Levesque, Ann; Lisi, Lucia; Navarra, Pierluigi

    2015-05-01

    The high complexity of n-3 fatty acids absorption process, along with the huge amount of endogenous fraction, makes bioavailability studies with these agents very challenging and deserving special consideration. In this paper we report the results of a bioequivalence study between a new formulation of EPA+DHA ethyl esters developed by IBSA Institut Biochimique and reference medicinal product present on the Italian market. Bioequivalence was demonstrated according to the criteria established by the EMA Guideline on the Investigation of Bioequivalence. We found that the free fractions represent a better and more sensitive end-point for bioequivalence investigations on n-3 fatty acids, since: (i) the overall and intra-subject variability of PK parameters was markedly lower compared to the same variability calculated on the total DHA and EPA fractions; (ii) the absorption process was completed within 4h, and the whole PK profile could be drawn within 12-15 h from drug administration. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Docosahexaenoic acid status at 9 months is inversely associated with communicative skills in 3-year-old girls

    DEFF Research Database (Denmark)

    Engel, Sara; Tronhjem, Kathrine Marie Hagerup; Hellgren, Lars

    2013-01-01

    by the parents using third edition of the Ages and Stages Questionnaire (ASQ-3). RBC DHA levels ranged from 2.2% to 12.6% of the RBC fatty acids. The age of reaching milestones correlated with psychomotor development, particularly with gross motor function at 3 years. An association between milestones and later...... personal and social skills was also observed, but only for girls. In girls, RBC-DHA was found to be inversely correlated with communication at 3 years of age (odds ratio = 0.69, 95% confidence interval: 0.56-0.86, P = 0.001), but no other associations with psychomotor development or milestones were found....... The results from study indicate that DHA status at 9 months may not have a pronounced beneficial effect on psychomotor development in early childhood and that communicative skills at 3 years of age may even be inversely associated with early RBC-DHA levels in girls....

  17. Hybrid striped bass feeds based on fish oil, beef tallow, and eicosapentaenoic acid/docosahexaenoic acid supplements: Insight regarding fish oil sparing and demand for -3 long-chain polyunsaturated fatty acids.

    Science.gov (United States)

    Bowzer, J; Jackson, C; Trushenski, J

    2016-03-01

    Previous research suggests that saturated (SFA) and monounsaturated fatty acid (MUFA) rich lipids, including beef tallow, can make utilization or diet-to-tissue transfer of long-chain polyunsaturated fatty acids (LC-PUFA) more efficient. We hypothesized that using beef tallow as an alternative to fish oil may effectively reduce the LC-PUFA demand of hybrid striped bass × and allow for greater fish oil sparing. Accordingly, we evaluated growth performance and tissue fatty acid profiles of juvenile fish (23.7 ± 0.3 g) fed diets containing menhaden fish oil (considered an ideal source of LC-PUFA for this taxon), beef tallow (BEEF ONLY), or beef tallow amended with purified sources of eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA) to achieve levels corresponding to 50 or 100% of those observed in the FISH ONLY feed. Diets were randomly assigned to quadruplicate tanks of fish ( = 4; 10 fish/tank), and fish were fed assigned diets to apparent satiation once daily for 10 wk. Survival (98-100%) was equivalent among treatments, but weight gain (117-180%), specific growth rate (1.1-1.5% BW/d), feed intake (1.4-1.8% BW/d), thermal growth coefficient (0.50-0.70), and feed conversion ratio (FCR; 1.1-1.4, DM basis) varied. Except for FCR, no differences were observed between the FISH ONLY and BEEF ONLY treatments, but performance was generally numerically superior among fish fed the diets containing beef tallow supplemented with DHA at the 100% or both EPA and DHA at the 50% or 100% level. Tissue fatty acid composition was significantly distorted in favor among fish fed the beef tallow-based feeds; however, profile distortion was most overt in peripheral tissues. Results suggest that beef tallow may be used as a primary lipid source in practical diets for hybrid striped bass, but performance may be improved by supplementation with LC-PUFA, particularly DHA. Furthermore, our results suggest that -3 LC-PUFA requirements reported for hybrid striped bass may not be

  18. Cellular delivery and antisense effects of peptide nucleic acid conjugated to polyethyleneimine via disulfide linkers

    DEFF Research Database (Denmark)

    Berthold, Peter R; Shiraishi, Takehiko; Nielsen, Peter E

    2010-01-01

    Peptide nucleic acid (PNA) is potentially an attractive antisense and antigene agent for which more efficient cellular delivery systems are still warranted. The cationic polymer polyethylenimine (PEI) is commonly used for cellular transfection of DNA and RNA complexes, but is not readily applicable...... moiety) and further reacted this with a cysteine PNA. The level of modification was determined spectrophotometrically with high accuracy, and the PNA transfection efficiency of the conjugates was evaluated in an antisense luciferase splice-correction assay using HeLa pLuc705 cells. We find that PEI...... is an efficient vector for PNA delivery yielding significantly higher (up to 10-fold) antisense activity than an analogous PNA-octaarginine conjugate, even in the presence of chloroquine, which only slightly enhances the PEI-PNA activity. The PEI-PEG conjugates are preferred due to lower acute cellular toxicity...

  19. Intravenous infusion of docosahexaenoic acid increases serum concentrations in a dose-dependent manner and increases seizure latency in the maximal PTZ model.

    Science.gov (United States)

    Trépanier, Marc-Olivier; Kwong, Kei-Man; Domenichiello, Anthony F; Chen, Chuck T; Bazinet, Richard P; Burnham, W M

    2015-09-01

    Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid (n-3 PUFA) that has been shown to raise seizure thresholds in the maximal pentylenetetrazole model following acute subcutaneous (s.c.) administration in rats. Following s.c. administration, however, the dose-response relationship for DHA has shown an inverted U-pattern. The purposes of the present experiment were as follows: (1) to determine the pattern of serum unesterified concentrations resulting from the intravenous (i.v.) infusions of various doses of DHA, (2) to determine the time course of these concentrations following the discontinuation of the infusions, and (3) to determine whether seizure protection in the maximal PTZ model would correlate with serum unesterified DHA levels. Animals received 5-minute i.v. infusions of saline or 25, 50, 100, or 200mg/kg of DHA via a cannula inserted into one of the tail veins. Blood was collected during and after the infusions by means of a second cannula inserted into the other tail vein (Experiment 1). A separate group of animals received saline or 12.5-, 25-, 50-, 100-, or 200 mg/kg DHA i.v. via a cannula inserted into one of the tail veins and were then seizure-tested in the maximal PTZ model either during infusion or after the discontinuation of the infusions. Slow infusions of DHA increased serum unesterified DHA concentrations in a dose-dependent manner, with the 200-mg/kg dose increasing the concentration approximately 260-fold compared with saline-infused animals. Following discontinuation of the infusions, serum concentrations rapidly dropped toward baseline, with half-lives of approximately 40 and 11s for the 25-mg/kg dose and 100-mg/kg dose, respectively. In the seizure-tested animals, DHA significantly increased latency to seizure onset in a dose-dependent manner. Following the discontinuation of infusion, seizure latency rapidly decreased toward baseline. Overall, our study suggests that i.v. infusion of unesterified DHA results in

  20. Novel two-step synthesis of gold nanoparticles capped with bile acid conjugates

    International Nuclear Information System (INIS)

    Noponen, Virpi; Bhat, Shreedhar; Sievaenen, Elina; Kolehmainen, Erkki

    2008-01-01

    Bile acids and their conjugates are physiologically important molecules. Syntheses and structure elucidation combined with investigation of properties and applications of bile acids and their derivatives are of academic interest. The concept of using bile acids and their conjugates in nanoscience is a novel idea, which opens up fascinating prospects. In this article, an easy and simple route for obtaining N-lithocholyl-L-(cysteine ethyl ester) (3), capable of effectively capping and stabilizing metal nanoparticles, is described. The whole synthetic route needs only two steps giving a moderate to good yield. The gold NPs are characterized by elemental analysis, UV spectroscopy, and TEM. Additionally, 13 C CP/MAS NMR studies for different ligand/Au ratios have been performed

  1. 14S,21R-dihydroxy-docosahexaenoic acid treatment enhances mesenchymal stem cell amelioration of renal ischemia/reperfusion injury.

    Science.gov (United States)

    Tian, Haibin; Lu, Yan; Shah, Shraddha P; Wang, Quansheng; Hong, Song

    2012-05-01

    Bone marrow mesenchymal stem cells (MSCs) have shown potential to improve treatment of renal failure. The prohealing functions of MSCs have been found to be enhanced by treatment with the lipid mediator, 14S,21R-dihydroxy-docosa4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid (14S,21R-diHDHA). In this article, using a murine model of renal ischemia/reperfusion (I/R) injury, we found that treatment with 14S,21R-diHDHA enhanced MSC amelioration of renal I/R injury. Treated MSCs more efficiently inhibited I/R-induced elevation of serum creatinine levels, reduced renal tubular cell death, and inhibited infiltration of neutrophils, macrophages, and dendritic cells in kidneys. Conditioned medium from treated MSCs reduced the generation of tumor necrosis factor-α and reactive oxygen species by macrophages under I/R conditions. Infusion of treated MSCs more efficiently reduced I/R-damage to renal histological structures compared with untreated MSCs (injury score: 7.9±0.4 vs. 10.5±0.5). Treated MSCs were resistant to apoptosis in vivo when transplanted under capsules of I/R-injured kidneys (active caspase-3+ MSCs: 4.2%±2.8% vs. 11.7%±2.4% of control) and in vitro when cultured under I/R conditions. Treatment with 14S,21R-diHDHA promoted viability of MSCs through a mechanism involving activation of the phosphoinositide 3-kinase -Akt signaling pathway. Additionally, treatment of MSCs with 14S,21R-diHDHA promoted secretion of renotrophic hepatocyte growth factor and insulin growth factor-1. Similar results were obtained when 14S,21RdiHDHA was used to inhibit apoptosis of human MSCs (hMSCs) and to increase the generation of renotrophic cytokines from hMSCs. These findings provide a lead for new strategies in the treatment of acute kidney injury with MSCs.

  2. Thiolated polymers--thiomers: development and in vitro evaluation of chitosan-thioglycolic acid conjugates.

    Science.gov (United States)

    Kast, C E; Bernkop-Schnürch, A

    2001-09-01

    The aim of this study was to improve mucoadhesive properties of chitosan by the covalent attachment of thiol moieties to this cationic polymer. Mediated by a carbodiimide, thioglycolic acid (TGA) was covalently attached to chitosan. This was achieved by the formation of amide bonds between the primary amino groups of the polymer and the carboxylic acid group of TGA. Dependent on the pH-value and the weight ratio of polymer to TGA during the coupling reaction the resulting thiolated polymers, the so-called thiomers, displayed 6.58, 9.88, 27.44, and 38.23 micromole thiol groups per gram polymer. Tensile studies carried out with these chitosan-TGA conjugates on freshly excised porcine intestinal mucosa demonstrated a 6.3-, 8.6-, 8.9-, and 10.3-fold increase in the total work of adhesion (TWA) compared to the unmodified polymer, respectively. In contrast, the combination of chitosan and free unconjugated TGA showed almost no mucoadhesion. These data were in good correlation with further results obtained by another mucoadhesion test demonstrating a prolonged residence time of thiolated chitosan on porcine mucosa. The swelling behavior of all conjugates was thereby exactly in the same range as for an unmodified polymer pretreated in the same way. Furthermore, it could be shown that chitosan-TGA conjugates are still biodegradable by the glycosidase lysozyme. According to these results. chitosan-TGA conjugates represent a promising tool for the development of mucoadhesive drug delivery systems.

  3. Preliminary Validation of a High Docosahexaenoic Acid (DHA and -Linolenic Acid (ALA Dietary Oil Blend: Tissue Fatty Acid Composition and Liver Proteome Response in Atlantic Salmon (Salmo salar Smolts.

    Directory of Open Access Journals (Sweden)

    Waldo G Nuez-Ortín

    Full Text Available Marine oils are important to human nutrition as the major source of docosahexaenoic acid (DHA, a key omega-3 long-chain (≥C20 polyunsaturated fatty acid (n-3 LC-PUFA that is low or lacking in terrestrial plant or animal oils. The inclusion of fish oil as main source of n-3 LC-PUFA in aquafeeds is mostly limited by the increasing price and decreasing availability. Fish oil replacement with cheaper terrestrial plant and animal oils has considerably reduced the content of n-3 LC-PUFA in flesh of farmed Atlantic salmon. Novel DHA-enriched oils with high alpha-linolenic acid (ALA content will be available from transgenic oilseeds plants in the near future as an alternative for dietary fish oil replacement in aquafeeds. As a preliminary validation, we formulated an oil blend (TOFX with high DHA and ALA content using tuna oil (TO high in DHA and the flaxseed oil (FX high in ALA, and assessed its ability to achieve fish oil-like n-3 LC-PUFA tissue composition in Atlantic salmon smolts. We applied proteomics as an exploratory approach to understand the effects of nutritional changes on the fish liver. Comparisons were made between fish fed a fish oil-based diet (FO and a commercial-like oil blend diet (fish oil + poultry oil, FOPO over 89 days. Growth and feed efficiency ratio were lower on the TOFX diet. Fish muscle concentration of n-3 LC-PUFA was significantly higher for TOFX than for FOPO fish, but not higher than for FO fish, while retention efficiency of n-3 LC-PUFA was promoted by TOFX relative to FO. Proteomics analysis revealed an oxidative stress response indicative of the main adaptive physiological mechanism in TOFX fish. While specific dietary fatty acid concentrations and balances and antioxidant supplementation may need further attention, the use of an oil with a high content of DHA and ALA can enhance tissue deposition of n-3 LC-PUFA in relation to a commercially used oil blend.

  4. Preliminary Validation of a High Docosahexaenoic Acid (DHA) and -Linolenic Acid (ALA) Dietary Oil Blend: Tissue Fatty Acid Composition and Liver Proteome Response in Atlantic Salmon (Salmo salar) Smolts.

    Science.gov (United States)

    Nuez-Ortín, Waldo G; Carter, Chris G; Wilson, Richard; Cooke, Ira; Nichols, Peter D

    2016-01-01

    Marine oils are important to human nutrition as the major source of docosahexaenoic acid (DHA), a key omega-3 long-chain (≥C20) polyunsaturated fatty acid (n-3 LC-PUFA) that is low or lacking in terrestrial plant or animal oils. The inclusion of fish oil as main source of n-3 LC-PUFA in aquafeeds is mostly limited by the increasing price and decreasing availability. Fish oil replacement with cheaper terrestrial plant and animal oils has considerably reduced the content of n-3 LC-PUFA in flesh of farmed Atlantic salmon. Novel DHA-enriched oils with high alpha-linolenic acid (ALA) content will be available from transgenic oilseeds plants in the near future as an alternative for dietary fish oil replacement in aquafeeds. As a preliminary validation, we formulated an oil blend (TOFX) with high DHA and ALA content using tuna oil (TO) high in DHA and the flaxseed oil (FX) high in ALA, and assessed its ability to achieve fish oil-like n-3 LC-PUFA tissue composition in Atlantic salmon smolts. We applied proteomics as an exploratory approach to understand the effects of nutritional changes on the fish liver. Comparisons were made between fish fed a fish oil-based diet (FO) and a commercial-like oil blend diet (fish oil + poultry oil, FOPO) over 89 days. Growth and feed efficiency ratio were lower on the TOFX diet. Fish muscle concentration of n-3 LC-PUFA was significantly higher for TOFX than for FOPO fish, but not higher than for FO fish, while retention efficiency of n-3 LC-PUFA was promoted by TOFX relative to FO. Proteomics analysis revealed an oxidative stress response indicative of the main adaptive physiological mechanism in TOFX fish. While specific dietary fatty acid concentrations and balances and antioxidant supplementation may need further attention, the use of an oil with a high content of DHA and ALA can enhance tissue deposition of n-3 LC-PUFA in relation to a commercially used oil blend.

  5. A synergistic antiproliferation effect of curcumin and docosahexaenoic acid in SK-BR-3 breast cancer cells: unique signaling not explained by the effects of either compound alone

    International Nuclear Information System (INIS)

    Altenburg, Jeffrey D; Bieberich, Andrew A; Terry, Colin; Harvey, Kevin A; VanHorn, Justin F; Xu, Zhidong; Jo Davisson, V; Siddiqui, Rafat A

    2011-01-01

    Breast cancer is a collection of diseases in which molecular phenotypes can act as both indicators and mediators of therapeutic strategy. Therefore, candidate therapeutics must be assessed in the context of multiple cell lines with known molecular phenotypes. Docosahexaenoic acid (DHA) and curcumin (CCM) are dietary compounds known to antagonize breast cancer cell proliferation. We report that these compounds in combination exert a variable antiproliferative effect across multiple breast cell lines, which is synergistic in SK-BR-3 cells and triggers cell signaling events not predicted by the activity of either compound alone. Dose response curves for CCM and DHA were generated for five breast cell lines. Effects of the DHA+ CCM combination on cell proliferation were evaluated using varying concentrations, at a fixed ratio, of CCM and DHA based on their individual ED 50 . Detection of synergy was performed using nonlinear regression of a sigmoid dose response model and Combination Index approaches. Cell molecular network responses were investigated through whole genome microarray analysis of transcript level changes. Gene expression results were validated by RT-PCR, and western blot analysis was performed for potential signaling mediators. Cellular curcumin uptake, with and without DHA, was analyzed via flow cytometry and HPLC. CCM+DHA had an antiproliferative effect in SK-BR-3, MDA-MB-231, MDA-MB-361, MCF7 and MCF10AT cells. The effect was synergistic for SK-BR-3 (ER - PR - Her2 + ) relative to the two compounds individually. A whole genome microarray approach was used to investigate changes in gene expression for the synergistic effects of CCM+DHA in SK-BR-3 cells lines. CCM+DHA triggered transcript-level responses, in disease-relevant functional categories, that were largely non-overlapping with changes caused by CCM or DHA individually. Genes involved in cell cycle arrest, apoptosis, inhibition of metastasis, and cell adhesion were upregulated, whereas genes

  6. In vivo PET imaging of the neuroinflammatory response in rat spinal cord injury using the TSPO tracer [18F]GE-180 and effect of docosahexaenoic acid

    International Nuclear Information System (INIS)

    Tremoleda, J.L.; Thau-Zuchman, O.; Davies, M.; Vadivelu, K.C.; Yip, P.K.; Michael-Titus, A.T.; Foster, J.; Sosabowski, J.; Khan, I.; Trigg, W.

    2016-01-01

    Traumatic spinal cord injury (SCI) is a devastating condition which affects millions of people worldwide causing major disability and substantial socioeconomic burden. There are currently no effective treatments. Modulating the neuroinflammatory (NI) response after SCI has evolved as a major therapeutic strategy. PET can be used to detect the upregulation of the 18-kDa translocator protein (TSPO), a hallmark of activated microglia in the CNS. We investigated whether PET imaging using the novel TSPO tracer [ 18 F]GE-180 can be used as a clinically relevant biomarker for NI in a contusion SCI rat model, and we present data on the modulation of NI by the lipid docosahexaenoic acid (DHA). A total of 22 adult male Wistar rats were subjected to controlled spinal cord contusion at the T10 spinal cord level. Six non-injured and ten T10 laminectomy only (LAM) animals were used as controls. A subset of six SCI animals were treated with a single intravenous dose of 250 nmol/kg DHA (SCI-DHA group) 30 min after injury; a saline-injected group of six animals was used as an injection control. PET and CT imaging was carried out 7 days after injury using the [ 18 F]GE-180 radiotracer. After imaging, the animals were killed and the spinal cord dissected out for biodistribution and autoradiography studies. In vivo data were correlated with ex vivo immunohistochemistry for TSPO. In vivo dynamic PET imaging revealed an increase in tracer uptake in the spinal cord of the SCI animals compared with the non-injured and LAM animals from 35 min after injection (P < 0.0001; SCI vs. LAM vs. non-injured). Biodistribution and autoradiography studies confirmed the high affinity and specific [ 18 F]GE-180 binding in the injured spinal cord compared with the binding in the control groups. Furthermore, they also showed decreased tracer uptake in the T10 SCI area in relation to the non-injured remainder of the spinal cord in the SCI-DHA group compared with the SCI-saline group (P < 0.05), supporting

  7. Preparation, isolation and identification of non-conjugated C18:2 fatty acid isomers.

    Science.gov (United States)

    Fardin-Kia, Ali Reza

    2016-12-01

    Non-conjugated geometric/positional isomers of linoleic acid (c9,c12-18:2) are often present in processed foods and oils. The following work presents a simple addition/elimination reaction for preparation of non-conjugated 18:2 fatty acid isomers. A mixture containing positional and geometric isomers of C18:2 fatty acids was produced by addition of hydrobromic acid to the fatty acid double bonds, followed by its elimination with a strong sterically hindered base. Pure 8,12-, 8,13-, 9,12-, and 9,13-18:2 fatty acid methyl esters were isolated from the synthetic mixture by a combination of sub-ambient RP-HPLC and Ag + -HPLC. The determination of the double bond position was achieved by GC-MS using picolinyl esters derivatives. The determination of the fatty acid double bond geometric configuration was obtained by partial hydrogenation of the isolated isomer with hydrazine, followed by the GC-FID analysis. Published by Elsevier Ireland Ltd.

  8. Diethylenetriaminepentaacetic acid-gadolinium (DTPA-Gd)-conjugated polysuccinimide derivatives as magnetic resonance imaging contrast agents.

    Science.gov (United States)

    Lee, Ha Young; Jee, Hye Won; Seo, Sung Mi; Kwak, Byung Kook; Khang, Gilson; Cho, Sun Hang

    2006-01-01

    Biocompatible polysuccinimide (PSI) derivatives conjugated with diethylenetriaminepentaacetic acid gadolinium (DTPA-Gd) were prepared as magnetic resonance imaging (MRI) contrast agents. In this study, we synthesized PSI derivatives incorporating methoxy-poly(ethylene glycol) (mPEG) as hydrophilic ligand, hexadecylamine as hydrophobic ligand, and DTPA-Gd as contrast agent. PSI was synthesized by the polycondensation polymerization of aspartic acid. All the synthesized materials were characterized by proton nuclear magnetic resonance (1H NMR). Critical micellization concentrations were determined using fluorescent probes (pyrene). Micelle size and shape were measured by electro-photometer light scattering (ELS) and atomic force microscopy (AFM). The formed micelle size ranged from 100 to 300 nm. The T1-weighted MR images of the phantom prepared with PSI-mPEG-C16-(DTPA-Gd) were obtained in a 3.0 T clinical MR imager, and the conjugates showed a great potential as MRI contrast agents.

  9. Synthesis and characterization of covalent diphenylalanine nanotube-folic acid conjugates

    DEFF Research Database (Denmark)

    León, John Jairo Castillo; Rindzevicius, Tomas; Wu, Kaiyu

    2014-01-01

    Herein, we describe the synthesis and characterization of a covalent nanoscale assembly formed between diphenylalanine micro/nanotubes (PNT) and folic acid (FA). The conjugate was obtained via chemical functionalization through coupling of amine groups of PNTs and carboxylic groups of FA. The sur...... for applications in the detection and diagnosis of cancer or tropical diseases such as leishmaniasis and as a carrier nanosystem delivering drugs to malignant tumors that overexpress folate receptors....

  10. Conjugated linoleic acid supplementation caused reduction of perilipin1 and aberrant lipolysis in epididymal adipose tissue

    International Nuclear Information System (INIS)

    Cai, Demin; Li, Hongji; Zhou, Bo; Han, Liqiang; Zhang, Xiaomei; Yang, Guoyu; Yang, Guoqing

    2012-01-01

    Highlights: ► Conjugated linoleic acid supplementation suppresses perilipin1 in epididymal fat. ► Conjugated linoleic acid inhibits promoter activity of perilipin1 in 3T3-L1 cells. ► Conjugated linoleic acids elevate basal but blunt hormone-stimulated lipolysis. -- Abstract: Perilipin1, a coat protein of lipid droplet, plays a key role in adipocyte lipolysis and fat formation of adipose tissues. However, it is not clear how the expression of perilipin1 is affected in the decreased white adipose tissues (WAT) of mice treated with dietary supplement of conjugated linoleic acids (CLA). Here we obtained lipodystrophic mice by dietary administration of CLA which exhibited reduced epididymal (EPI) WAT, aberrant adipocytes and decreased expression of leptin in this tissue. We found both transcription and translation of perilipin1 was suppressed significantly in EPI WAT of CLA-treated mice compared to that of control mice. The gene expression of negative regulator tumor necrosis factor α (TNFα) and the positive regulator Peroxisome Proliferator-Activated Receptor-γ (PPARγ) of perilipin1 was up-regulated and down-regulated, respectively. In cultured 3T3-L1 cells the promoter activity of perilipin1 was dramatically inhibited in the presence of CLA. Using ex vivo experiment we found that the basal lipolysis was elevated but the hormone-stimulated lipolysis blunted in adipose explants of CLA-treated mice compared to that of control mice, suggesting that the reduction of perilipin1 in white adipose tissues may at least in part contribute to CLA-mediated alternation of lipolysis of WAT.

  11. THE IMPACT OF CONJUGATED LINOLEIC ACID ADDITION ON PH VALUE OF LONGISSIMUS DORSI MUSCLE

    Directory of Open Access Journals (Sweden)

    Przemysław WASILEWSKI

    2009-08-01

    Full Text Available The subject of research was 60 crossbred gilts, divided into 6 groups, fed the fodder with addition of conjugated linoleic acid (CLA or sunflower oil (SFO in amount: 0.5; 1.0; and 2.0 %, respectively. Animals were slaughtered with the body weight ca. 95 kg. The aim of research was to determine pH value of loin meat tissue (Longissimus dorsi of right half-carcass in 45 minutes, 2, 3, 4, 5, 6 hours and 24 hours after slaughter. Results were statistically elaborated using one-way variance analysis. Longissimus dorsi muscle pH values measured 45 minutes after slaughter in case of all groups of pigs were in range from 6.34 up to 6.47, what shows good meat quality. The lowest pH1 (measured 45 minutes after slaughter had meat of fatteners where addition of 2 % sunflower oil was given into fodder and the highest value of this trait was in group of individuals where also was given sunflower oil in 1 % amount. Statistical significant differences in pH value measured in different time after slaughter i.e. after 45 minutes, 2, 3, 4, 6 and 24 hours between tested groups of pigs were not stated. The exception is the result of pH measurement 5 hours after slaughter. Statistical significant differences were between group of pigs getting 0.5 % addition of conjugated linoleic acid characterized by the highest pH value of meat and group of animals fed the fodder with 1 % addition of conjugated linoleic acid (P≤0.01. On the basis of the results obtained in presented paper may be stated that feeding pigs with addition of conjugated linoleic acid in amounts 0.5; 1.0 and 2.0 % did not impact negatively on meat quality defined by pH value.

  12. Conjugated linoleic acid supplementation caused reduction of perilipin1 and aberrant lipolysis in epididymal adipose tissue

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Demin [College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Li, Hongji [Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Zhou, Bo [College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Han, Liqiang [Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Zhang, Xiaomei [College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Yang, Guoyu, E-mail: haubiochem@163.com [Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Yang, Guoqing, E-mail: gqyang@yeah.net [College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China)

    2012-06-15

    Highlights: Black-Right-Pointing-Pointer Conjugated linoleic acid supplementation suppresses perilipin1 in epididymal fat. Black-Right-Pointing-Pointer Conjugated linoleic acid inhibits promoter activity of perilipin1 in 3T3-L1 cells. Black-Right-Pointing-Pointer Conjugated linoleic acids elevate basal but blunt hormone-stimulated lipolysis. -- Abstract: Perilipin1, a coat protein of lipid droplet, plays a key role in adipocyte lipolysis and fat formation of adipose tissues. However, it is not clear how the expression of perilipin1 is affected in the decreased white adipose tissues (WAT) of mice treated with dietary supplement of conjugated linoleic acids (CLA). Here we obtained lipodystrophic mice by dietary administration of CLA which exhibited reduced epididymal (EPI) WAT, aberrant adipocytes and decreased expression of leptin in this tissue. We found both transcription and translation of perilipin1 was suppressed significantly in EPI WAT of CLA-treated mice compared to that of control mice. The gene expression of negative regulator tumor necrosis factor {alpha} (TNF{alpha}) and the positive regulator Peroxisome Proliferator-Activated Receptor-{gamma} (PPAR{gamma}) of perilipin1 was up-regulated and down-regulated, respectively. In cultured 3T3-L1 cells the promoter activity of perilipin1 was dramatically inhibited in the presence of CLA. Using ex vivo experiment we found that the basal lipolysis was elevated but the hormone-stimulated lipolysis blunted in adipose explants of CLA-treated mice compared to that of control mice, suggesting that the reduction of perilipin1 in white adipose tissues may at least in part contribute to CLA-mediated alternation of lipolysis of WAT.

  13. Bioactive metabolites of docosahexaenoic acid

    Czech Academy of Sciences Publication Activity Database

    Kuda, Ondřej

    2017-01-01

    Roč. 136, May (2017), s. 12-20 ISSN 0300-9084 R&D Projects: GA ČR(CZ) GA16-04859S; GA MZd(CZ) NV16-29182A Institutional support: RVO:67985823 Keywords : DHA * specialized proresolving mediators * FAHFA * DHEA * N-acyl amides * omega-3 PUFA Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition OBOR OECD: Endocrinology and metabolism (including diabetes, hormones) Impact factor: 3.112, year: 2016

  14. Bioavailability of Echinacea Constituents: Caco-2 Monolayers and Pharmacokinetics of the Alkylamides and Caffeic Acid Conjugates

    Directory of Open Access Journals (Sweden)

    R. Lehmann

    2005-10-01

    Full Text Available Many studies have been done over the years to assess the effectiveness of Echinacea as an immunomodulator. We have assessed the potential bioavailability of alkyl- amides and caffeic acid conjugates using Caco-2 monolayers and compared it to their actual bioavailability in a Phase I clinical trial. The caffeic acid conjugates permeated poorly through the Caco-2 monolayers. Alkylamides were found to diffuse rapidly through Caco-2 monolayers. Differences in diffusion rates for each alkylamide correlated to structural variations, with saturation and N-terminal methylation contributing to decreases in diffusion rates. Alkylamide diffusion is not affected by the presence of other constituents and the results for a synthetic alkylamide were in line with those for alkylamides found in an ethanolic Echinacea preparation. We examined plasma from healthy volunteers for 12 hours after ingestion of Echinacea tablets manufactured from an ethanolic liquid extract. Caffeic acid conjugates could not be identified in any plasma sample at any time after tablet ingestion. Alkylamides were detected in plasma 20 minutes after tablet ingestion and for each alkylamide, pharmacokinetic profiles were devised. The data are consistent with the dosing regimen of one tablet three times daily and supports their usage as the primary markers for quality Echinacea preparations.

  15. Improved cellular activity of antisense peptide nucleic acids by conjugation to a cationic peptide-lipid (CatLip) domain

    DEFF Research Database (Denmark)

    Koppelhus, Uffe; Shiraishi, Takehiko; Zachar, Vladimir

    2008-01-01

    Conjugation to cationic cell penetrating peptides (such as Tat, Penetratin, or oligo arginines) efficiently improves the cellular uptake of large hydrophilic molecules such as oligonucleotides and peptide nucleic acids, but the cellular uptake is predominantly via an unproductive endosomal pathway...... for future in vivo applications. We find that simply conjugating a lipid domain (fatty acid) to the cationic peptide (a CatLip conjugate) increases the biological effect of the corresponding PNA (CatLip) conjugates in a luciferase cellular antisense assay up to 2 orders of magnitude. The effect increases...... with increasing length of the fatty acid (C8-C16) but in parallel also results in increased cellular toxicity, with decanoic acid being optimal. Furthermore, the relative enhancement is significantly higher for Tat peptide compared to oligoarginine. Confocal microscopy and chloroquine enhancement indicates...

  16. Evaluation of the hepatic bioconversion of α-linolenic acid (ALA to eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA in rats fed with oils from chia (Salvia hispánica or rosa mosqueta (Rosa rubiginosa

    Directory of Open Access Journals (Sweden)

    Tapia O., G.

    2012-03-01

    Full Text Available The high dietary intake of n-6 fatty acids in relation to n-3 fatty acids generates health disorders, such as cardiovascular diseases, inflammatory diseases and other chronic diseases. The consumption of fish, which is rich in n-3 fatty acids, is low in Latin America and it is necessary to seek other alternatives, such as chia oil (CO or rosa mosqueta oil (RMO, which are rich in α-linolenic acid (ALA, the precursor of the n -3 fatty acids, eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA. This study evaluates the hepatic bioconversion of ALA to EPA and DHA and the damage to the liver (histology and transaminase in Sprague- Dawley rats fed different vegetable oils. Four experimental groups (n = 9 animals each group were fed the following dietary supplements for 21 days: a sunflower oil (SFO, b RMO, c CO d olive oil with fish oil added (EPA and DHA (OO/FO. RMO and CO increased the hepatic levels of ALA, EPA and DHA and decreased the n-6/n-3 ratio compared to SFO (p El elevado aporte en la dieta de ácidos grasos omega- 6, en relación a los ácidos grasos omega-3, genera alteraciones de la salud cardiovascular, inflamación y otras patologías crónicas no transmisibles. Por otro lado, el pescado rico en ácidos grasos omega-3 es de bajo consumo en Latinoamérica, siendo necesario buscar otras alternativas de aporte de ácidos grasos omega-3, como lo son el aceite de chía (CO o el de rosa mosqueta (RMO, ricos en ácido α-linolénico (ALA, que es el precursor de los ácidos grasos omega-3, eicosapentaenoico (EPA y docosahexaenoico (DHA. Este trabajo evaluó en forma preliminar la bioconversión hepática del ALA en EPA y DHA y el daño hepático (histología y transaminasas en ratas Sprague-Dawley alimentadas con diferentes aceites vegetales. Se conformaron cuatro grupos experimentales (n = 9 animales por grupo que recibieron durante 21 días: a aceite de girasol (SFO; b RMO, c CO y d aceite de oliva adicionado de aceite de pescado (EPA

  17. Gallic acid conjugated with gold nanoparticles: antibacterial activity and mechanism of action on foodborne pathogens.

    Science.gov (United States)

    Rattanata, Narintorn; Klaynongsruang, Sompong; Leelayuwat, Chanvit; Limpaiboon, Temduang; Lulitanond, Aroonlug; Boonsiri, Patcharee; Chio-Srichan, Sirinart; Soontaranon, Siriwat; Rugmai, Supagorn; Daduang, Jureerut

    2016-01-01

    Foodborne pathogens, including Plesiomonas shigelloides and Shigella flexneri B, are the major cause of diarrheal endemics worldwide. Antibiotic drug resistance is increasing. Therefore, bioactive compounds with antibacterial activity, such as gallic acid (GA), are needed. Gold nanoparticles (AuNPs) are used as drug delivery agents. This study aimed to conjugate and characterize AuNP-GA and to evaluate the antibacterial activity. AuNP was conjugated with GA, and the core-shell structures were characterized by small-angle X-ray scattering and transmission electron microscopy. Antibacterial activity of AuNP-GA against P. shigelloides and S. flexneri B was evaluated by well diffusion method. AuNP-GA bactericidal mechanism was elucidated by Fourier transform infrared microspectroscopic analysis. The results of small-angle X-ray scattering showed that AuNP-GA conjugation was successful. Antibacterial activity of GA against both bacteria was improved by conjugation with AuNP because the minimum inhibitory concentration value of AuNP-GA was significantly decreased (Pacids at the bacterial cell membrane. Our findings show that AuNP-GA has potential for further application in biomedical sciences.

  18. Role of 5-aminolevulinic acid-conjugated gold nanoparticles for photodynamic therapy of cancer

    Science.gov (United States)

    Zhang, Zhenxi; Wang, Sijia; Xu, Hao; Wang, Bo; Yao, Cuiping

    2015-05-01

    There are three possible mechanisms for 5-aminolevulinic acid (5-ALA) conjugated gold nanoparticles (GNPs) through electrostatic bonding for photodynamic therapy (PDT) of cancer: GNPs delivery function, singlet oxygen generation (SOG) by GNPs irradiated by light, and surface resonance enhancement (SRE) of SOG. Figuring out the exact mechanism is important for further clinical treatment. 5-ALA-GNPs and human chronic myeloid leukemia K562 cells were used to study delivery function and SOG by GNPs. The SRE of SOG enabled by GNPs was explored by protoporphyrin IX (PpIX)-GNPs conjugate through electrostatic bonding. Cell experiments show that the GNPs can improve the efficiency of PDT, which is due to the vehicle effect of GNPs. PpIX-GNPs conjugate experiments demonstrated that SOG can be improved about 2.5 times over PpIX alone. The experiments and theoretical results show that the local field enhancement (LFE) via localized surface plasmon resonance (LSPR) of GNPs is the major role; the LFE was dependent on the irradiation wavelength and the GNP's size. The LFE increased with an increase of the GNP size (2R ≤50 nm). However, the LSPR function of the GNPs was not found in cell experiments. Our study shows that in 5-ALA-conjugated GNPs PDT, the delivery function of GNPs is the major role.

  19. Sulfated Steroid–Amino Acid Conjugates from the Irish Marine Sponge Polymastia boletiformis

    Directory of Open Access Journals (Sweden)

    Vangelis Smyrniotopoulos

    2015-03-01

    Full Text Available Antifungal bioactivity-guided fractionation of the organic extract of the sponge Polymastia boletiformis, collected from the west coast of Ireland, led to the isolation of two new sulfated steroid-amino acid conjugates (1 and 2. Extensive 1D and 2D NMR analyses in combination with quantum mechanical calculations of the electronic circular dichroism (ECD spectra, optical rotation, and 13C chemical shifts were used to establish the chemical structures of 1 and 2. Both compounds exhibited moderate antifungal activity against Cladosporium cucumerinum, while compound 2 was also active against Candida albicans. Marine natural products containing steroidal and amino acid constituents are extremely rare in nature.

  20. Sulfated steroid-amino acid conjugates from the Irish marine sponge Polymastia boletiformis.

    Science.gov (United States)

    Smyrniotopoulos, Vangelis; Rae, Margaret; Soldatou, Sylvia; Ding, Yuanqing; Wolff, Carsten W; McCormack, Grace; Coleman, Christina M; Ferreira, Daneel; Tasdemir, Deniz

    2015-03-24

    Antifungal bioactivity-guided fractionation of the organic extract of the sponge Polymastia boletiformis, collected from the west coast of Ireland, led to the isolation of two new sulfated steroid-amino acid conjugates (1 and 2). Extensive 1D and 2D NMR analyses in combination with quantum mechanical calculations of the electronic circular dichroism (ECD) spectra, optical rotation, and 13C chemical shifts were used to establish the chemical structures of 1 and 2. Both compounds exhibited moderate antifungal activity against Cladosporium cucumerinum, while compound 2 was also active against Candida albicans. Marine natural products containing steroidal and amino acid constituents are extremely rare in nature.

  1. Efficacy of peptide nucleic acid and selected conjugates against specific cellular pathologies of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Browne, Elisse C; Parakh, Sonam; Duncan, Luke F; Langford, Steven J; Atkin, Julie D; Abbott, Belinda M

    2016-04-01

    Cellular studies have been undertaken on a nonamer peptide nucleic acid (PNA) sequence, which binds to mRNA encoding superoxide dismutase 1, and a series of peptide nucleic acids conjugated to synthetic lipophilic vitamin analogs including a recently prepared menadione (vitamin K) analog. Reduction of both mutant superoxide dismutase 1 inclusion formation and endoplasmic reticulum stress, two of the key cellular pathological hallmarks in amyotrophic lateral sclerosis, by two of the prepared PNA oligomers is reported for the first time. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  2. Benzoylated Uronic Acid Building Blocks and Synthesis of N-Uronate Conjugates of Lamotrigine

    Directory of Open Access Journals (Sweden)

    Bård Helge Hoff

    2012-01-01

    Full Text Available A chemoenzymatic approach towards benzoylated uronic acid building blocks has been investigated starting with benzoylated hexapyranosides using regioselective C-6 enzymatic hydrolysis as the key step. Two of the building blocks were reacted with the antiepileptic drug lamotrigine. Glucuronidation of lamotrigine using methyl (2,3,4-tri-O-benzoyl-α-D-glycopyranosyl bromideuronate proceeded to give the N2-conjugate. However, lamotrigine-N2-glucuronide was most efficiently synthesised from methyl (2,3,4-tri-O-acetyl-α-D-glucopyranosyl bromideuronate. Employing nitromethane as solvent with CdCO3 as a base lamotrigine-N2 glucuronide was prepared in a high yield (41%. Also methyl (2,3-di-O-benzoyl-4-deoxy-4-fluoro-α-D-glucosyl bromideuronate underwent N-glucuronidation, but the product was unstable, eliminating hydrogen fluoride to give the corresponding enoate conjugate.

  3. Eicosapentaenoic acid and docosahexaenoic acid in whole blood are differentially and sex-specifically associated with cardiometabolic risk markers in 8-11-year-old danish children

    DEFF Research Database (Denmark)

    Damsgaard, Camilla T.; Eidner, Maj B.; Stark, Ken D.

    2014-01-01

    -day dietary records, physical activity by accelerometry and measured anthropometry, blood pressure, and heart rate. Blood samples were analyzed for whole blood fatty acid composition, cholesterols, triacylglycerol, insulin resistance by the homeostatic model of assessment (HOMA-IR), and inflammatory...

  4. Light enhanced the accumulation of total fatty acids (TFA) and docosahexaenoic acid (DHA) in a newly isolated heterotrophic microalga Crypthecodinium sp. SUN.

    Science.gov (United States)

    Sun, Dongzhe; Zhang, Zhao; Mao, Xuemei; Wu, Tao; Jiang, Yue; Liu, Jin; Chen, Feng

    2017-03-01

    In the present study, light illumination was found to be efficient in elevating the total fatty acid content in a newly isolated heterotrophic microalga, Crypthecodinium sp. SUN. Under light illumination, the highest total fatty acid and DHA contents were achieved at 96h as 24.9% of dry weight and 82.8mgg -1 dry weight, respectively, which were equivalent to 1.46-fold and 1.68-fold of those under the dark conditions. The elevation of total fatty acid content was mainly contributed by an increase of neutral lipids at the expense of starches. Moreover, light was found to alter the cell metabolism and led to a higher specific growth rate, higher glucose consumption rate and lower non-motile cell percentage. This is the first report that light can promote the total fatty acids accumulation in Crypthecodinium without growth inhibition. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Supplementing female rats with DHA-lysophosphatidylcholine increases docosahexaenoic acid and acetylcholine contents in the brain and improves the memory and learning capabilities of the pups.

    Directory of Open Access Journals (Sweden)

    Rojas, I.

    2010-03-01

    Full Text Available Docosahexaenoic acid (DHA is supplied to the foetus and newborn through the mother from their own reserves and their diet. No consensus about the best form to supplement DHA has been established. We propose that DHAcontaining lysophosphatidylcholine (DHA-LPC, obtained from DHA-rich eggs may be a suitable form of DHA and choline (the precursor of acetylcholine supplementation. We evaluated the effectiveness of DHA-LPC to increase DHA and acetylcholine concentration in the brain of pups born from female rats supplemented with DHA-LPC before and during pregnancy. We also evaluated the effect of DHA supplementation on learning and memory capabilities of pups through the Skinner test for operant conditioning. Female Wistar rats received 40-day supplementation of DHA-LPC (8 mg DHA/kg b.w/daily., before and during pregnancy. After delivery, plasma, erythrocyte, liver, and adipose tissue DHA and plasma choline were analyzed. Brains from 60 day-old pups separated into frontal cortex, cerebellum, striatum, hippocampus, and occipital cortex, were assessed for DHA, acetylcholine, and acetylcholine transferase (CAT activity. Pups were subjected to the Skinner box test. DHA-LPC supplementation produces higher choline and liver DHA contents in the mother’s plasma and increases the pups’ DHA and acetylcholine in the cerebellum and hippocampus. CAT was not modified by supplementation. The Skinner test shows that pups born from DHA-LPC supplemented mothers exhibit better scores of learning and memory than the controls. Conclusion: DHA-LPC may be an adequate form for DHA supplementation during the perinatal period.El ácido docosahexaenoico (DHA que requiere el feto y el recién nacido lo aporta la madre desde sus reservas y la dieta, por lo cual se sugiere suplementar a la madre con DHA. No hay consenso sobre la mejor forma de suplementación. Proponemos que un lisofosfolípido que contiene DHA y colina (DHA-LPC obtenido de huevos con alto contenido de DHA es

  6. Free-radical-mediated conjugate additions. Enantioselective synthesis of butyrolactone natural products: (-)-enterolactone, (-)-arctigenin, (-)-isoarctigenin, (-)-nephrosteranic acid, and (-)-roccellaric acid.

    Science.gov (United States)

    Sibi, Mukund P; Liu, Pingrong; Ji, Jianguo; Hajra, Saumen; Chen, Jian-xie

    2002-03-22

    Lewis acid-mediated conjugate addition of alkyl radicals to a differentially protected fumarate 10 produced the monoalkylated succinates with high chemical efficiency and excellent stereoselectivity. A subsequent alkylation or an aldol reaction furnished the disubstituted succinates with syn configuration. The chiral auxiliary, 4-diphenylmethyl-2-oxazolidinone, controlled the stereoselectivity in both steps. Manipulation of the disubstituted succinates obtained by alkylation furnished the natural products (-)-enterolactone, (-)-arctigenin, and (-)-isoarctigenin. The overall yields for the target natural products were 20-26% over six steps. Selective functionalization of the disubstituted succinates obtained by aldol condensation gave the paraconic acid natural products (-)-nephrosteranic acid (8) and (-)-roccellaric acid (9). The overall yield of the natural products 8 and 9 over four steps was 53% and 42%, respectively.

  7. Bovine milk fat enriched in conjugated linoleic and vaccenic acids attenuates allergic airway disease in mice.

    Science.gov (United States)

    Kanwar, R K; Macgibbon, A K; Black, P N; Kanwar, J R; Rowan, A; Vale, M; Krissansen, G W

    2008-01-01

    It has been argued that a reduction in the Western diet of anti-inflammatory unsaturated lipids, such as n-3 polyunsaturated fatty acids, has contributed to the increase in the frequency and severity of allergic diseases. We investigated whether feeding milk fat enriched in conjugated linoleic acid and vaccenic acids (VAs) ('enriched' milk fat), produced by supplementing the diet of pasture-fed cows with fish and sunflower oil, will prevent development of allergic airway responses. C57BL/6 mice were fed a control diet containing soybean oil and diets supplemented with milk lipids. They were sensitized by intraperitoneal injection of ovalbumin (OVA) on days 14 and 28, and challenged intranasally with OVA on day 42. Bronchoalveolar lavage fluid, lung tissues and serum samples were collected 6 days after the intranasal challenge. Feeding of enriched milk fat led to marked suppression of airway inflammation as evidenced by reductions in eosinophilia and lymphocytosis in the airways, compared with feeding of normal milk fat and control diet. Enriched milk fat significantly reduced circulating allergen-specific IgE and IgG1 levels, together with reductions in bronchoalveolar lavage fluid of IL-5 and CCL11. Treatment significantly inhibited changes in the airway including airway epithelial cell hypertrophy, goblet cell metaplasia and mucus hypersecretion. The two major components of enriched milk fat, cis-9, trans-11 conjugated linoleic acid and VA, inhibited airway inflammation when fed together to mice, whereas alone they were not effective. Milk fat enriched in conjugated linoleic and VAs suppresses inflammation and changes to the airways in an animal model of allergic airway disease.

  8. Effect of eicosapentaenoic acid/docosahexaenoic acid on coronary high-intensity plaques detected with non-contrast T1-weighted imaging (the AQUAMARINE EPA/DHA study): study protocol for a randomized controlled trial.

    Science.gov (United States)

    Nakao, Kazuhiro; Noguchi, Teruo; Asaumi, Yasuhide; Morita, Yoshiaki; Kanaya, Tomoaki; Fujino, Masashi; Hosoda, Hayato; Yoneda, Shuichi; Kawakami, Shoji; Nagai, Toshiyuki; Nishihira, Kensaku; Nakashima, Takahiro; Kumasaka, Reon; Arakawa, Tetsuo; Otsuka, Fumiyuki; Nakanishi, Michio; Kataoka, Yu; Tahara, Yoshio; Goto, Yoichi; Yamamoto, Haruko; Hamasaki, Toshimitsu; Yasuda, Satoshi

    2018-01-08

    Despite the success of HMG-CoA reductase inhibitor (statin) therapy in reducing atherosclerotic cardiovascular events, a residual risk for cardiovascular events in patients with coronary artery disease (CAD) remains. Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are promising anti-atherosclerosis agents that might reduce the residual CAD risk. Non-contrast T1-weighted imaging (T1WI) with cardiac magnetic resonance (CMR) less invasively identifies high-risk coronary plaques as high-intensity signals. These high-intensity plaques (HIPs) are quantitatively assessed using the plaque-to-myocardium signal intensity ratio (PMR). Our goal is to assess the effect of EPA/DHA on coronary HIPs detected with T1WI in patients with CAD on statin treatment. This prospective, controlled, randomized, open-label study examines the effect of 12 months of EPA/DHA therapy and statin treatment on PMR of HIPs detected with CMR and computed tomography angiography (CTA) in patients with CAD. The primary endpoint is the change in PMR after EPA/DHA treatment. Secondary endpoints include changes in Hounsfield units, plaque volume, vessel area, and plaque area measured using CTA. Subjects are randomly assigned to either of three groups: the 2 g/day EPA/DHA group, the 4 g/day EPA/DHA group, or the no-treatment group. This trial will help assess whether EPA/DHA has an anti-atherosclerotic effect using PMR of HIPs detected by CMR. The trial outcomes will provide novel insights into the effect of EPA/DHA on high-risk coronary plaques and may provide new strategies for lowering the residual risk in patients with CAD on statin therapy. The University Hospital Medical Information Network (UMIN) Clinical Trials Registry, ID: UMIN000015316 . Registered on 2 October 2014.

  9. Properties of acid gels made from sodium caseinate-maltodextrin conjugates prepared by a wet heating method.

    Science.gov (United States)

    Zhang, Shuwen; Gong, Yuansheng; Khanal, Som; Lu, Yanjie; Lucey, John A

    2017-11-01

    Covalent attachment of polysaccharides to proteins (conjugation) via the Maillard reaction has been extensively studied. Conjugation can lead to a significant improvement in protein functionality (e.g., solubility, emulsification, and heat stability). Caseins have previously been successfully conjugated with maltodextrin (Md), but the effect on the detailed acid gelation properties has not been examined. We studied the effect of conjugating sodium caseinate (NaCN) with 3 different sized Md samples via the Maillard reaction in aqueous solutions. The Md samples had dextrose equivalents of 4 to 7, 9 to 12, and 20 to 23 for Md40, Md100, and Md200, respectively. The conjugation reaction was performed in mixtures with 5% NaCN and 5% Md, which were heated at 90°C for 10 h. The degree of conjugation was estimated from the reduction in free amino groups as well as color changes. Sodium dodecyl sulfate-PAGE analysis was performed to confirm conjugation by employing staining of both protein and carbohydrate bands. The molar mass of samples was determined by size-exclusion chromatography coupled with multi-angle laser light scattering. After the conjugation reaction, samples were then gelled by the addition of 0.63% (wt/vol) glucono-δ-lactone at 30°C, such that samples reached pH 4.6 after about 13 h. The rheological properties of samples during acidification was monitored by small-strain dynamic oscillatory rheology. The microstructure of acid gels at pH 4.6 was examined by fluorescence microscopy. Conjugation resulted in a loss of 10.8, 8.8, and 11.9% of the available amino groups in the protein for the NaCN-Md40 conjugates (C40), NaCN-Md100 conjugates (C100), and NaCN-Md100 conjugates (C200), respectively. With a decrease in the size of the type of Md, an increase occurred in the molar mass of the resultant conjugate. The weight average molar masses of NaCN-Md samples were 340, 368, and 425 kDa for the conjugates C40, C100, and C200, respectively. Addition of Md to Na

  10. Amide-conjugated indole-3-acetic acid and adventitious root formation in mung bean cuttings

    International Nuclear Information System (INIS)

    Norcini, J.G.

    1986-01-01

    The purpose of this research was to investigate further the relationship between amide-conjugated auxin and adventitious root formation. Indoleacetylaspartic acid (IAA-aspartate) was positively identified as the predominant conjugate isolated from mung bean cuttings after the cuttings has been treated with 10 -3 M IAA. In cuttings treated with [1- 14 C]IAA immediately after excision (0 hr), the percent of extractable 14 C in IAA-aspartate in the hypocotyl sharply increased until 36 hr, then steadily declined. [ 14 C]IAA was completely metabolized between 12 and 24 hr. The rooting activities of IAA-L-aspartate, IAA-L-alanine, and IAA-glycine were determined at various stages of root formation; some cuttings were pretreated with 10 -3 M IAA at 0 hr. Pretreated cuttings that were treated with IAA-glycine at 12, 24, 36 hr exhibited the greatest consistency between replications, the greatest number of long roots, and the longest roots. The conjugates did not stimulate rooting as effectively as IAA, yet like IAA, generally enhanced rooting the greatest when applied before the first cell division (24 hr)

  11. Interaction of conjugated bile acids and detergents with a radiosorbent assay of vitamin B-12

    International Nuclear Information System (INIS)

    Andersen, K.-J.; Romslo, I.

    1977-01-01

    The effect of conjugated bile acids and detergents on the radiosorbent technique for the determination of vitamin B-12 activity is reported. It is shown that whereas the non-ionic detergent Triton X-100 has no effect on the vitamin B-12-radiosorbent assay, the addition of ionic detergents, e.g. glycocholic acid, taurocholic acid or sodium lauryl sulfate, results in a falsely-elevated vitamin B-12 activity presumably due to the disruption of the binding of vitamin B-12 to the intrinsic factor-Sephadex complex. This effect may be of importance not only to the radiosorbent assaying of vitamin B-12, but to the in vivo intestinal absorption of vitamin B-12 as well

  12. Improved separation of conjugated fatty acid methyl esters by silver ion-high-performance liquid chromatography.

    Science.gov (United States)

    Sehat, N; Rickert, R; Mossoba, M M; Kramer, J K; Yurawecz, M P; Roach, J A; Adlof, R O; Morehouse, K M; Fritsche, J; Eulitz, K D; Steinhart, H; Ku, Y

    1999-04-01

    Operating from one to six silver ion-high-performance liquid chromatography (Ag+-HPLC) columns in series progressively improved the resolution of the methyl esters of conjugated linoleic acid (CLA) isomeric mixtures from natural and commercial products. In natural products, the 8 trans, 10 cis-octadecadienoic (18:2) acid was resolved from the more abundant 7 trans, 9 cis-18:2, and the 10 trans, 12 cis-18:2 was separated from the major 9 cis, 11 trans-18:2 peak. In addition, both 11 trans, 13 cis-18:2 and 11 cis, 13 trans-18:2 isomers were found in natural products and were separated; the presence of the latter, 11 cis, 13 trans-18:2, was established in commercial CLA preparations. Three Ag+-HPLC columns in series appeared to be the best compromise to obtain satisfactory resolution of most CLA isomers found in natural products. A single Ag+-HPLC column in series with one of several normal-phase columns did not improve the resolution of CLA isomers as compared to that of the former alone. The 20:2 conjugated fatty acid isomers 11 cis, 13 trans-20:2 and 12 trans, 14 cis-20:2, which were synthesized by alkali isomerization from 11 cis, 14 cis-20:2, eluted in the same region of the Ag+-HPLC chromatogram just before the corresponding geometric CLA isomers. Therefore, CLA isomers will require isolation based on chain length prior to Ag+-HPLC separation. The positions of conjugated double bonds in 20:2 and 18:2 isomers were established by gas chromatography-electron ionization mass spectrometry as their 4,4-dimethyloxazoline derivatives. The double-bond geometry was determined by gas chromatography-direct deposition-Fourier transform infrared spectroscopy and by the Ag+-HPLC relative elution order.

  13. The Effects of Nano-encapsulated Conjugated Linoleic Acid on Stability of Conjugated Linoleic Acid and Fermentation Profiles in the Rumen

    Directory of Open Access Journals (Sweden)

    Wan Heo

    2016-03-01

    Full Text Available This study was aimed to evaluate the stability of conjugated linoleic acids (CLAs by nano-encapsulation against in vitro ruminal biohydrogenation by microbial enzymatic conversion. CLAs (free fatty acid form of CLA [CLA-FFA], nano-encapsulated CLA-FFA, triglyceride form of CLA [CLA-TG], and nano-encapsulated CLA-TG were used in the in vitro fermentation experiments. When Butyrivibrio fibrisolvens (B. fibrisolvens was incubated with CLA-FFAs, the concentrations of cis-9, trans-11 CLA and vaccenic acid (VA slightly was decreased and increased by nano-encapsulation, respectively. When B. fibrisolvens was incubated with CLA-TG, the concentrations of cis-9, trans-11 CLA and VA decreased, but these were increased when B. fibrisolvens was incubated with nano-encapsulated CLA-TG. The nano-encapsulation was more effective against the in vitro biohydrogenation activity of B.fibrisolvens incubated with CLA-FFA than with CLA-TG. In the in vitro ruminal incubation test, the total gas production and concentration of total volatile fatty acids incubated with nano-encapsulated CLA-FFA and CLA-TG were increased significantly after 24 h incubation (p<0.05. Nano-encapsulated CLA-FFA might, thus, improve the ruminal fermentation characteristics without adverse effects on the incubation process. In addition, nano-encapsulated CLA-FFA increased the population of Fibrobacter succinogenes and decreased the population of B. fibrisolvens population. These results indicate that nano-encapsulation could be applied to enhance CLA levels in ruminants by increasing the stability of CLA without causing adverse effects on ruminal fermentation.

  14. The Conjugates of Phenolic Acids in Lichens of the Order Lecanorales

    Directory of Open Access Journals (Sweden)

    T. N. NIKOLAEVA

    2014-06-01

    Full Text Available Lichens are symbiotic associations of a fungus (usually an ascomycete and a photobiont, which may be an alga and/or a cyanobacterium. Lichens dominate on about 6–8% of land surface, mainly in the habitats with severe climatic conditions. Lichenized fungi are among the pioneer vegetation on bare rock or soil. Mat-forming species contribute substantially to the soil cover in tundras and high mountain elevations. Lichens are rich in water-soluble compounds which can be leached-out the lichen thalli with atmospheric depositions. We have recently described the occurrence of water-soluble phenolics in lichens (Zagoskina et al 2013. These compounds can play important role in the ecosystem functioning and primary soil formation (weathering, humification. The aim of this work was to study qualitative composition of water-soluble phenolics in the lichen species widespread in the soil cover of tundra zone. The air-dried thalli of Alectoria ochroleuca, Cetraria islandica, C.nigricans, C.nivalis, Cladonia arbuscula and C.stellaris were homogenized to powder and used for the study. Lichens were collected in Khibiny mountains, Kola Peninsula in August 2013. Phenolic compounds were extracted by distilled water (1h, 30C and analyzed by TLC before and after the acid hydrolysis. It was found that all the lichens under the study contained the conjugates of phenol carboxylic acids. We have identified that non-phenolic part in some of these conjugates was represented by sugars and amino acids. The TLC of the hydrolizates of water extracts revealed occurrence of p-oxybenzoic acid in all of the species studied. The lichens Cetraria islandica, С.nigricans and Cladonia stellaris contained also vanillic acid. These phenolic acids are widespread in plant kingdom and are known as products of lignin decomposition in higher plants. The physiological role of water-soluble phenolics in lichens as well as their environmental role are need to be understood in future studies.

  15. Synthesis of nucleotide–amino acid conjugates designed for photo-CIDNP experiments by a phosphotriester approach

    Directory of Open Access Journals (Sweden)

    Tatyana V. Abramova

    2013-12-01

    Full Text Available Conjugates of 2’-deoxyguanosine, L-tryptophan and benzophenone designed to study pathways of fast radical reactions by the photo Chemically Induced Dynamic Nuclear Polarization (photo-CIDNP method were obtained by the phosphotriester block liquid phase synthesis. The phosphotriester approach to the oligonucleotide synthesis was shown to be a versatile and economic strategy for preparing the required amount of high quality samples of nucleotide–amino acid conjugates.

  16. Dietary structured triacylglycerols containing docosahexaenoic acid given from birth affect visual and auditory performance and tissue fatty acid profiles of rats

    DEFF Research Database (Denmark)

    Christensen, M. M.; Lund, S. P.; Simonsen, L.

    1998-01-01

    To examine whether it is possible to enhance the level of 22:6(n-3) in the central nervous system, newborn rats were fed dietary supplements containing oils with either specific or random triacylglycerol structure, but similar concentrations of polyunsaturated fatty acids. In the specific structu...... in differences in learning ability, but caused changes in visual function, evidenced by higher latency of the b-wave and lower oscillatory potential, and in auditory brainstem response, evidenced by generally greater amplitude of wave la in the group fed specific structured oil....

  17. Influence of organic diet on the amount of conjugated linoleic acids in breast milk of lactating women in the Netherlands

    NARCIS (Netherlands)

    Rist, L.; Mueller, A.; Barthel, C.; Snijders, B.; Jansen, M.; Simões-Wüst, A.P.; Huber, M.; Kummeling, I.; Mandach, U. von; Steinhart, H.; Thijs, C.

    2007-01-01

    The aim of the present study was to find out whether the incorporation of organic dairy and meat products in the maternal diet affects the contents of the conjugated linoleic acid isomers (CLA) and trans-vaccenic acid (TVA) in human breast milk. To this purpose, milk samples from 312 breastfeeding

  18. Effects of cholesterol oxides on cell death induction and calcium increase in human neuronal cells (SK-N-BE) and evaluation of the protective effects of docosahexaenoic acid (DHA; C22:6 n-3).

    Science.gov (United States)

    Zarrouk, Amira; Nury, Thomas; Samadi, Mohammad; O'Callaghan, Yvonne; Hammami, Mohamed; O'Brien, Nora M; Lizard, Gérard; Mackrill, John J

    2015-07-01

    Some oxysterols are associated with neurodegenerative diseases. Their lipotoxicity is characterized by an oxidative stress and induction of apoptosis. To evaluate the capacity of these molecules to trigger cellular modifications involved in neurodegeneration, human neuronal cells SK-N-BE were treated with 7-ketocholesterol, 7α- and 7β-hydroxycholesterol, 6α- and 6β-hydroxycholesterol, 4α- and 4β-hydroxycholesterol, 24(S)-hydroxycholesterol and 27-hydroxycholesterol (50-100μM, 24h) without or with docosahexaenoic acid (50μM). The effects of these compounds on mitochondrial activity, cell growth, production of reactive oxygen species (ROS) and superoxide anions (O2(-)), catalase and superoxide dismutase activities were determined. The ability of the oxysterols to induce increases in Ca(2+) was measured after 10min and 24h of treatment using fura-2 videomicroscopy and Von Kossa staining, respectively. Cholesterol, 7-ketocholesterol, 7β-hydroxycholesterol, and 24(S)-hydroxycholesterol (100μM) induced mitochondrial dysfunction, cell growth inhibition, ROS overproduction and cell death. A slight increase in the percentage of cells with condensed and/or fragmented nuclei, characteristic of apoptotic cells, was detected. With 27-hydroxycholesterol, a marked increase of O2(-) was observed. Increases in intracellular Ca(2+) were only found with 7-ketocholesterol, 7β-hydroxycholesterol, 24(S)-hydroxycholesterol and 27-hydroxycholesterol. Pre-treatment with docosahexaenoic acid showed some protective effects depending on the oxysterol considered. According to the present data, 7-ketocholesterol, 7β-hydroxycholesterol, 24(S)-hydroxycholesterol and 27-hydroxycholesterol could favor neurodegeneration by their abilities to induce mitochondrial dysfunctions, oxidative stress and/or cell death associated or not with increases in cytosolic calcium levels. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Investigating the chemical changes of chlorogenic acids during coffee brewing: conjugate addition of water to the olefinic moiety of chlorogenic acids and their quinides.

    Science.gov (United States)

    Matei, Marius Febi; Jaiswal, Rakesh; Kuhnert, Nikolai

    2012-12-12

    Coffee is one of the most popular and consumed beverages in the world and is associated with a series of benefits for human health. In this study we focus on the reactivity of chlorogenic acids, the most abundant secondary metabolites in coffee, during the coffee brewing process. We report on the hydroxylation of the chlorogenic acid cinnamoyl substituent by conjugate addition of water to form 3-hydroxydihydrocaffeic acid derivatives using a series of model compounds including monocaffeoyl and dicaffeoylquinic acids and quinic acid lactones. The regiochemistry of conjugate addition was established based on targeted tandem MS experiments. Following conjugate addition of water a reversible water elimination yielding cis-cinnamoyl derivatives accompanied by acyl migration products was observed in model systems. We also report the formation of all of these derivatives during the coffee brewing process.

  20. Engineering the production of conjugated fatty acids in Arabidopsis thaliana leaves.

    Science.gov (United States)

    Yurchenko, Olga; Shockey, Jay M; Gidda, Satinder K; Silver, Maxwell I; Chapman, Kent D; Mullen, Robert T; Dyer, John M

    2017-08-01

    The seeds of many nondomesticated plant species synthesize oils containing high amounts of a single unusual fatty acid, many of which have potential usage in industry. Despite the identification of enzymes for unusual oxidized fatty acid synthesis, the production of these fatty acids in engineered seeds remains low and is often hampered by their inefficient exclusion from phospholipids. Recent studies have established the feasibility of increasing triacylglycerol content in plant leaves, which provides a novel approach for increasing energy density of biomass crops. Here, we determined whether the fatty acid composition of leaf oil could be engineered to accumulate unusual fatty acids. Eleostearic acid (ESA) is a conjugated fatty acid produced in seeds of the tung tree (Vernicia fordii) and has both industrial and nutritional end-uses. Arabidopsis thaliana lines with elevated leaf oil were first generated by transforming wild-type, cgi-58 or pxa1 mutants (the latter two of which contain mutations disrupting fatty acid breakdown) with the diacylglycerol acyltransferases (DGAT1 or DGAT2) and/or oleosin genes from tung. High-leaf-oil plant lines were then transformed with tung FADX, which encodes the fatty acid desaturase/conjugase responsible for ESA synthesis. Analysis of lipids in leaves revealed that ESA was efficiently excluded from phospholipids, and co-expression of tung FADX and DGAT2 promoted a synergistic increase in leaf oil content and ESA accumulation. Taken together, these results provide a new approach for increasing leaf oil content that is coupled with accumulation of unusual fatty acids. Implications for production of biofuels, bioproducts, and plant-pest interactions are discussed. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  1. Conjugated fatty acid synthesis: residues 111 and 115 influence product partitioning of Momordica charantia conjugase.

    Science.gov (United States)

    Rawat, Richa; Yu, Xiao-Hong; Sweet, Marie; Shanklin, John

    2012-05-11

    Conjugated linolenic acids (CLNs), 18:3 Δ(9,11,13), lack the methylene groups found between the double bonds of linolenic acid (18:3 Δ(9,12,15)). CLNs are produced by conjugase enzymes that are homologs of the oleate desaturases FAD2. The goal of this study was to map the domain(s) within the Momordica charantia conjugase (FADX) responsible for CLN formation. To achieve this, a series of Momordica FADX-Arabidopsis FAD2 chimeras were expressed in the Arabidopsis fad3fae1 mutant, and the transformed seeds were analyzed for the accumulation of CLN. These experiments identified helix 2 and the first histidine box as a determinant of conjugase product partitioning into punicic acid (18:3 Δ(9cis,11trans,13cis)) or α-eleostearic acid (18:3 Δ(9cis,11trans,13trans)). This was confirmed by analysis of a FADX mutant containing six substitutions in which the sequence of helix 2 and first histidine box was converted to that of FAD2. Each of the six FAD2 substitutions was individually converted back to the FADX equivalent identifying residues 111 and 115, adjacent to the first histidine box, as key determinants of conjugase product partitioning. Additionally, expression of FADX G111V and FADX G111V/D115E resulted in an approximate doubling of eleostearic acid accumulation to 20.4% and 21.2%, respectively, compared with 9.9% upon expression of the native Momordica FADX. Like the Momordica conjugase, FADX G111V and FADX D115E produced predominantly α-eleostearic acid and little punicic acid, but the FADX G111V/D115E double mutant produced approximately equal amounts of α-eleostearic acid and its isomer, punicic acid, implicating an interactive effect of residues 111 and 115 in punicic acid formation.

  2. Ultrastructural changes in the isolated rat kidney induced by conjugated bilirubin and bile acids.

    Science.gov (United States)

    Gollan, J L; Billing, B H; Huang, S N

    1976-10-01

    The effects of bilirubin and bile acids on the ultrastructure of proximal renal tubules have been studied using an isolated rat kidney preparation, perfused with a protein-free dextran medium. Control kidneys perfused for 1 h had a normal glomerular filtration rate and effective renal plasma flow; the ultrastructure of proximal tubular cells was well preserved, with normal mitochondria, nuclear and plasma membranes, and microvilli of the brush border. When conjugated bilirubin, prepared from human hepatic bile, was added to the perfusion medium (5-0-7-5 mg/100 ml), marked alterations were observed in some cells, particularly with regard to the mitochondria and plasma membranes. These changes were greatly diminished by the inclusion of bovine albumin in the medium, indicating that the unbound fraction was primarily responsible for the tubular damage. The addition of taurocholate (450 muM), taurochenodeoxycholate (550 muM) or taurolithocholate (250 muM, bound to albumin) also produced plasma membrane changes, but only slight abnormalities were seen in the mitochondria and other structures. These ultrastructural observations support the concept that the elevated plasma levels of conjugated bilirubin and to a lesser extent bile acids are related to the renal failure associated with obstructive jaundice.

  3. Safflower oil consumption does not increase plasma conjugated linoleic acid concentrations in humans.

    Science.gov (United States)

    Herbel, B K; McGuire, M K; McGuire, M A; Shultz, T D

    1998-02-01

    Conjugated linoleic acid (CLA) is a mixture of positional and geometric isomers of linoleic acid (LA) with conjugated double bonds. CLA has anticarcinogenic properties and has been identified in human tissues, dairy products, meats, and certain vegetable oils. A variety of animal products are good sources of CLA, but plant oils contain much less. However, plant oils are a rich source of LA, which may be isomerized to CLA by intestinal microorganisms in humans. To investigate the effect of triacylglycerol-esterified LA consumption on plasma concentrations of esterified CLA in total lipids, a dietary intervention (6 wk) was conducted with six men and six women. During the intervention period a salad dressing containing 21 g safflower oil providing 16 g LA/d was added to the subjects' daily diets. Three-day diet records and fasting blood were obtained initially and during dietary and postdietary intervention periods. Although LA intake increased significantly during the dietary intervention, plasma CLA concentrations were not affected. Plasma total cholesterol and LDL-cholesterol concentrations were significantly lower after addition of safflower oil to the diet. In summary, consumption of triacylglycerol-esterified LA in safflower oil did not increase plasma concentrations of esterified CLA in total lipids.

  4. Conjugated Linoleic Acid Stimulates Apoptosis in RH and Tehran Strains of Toxoplasma gondii, in Vitro.

    Directory of Open Access Journals (Sweden)

    Jebreil Shamseddin

    2015-06-01

    Full Text Available The aim of this study was to evaluate the effects of conjugated linoleic acid (CLA on apoptosis of tachyzoites of T. gondii, RH strain (type I and the cyst-forming Tehran strain (type II in vitro.Toxoplasma strains were injected into the peritoneal cavity of BALB/c mice. The Tehran strain forms cysts in the brain of mice. Bradyzoites within the cysts are reactivated to proliferative tachyzoites, by dexamethasone. Tachyzoites were aspirated from the peritoneum of infected mice, and the percentage of viable parasites was estimated with trypan blue staining. Tachyzoites were inoculated into HeLa cells cultivated in DMEM medium. Different concentrations of CLA were evaluated on T. gondii in HeLa cells by the tetrazolium (MTT colorimetric assay. Differentiation between apoptosis and cell death was determined by flow cytometry using Annexin V and propidium iodide (PI double staining. The statistical analysis performed by GraphPad Prism version 6.00.CLA induces apoptosis in virulent (RH and avirulent (Tehran strains of T. gondii. The results of MTT indicated that CLA could decrease the proliferation of tachyzoites of both strains in HeLa cells.Conjugated linoleic acid has anti-toxoplasmacidal activity on tachyzoites of T. gondii. Therefore, we recommended further studies on this component in order to achieve a new drug against the parasite.

  5. Amino Acid Conjugated Anthraquinones from the Marine-Derived Fungus Penicillium sp. SCSIO sof101.

    Science.gov (United States)

    Luo, Minghe; Cui, Zhaomeng; Huang, Hongbo; Song, Xianqin; Sun, Aijun; Dang, Yongjun; Lu, Laichun; Ju, Jianhua

    2017-05-26

    Emodacidamides A-H (1-8), natural products featuring anthraquinone-amino acid conjugates, have been isolated from a marine-derived fungus, Penicillium sp. SCSIO sof101, together with known anthraquinones 9 and 10. The planar structures of 1-8 were elucidated using a combination of NMR spectroscopy and mass spectrometry. The absolute configurations of the amino acid residues were confirmed using Marfey's method and chiral-phase HPLC analyses. Additionally, isolates were evaluated for possible immunomodulatory and cytotoxic activities. Emodacidamides A (1), C (3), D (4), and E (5) inhibited interleukin-2 secretion from Jurkat cells with IC 50 values of 4.1, 5.1, 12, and 5.4 μM, respectively.

  6. Conjugates of 1'-Aminoferrocene-1-carboxylic Acid and Proline: Synthesis, Conformational Analysis and Biological Evaluation

    Directory of Open Access Journals (Sweden)

    Monika Kovačević

    2014-08-01

    Full Text Available Our previous studies showed that alteration of dipeptides Y-Fca-Ala-OMe (III into Y-Ala-Fca-OMe (IV (Y = Ac, Boc; Fca = 1'-aminoferrocene-1-carboxylic acid significantly influenced their conformational space. The novel bioconjugates Y-Fca-Pro-OMe (1, Y = Ac; 2, Y = Boc and Y-Pro-Fca-OMe (3, Y = Boc; 4, Y = Ac have been prepared in order to investigate the influence of proline, a well-known turn-inducer, on the conformational properties of small organometallic peptides with an exchanged constituent amino acid sequences. For this purpose, peptides 1–4 were subjected to detailed spectroscopic analysis (IR, NMR, CD spectroscopy in solution. The conformation of peptide 3 in the solid state was determined. Furthermore, the ability of the prepared conjugates to inhibit the growth of estrogen receptor-responsive MCF-7 mammary carcinoma cells and HeLa cervical carcinoma cells was tested.

  7. Analysis of conjugated linoleic acid and trans 18:1 isomers in synthetic and animal products.

    Science.gov (United States)

    Kramer, John K G; Cruz-Hernandez, Cristina; Deng, Zeyuan; Zhou, Jianqiang; Jahreis, Gerhard; Dugan, Michael E R

    2004-06-01

    The chemistry of conjugated fatty acids, specifically octadecadienoic acids (18:2; commonly referred to as conjugated linoleic acid, or CLA), has provided many challenges to lipid analysts because of their unique physical properties and the many possible positional and geometric isomers. After the acid-labile properties of CLAs during analytic procedures were overcome, it became evident that natural products, specifically dairy fats, contain one dominant (c9,t11-CLA), 3 intermediate (t7,c9-, t9,c11-, and t11,c13-CLA), and up to 20 more minor CLA isomers. The best analytic techniques to date include a combination of gas chromatography that uses 100-m highly polar capillary columns, silver ion-HPLC, and a combination of silver ion-thin-layer chromatography and gas chromatography to analyze the CLA and trans 18:1 isomers, because some of them serve as precursors of CLA in biological systems. These analytic techniques have assisted commercial suppliers to prepare pure CLA isomers and have permitted the evaluation of individual CLA isomers for their nutritional and biological activity in animal and human systems. It is increasingly evident that different CLA isomers have distinctly different physiologic and biochemical properties. These techniques are essential to evaluate dairy fats for their CLA content, to design experimental diets to increase the amount of CLA in dairy fats, and to determine the CLA profile in these CLA-enriched dairy fats. These improved techniques are used to evaluate the CLA profile in pork products from pigs fed different commercial CLA mixtures.

  8. Effects of clofibric acid on the biliary excretion of benoxaprofen glucuronide and taurine conjugate in rats.

    Science.gov (United States)

    Okada, K; Kanoh, H; Mohri, K

    2011-10-01

    Benoxaprofen (BOP) is a 2-methyl propionic acid derivative with anti-inflammatory activity. BOP has an asymmetric carbon, and receives chiral inversion from R to S in vivo. BOP is metabolized to glucuronide (BOP-G) and taurine conjugate (BOP-T). The configuration of BOP-G is mainly S, and that of BOP-T is R. Chiral inversion of R to S of the propionic acid moiety and amino acid conjugation of carboxyl compounds proceed via an acyl CoA intermediate. It is known that fibrates, used in hyperlipidemia, induce acyl CoA synthetase and increase CoA concentration. We administered racemic BOP (10 mg/kg body weight) to rats (CFA+) pre-administered clofibric acid (CFA, 280 mg/kg/day), and studied BOP, BOP-G, and BOP-T enantiomer concentrations in plasma and bile up to 12 h after administration. The findings were compared with those in rats (CFA-) that had not received CFA. Furthermore, we studied the amounts of BOP-G enantiomer produced by glucuronidation in vitro using microsomes pretreated with CFA. The amounts of (S)-BOP-G in CFA+ rats were 2.7-fold larger than that in CFA- rats. Although (R)-BOP-T was excreted in CFA- rats, BOP-T could not be detected in CFA+ rats. Plasma clearance values of racemic BOP and (S)-BOP in CFA+ rats were 5-fold and 6-fold larger than those in CFA- rats, respectively. (S)-BOP-G formation activities were higher than (R)-BOP-G formation activities in both CFA+and CFA- microsomes. These findings suggest that CFA increases biliary excretion of (S)-BOP-G and facilitates plasma elimination of BOP, and further suggests that CFA predominantly induces chiral inversion to S rather than metabolic reaction to (R)-BOP-T, resulting in an increase of (S)-BOP-G.

  9. Investigations into the choice of immunogen, ligand, antiserum and assay conditions for the radioimmunoassay of conjugated cholic acid

    Energy Technology Data Exchange (ETDEWEB)

    Beckett, G J; Percy-Robb, I W [Royal Infirmary, Edinburgh (UK); Hunter, W M [Medical Research Council, Edinburgh (UK)

    1978-09-01

    Investigations into the choice of immunogen, ligand, antiserum and assay conditions for the radioimmunoassay of conjugated cholic acid have been performed with a view to producing optimal assay conditions. Cholic acid-BSA was found to be the best immunogen to produce antibodies to conjugated cholic acid and the response was of an IgG type. Incorporating a spacer (hexanoic acid) between hapten and carrier protein resulted in a decrease in antiserum titre. Optimal conditions for the assay were found using (/sup 125/I)histamine-glycocholic acid as ligand with a dilution of antiserum to produce 60% binding of ligand and a pH of 7.4. Using these assay conditions no serum effects were found; extraction of serum prior to assay was therefore unnecessary. The assay was sensitive enough to detect post-prandial increases in serum bile acid concentrations following a liquid test meal; no increase was observed throughout the same time period in a fasting control.

  10. Phenylpropanoid profiling reveals a class of hydroxycinnamoyl glucaric acid conjugates in Isatis tinctoria leaves.

    Science.gov (United States)

    Nguyen, Thi-Kieu-Oanh; Jamali, Arash; Grand, Eric; Morreel, Kris; Marcelo, Paulo; Gontier, Eric; Dauwe, Rebecca

    2017-12-01

    The brassicaceous herb, Isatis tinctoria, is an ancient medicinal plant whose rosette leaf extracts have anti-inflammatory and anti-allergic activity. Brassicaceae are known to accumulate a variety of phenylpropanoids in their rosette leaves acting as antioxidants and a UV-B shield, and these compounds often have pharmacological potential. Nevertheless, knowledge about the phenylpropanoid content of I. tinctoria leaves remains limited to the characterization of a number of flavonoids. In this research, we profiled the methanol extracts of I. tinctoria fresh leaf extracts by liquid chromatography - mass spectrometry (LC-MS) and focused on the phenylpropanoid derivatives. We report the structural characterization of 99 compounds including 18 flavonoids, 21 mono- or oligolignols, 2 benzenoids, and a wide spectrum of 58 hydroxycinnamic acid esters. Besides the sinapate esters of malate, glucose and gentiobiose, which are typical of brassicaceous plants, these conjugates comprised a large variety of glucaric acid esters that have not previously been reported in plants. Feeding with 13 C 6 -glucaric acid showed that glucaric acid is an acyl acceptor of an as yet unknown acyltransferase activity in I. tinctoria rosette leaves. The large amount of hydroxycinnamic acid derivatives changes radically our view of the woad metabolite profile and potentially contributes to the pharmacological activity of I. tinctoria leaf extracts. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Improved cellular uptake of antisense Peptide nucleic acids by conjugation to a cell-penetrating Peptide and a lipid domain

    DEFF Research Database (Denmark)

    Shiraishi, Takehiko; Nielsen, Peter E

    2011-01-01

    based on a splicing correction of a mutated luciferase gene in HeLa pLuc705 cells by targeting antisense oligonucleotides to a cryptic splice site. Further improvement in the delivery of CatLip-PNA conjugates is achieved by using auxiliary agents/treatments (e.g., chloroquine, calcium ions......Unaided cellular uptake of RNA interference agents such as antisense oligonucleotides and siRNA is extremely poor, and in vivo bioavailability is also limited. Thus, effective delivery strategies for such potential drugs are in high demand. Recently, a novel approach using a class of short cationic....... We have found, however, that this low -bioavailability can be significantly improved by chemical conjugation to a lipid domain ("Lip," such as a fatty acid), thereby creating "CatLip"-conjugates. The cellular uptake of these conjugates is conveniently evaluated using a sensitive cellular assay system...

  12. In Vitro Investigation of Self-Assembled Nanoparticles Based on Hyaluronic Acid-Deoxycholic Acid Conjugates for Controlled Release Doxorubicin: Effect of Degree of Substitution of Deoxycholic Acid

    Directory of Open Access Journals (Sweden)

    Wen-Hao Wei

    2015-03-01

    Full Text Available Self-assembled nanoparticles based on a hyaluronic acid-deoxycholic acid (HD chemical conjugate with different degree of substitution (DS of deoxycholic acid (DOCA were prepared. The degree of substitution (DS was determined by titration method. The nanoparticles were loaded with doxorubicin (DOX as the model drug. The human cervical cancer (HeLa cell line was utilized for in vitro studies and cell cytotoxicity of DOX incorporated in the HD nanoparticles was accessed by the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. In addition, cellular uptake of fluorescently labeled nanoparticles was also investigated. An increase in the degree of deoxycholic acid substitution reduced the size of the nanoparticles and also enhanced their drug encapsulation efficiency (EE, which increased with the increase of DS. A higher degree of deoxycholic acid substitution also lead to a lower release rate and an initial burst release of doxorubicin from the nanoparticles. In summary, the degree of substitution allows the modulation of the particle size, drug encapsulation efficiency, drug release rate, and cell uptake efficiency of the nanoparticles. The herein developed hyaluronic acid-deoxycholic acid conjugates are a good candidate for drug delivery and could potentiate therapeutic formulations for doxorubicin–mediated cancer therapy.

  13. An efficient synthesis of tetramic acid derivatives with extended conjugation from L-Ascorbic Acid

    Directory of Open Access Journals (Sweden)

    Bisht Surendra S

    2006-12-01

    Full Text Available Abstract Background Tetramic acids with polyenyl substituents are an important class of compounds in medicinal chemistry. Both solid and solution phase syntheses of such molecules have been reported recently. Thiolactomycin, a clinical candidate for treatment of tuberculosis has led to further explorations in this class. We have recently developed an efficient synthesis of tetramic acids derivatives from L- ascorbic acid. In continuation of this work, we have synthesised dienyl tetramic acid derivatives. Results 5,6-O-Isopropylidene-ascorbic acid on reaction with DBU led to the formation of tetronolactonyl allyl alcohol, which on oxidation with pyridinium chlorochromate gave the respective tetranolactonyl allylic aldehydes. Wittig olefination followed by reaction of the resulting tetranolactonyl dienyl esters with different amines resulted in the respective 5-hydroxy lactams. Subsequent dehydration of the hydroxy lactams with p-toluene sulphonic acid afforded the dienyl tetramic acid derivatives. All reactions were performed at ambient temperature and the yields are good. Conclusion An efficient and practical method for the synthesis of dienyl tetramic acid derivatives from inexpensive and easily accessible ascorbic acid has been developed. The compounds bear structural similarities to the tetramic acid based polyenic antibiotics and thus this method offers a new and short route for the synthesis of tetramic acid derivatives of biological significance.

  14. Autoxidation of conjugated linoleic acid methyl ester in the presence of α-tocopherol: the hydroperoxide pathway

    OpenAIRE

    Pajunen, Taina

    2009-01-01

    The autoxidation of conjugated linoleic acid (CLA) is poorly understood in spite of increasing interest in the beneficial biological properties of CLA and growing consumption of CLA-rich foods. In this thesis, the autoxidation reactions of the two major CLA isomers, 9-cis,11-trans-octadecadienoic acid and 10-trans,12-cis-octadecadienoic acid, are investigated. The results contribute to an understanding of the early stages of the autoxidation of CLA methyl ester, and provide for the first time...

  15. Influence of dietary conjugated linoleic acid (CLA and L-Lysine on heavy pigs performances and meat quality

    Directory of Open Access Journals (Sweden)

    C. Corino

    2010-01-01

    Full Text Available Conjugated linoleic acid (CLA refers to a group of positional and geometric fatty acid isomers derived from linoleic acid. Dietary CLA supplementation has been shown to increase feed efficiency and may reduce body fat content in swine as recently reviewed by Corino et al., (2005. There was only one research conducted in heavy pig in which the authors did not observed any significant effect of dietary CLA on growth performances and lean tissue (Corino et al., 2003.

  16. Non-covalent conjugates of single-walled carbon nanotubes and folic acid for interaction with cells overexpressing folate receptors

    DEFF Research Database (Denmark)

    Castillo, John J.; Rindzevicius, Tomas; Novoa, Leidy V.

    2013-01-01

    We here present amethod to form a noncovalent conjugate of single-walled carbon nanotubes and folic acid aimed to interact with cells over-expressing folate receptors. The bonding was obtained without covalent chemical functionalization using a simple, rapid “one pot” synthesis method. The zeta...... a low toxicity of the conjugates in the THP-1 cells. The low toxicity and the cellular uptake of single-walled carbon nanotube–folic acid by cancer cells suggest their potential use in carbon nanotube-based drug delivery systems and in the diagnosis of cancer or tropical diseases such as leishmaniasis....

  17. Conjugated linoleic acid mitigates testosterone-related changes in body composition in male guinea pigs.

    Science.gov (United States)

    Yang, Susan Q; DeGuire, Jason R; Lavery, Paula; Mak, Ivy L; Weiler, Hope A; Santosa, Sylvia

    2016-05-01

    We hypothesize that conjugated linoleic acid (CLA) may be effective in preventing the changes in total and regional body composition and increases in interleukin (IL) 6 that occur as a result of hypogonadism. Male guinea pigs (n = 40, 70- to 72-week retired breeders) were block randomized by weight into 4 groups: (1) sham surgery (SHAM)/control (CTRL) diet, (2) SHAM/conjugated linoleic acid (CLA) diet (1%), (3) orchidectomy (ORX)/CTRL diet, and (4) ORX/CLA diet. Dual-energy x-ray absorptiometry scans were performed at baseline and week 16 to assess body composition. Serum IL-6 was analyzed using an enzyme-linked immune sorbent assay. Fatty acids (FAs) from visceral and subcutaneous adipose tissue were analyzed using gas chromatography. In ORX/CTRL guinea pigs, percent total body fat increased by 6.1%, and percent lean mass decreased by 6.7% over the 16-week treatment period, whereas no changes were observed for either parameter in ORX/CLA guinea pigs. Guinea pigs fed the CLA diet gained less percent total, upper, and lower body fat than those fed the CTRL diet regardless of surgical treatment. Regional adipose tissue FA composition was reflective of dietary FAs. Serum IL-6 concentrations were not different among groups. In this study, we observed that, in male guinea pigs, hypogonadism resulted in increased fat mass and decreased lean mass. In addition, CLA was effective in reducing gains in body fat and maintaining lean mass in both hypogonadal and intact guinea pigs. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. SN38 conjugated hyaluronic acid gold nanoparticles as a novel system against metastatic colon cancer cells.

    Science.gov (United States)

    Hosseinzadeh, Hosniyeh; Atyabi, Fatemeh; Varnamkhasti, Behrang Shiri; Hosseinzadeh, Reza; Ostad, Seyed Nasser; Ghahremani, Mohammad Hossein; Dinarvand, Rassoul

    2017-06-30

    Combination of chemotherapy and photothermal therapy has been proposed for better treatment of metastatic colon cancer. In this study SN38, a highly potent cytotoxic agent, was conjugated to negatively charged hyaluronic acid (HA), which was deposited on the surface of the positively charged gold nanoparticles via electrostatic interaction. The drug conjugation and its interaction with gold nanoparticles were verified by 1 H NMR and UV-vis spectroscopies, respectively. The prepared SN38-HA gold NPs are negatively charged spherical nanoparticles with an average size of 75±10nm. In vitro release study revealed that drug release in acidic conditions (pH 5.2) was faster than that in physiological pH. Red light emitting diode (LED, 630nm, 30mW) was used as a light source for photothermal experiments. The drug release in acidic conditions was increased up to 30% using red LED illumination (6min) in comparison with experiment carried out indark. The cytotoxicity study on MUC1 positive HT29, SW480 colon cancer cells and MUC1 negative CHO cells, showed higher toxicity of the nanoparticles on HT29 and SW480 cell lines compared to CHO cells. Confocal microscopy images along with flow cytometry analysis confirm the cytotoxicity results. The incubation time for reaching IC50 decreases from 48h to 24h by LED illumination after nanoparticle treatment. Migratory potential of the HT29 and SW480 cell lines was reduced by co-application of SN38-HA gold NPs and LED radiation. Also anti-proliferative study indicates that LED radiation has increased the cytotoxicity of the nanoparticles and this effect is remained up to 8days. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Production of Conjugated Linoleic and Conjugated α-Linolenic Acid in a Reconstituted Skim Milk-Based Medium by Bifidobacterial Strains Isolated from Human Breast Milk

    Directory of Open Access Journals (Sweden)

    María Antonia Villar-Tajadura

    2014-01-01

    Full Text Available Eight bifidobacterial strains isolated from human breast milk have been tested for their abilities to convert linoleic acid (LA and α-linolenic acid (LNA to conjugated linoleic acid (CLA and conjugated α-linolenic acid (CLNA, respectively. These bioactive lipids display important properties that may contribute to the maintenance and improvement human health. Three selected Bifidobacterium breve strains produced CLA from LA and CLNA from LNA in MRS (160–170 and 210–230 μg mL−1, resp. and, also, in reconstituted skim milk (75–95 and 210–244 μg mL−1, resp.. These bifidobacterial strains were also able to simultaneously produce both CLA (90–105 μg mL−1 and CLNA (290–320 μg mL−1 in reconstituted skim milk. Globally, our findings suggest that these bifidobacterial strains are potential candidates for the design of new fermented dairy products naturally containing very high concentrations of these bioactive lipids. To our knowledge, this is the first study describing CLNA production and coproduction of CLA and CLNA by Bifidobacterium breve strains isolated from human milk in reconstituted skim milk.

  20. Biocompatible Water Soluble Polyacrylic Acid Coated CdSe/Cu Quantum Dot Conjugates for Biomolecule Detection.

    Science.gov (United States)

    Gomaa, Ola M; Okasha, Aly; Hosni, Hany M; El-Hag Ali, Amr

    2018-01-01

    Biocompatible polyacrylic acid functionalized CdSe/Cu quantum dot conjugates were synthesized to be used for biomolecules detection. The study results demonstrate the conjugation of the 2.5-3 nm QD with gram negative bacteria with a low detection limit of 28 cfu/ml. The photoluminescence (PL) intensity was correlated to bacterial count, cellular proteins and exopolysaccharides in the tested samples. Confocal Scanning Laser Microscopy (CSLM) images showed significant QD uptake within the cells, both cytoplasm and DNA were the predominant targeted biomolecules, higher fluorescent uptake was shown in gram negative bacteria than that observed for gram positive bacteria. Moreover, PL showed that there was a distinction between live and dead cells as well as gram negative and gram positive cells. Cell viability was not affected even after 6 days (100% viability) rendering it a non-toxic QD. The method is simple and is performed in a single step within approximately 10 min as compared to multi-step protocols for classical microbial count or fluorescent dye staining. All the above results indicate that the CdSe/Cu-PAA QDs are suitable for biomolecule detection, bio-labeling and bioimaging applications.

  1. Conjugated linoleic acids as functional food: an insight into their health benefits

    Directory of Open Access Journals (Sweden)

    Benjamin Sailas

    2009-09-01

    Full Text Available Abstract This review evaluates the health benefits of the functional food, conjugated linoleic acids (CLA - a heterogeneous group of positional and geometric isomers of linoleic acid predominantly found in milk, milk products, meat and meat products of ruminants. During the past couple of decades, hundreds of reports - principally based on in vitro, microbial, animal, and of late clinical trials on humans - have been accumulating with varying biological activities of CLA isomers. These studies highlight that CLA, apart form the classical nuclear transcription factors-mediated mechanism of action, appear to exhibit a number of inter-dependent molecular signalling pathways accounting for their reported health benefits. Such benefits relate to anti-obesitic, anti-carcinogenic, anti-atherogenic, anti-diabetagenic, immunomodulatory, apoptotic and osteosynthetic effects. On the other hand, negative effects of CLA have been reported such as fatty liver and spleen, induction of colon carcinogenesis and hyperproinsulinaemia. As far as human consumption is concerned, a definite conclusion for CLA safety has not been reached yet. Parameters such as administration of the type of CLA isomer and/or their combination with other polyunsaturated fatty acids, mode of administration (eg., as free fatty acid or its triglyceride form, liquid or solid, daily dose and duration of consumption, gender, age, or ethnic and geographical backgrounds remain to be determined. Yet, it appears from trials so far conducted that CLA are functional food having prevailing beneficial health effects for humans.

  2. Enabling the Tablet Product Development of 5-Fluorocytosine by Conjugate Acid Base Cocrystals.

    Science.gov (United States)

    Perumalla, Sathyanarayana R; Paul, Shubhajit; Sun, Changquan C

    2016-06-01

    5-Fluorocytosine (FC) is a high-dose antifungal drug that challenges the development of a tablet product due to poor solid-state stability and tabletability. Using 2 pharmaceutically acceptable conjugate acid base (CAB) cocrystals of FC with HCl and acesulfame, we have developed commercially viable high loading FC tablets. The tablets were prepared by direct compression using nano-coated microcrystalline cellulose Avicel PH105 as a tablet binder, which provided both excellent tabletability and good flowability. Commercial manufacturability of formulations based on both CAB cocrystals was verified on a compaction simulator. The results from an expedited friability study were used to set the compaction force, which yielded tablets with sufficient mechanical strength and rapid tablet disintegration. This work demonstrates the potential value of CAB cocrystals in drug product development. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  3. Preliminary observations on the effects of milk fortification with conjugated linoleic acid in yogurt preparation

    Science.gov (United States)

    Salamon, R. V.; Albert, I.; András, C. D.; Csapó, J.; Ibănescu, C.

    2015-04-01

    The fortification and enrichment of food with health benefic natural or natural identical substances creating new functional foods became an important issue for food researchers and processors. However, often occurs that the obtained products (despite of their health benefic activity) cannot be marketed due to strange or accustomed taste and/or texture. The aim of the research was to elucidate the effect of conjugated linoleic acid (CLA) enrichment of raw milk on the rheological properties of the obtained yogurt. The results show that the values of the complex viscosity at 50 rad.s-1 (correlated with the thickness and sliminess of the food gel structures) of the CLA-enriched yogurt was the lowest among the studied samples, meaning the enriched yogurt is more creamy than the commercial products. These observations gave us the hope that, in this case, the texture of enriched product will not present any drawback related to consumer quality judgment.

  4. Anionic magnetite nanoparticle conjugated with pyrrolidinyl peptide nucleic acid for DNA base discrimination

    Energy Technology Data Exchange (ETDEWEB)

    Khadsai, Sudarat; Rutnakornpituk, Boonjira [Naresuan University, Department of Chemistry and Center of Excellence in Biomaterials, Faculty of Science (Thailand); Vilaivan, Tirayut [Chulalongkorn University, Department of Chemistry, Organic Synthesis Research Unit, Faculty of Science (Thailand); Nakkuntod, Maliwan [Naresuan University, Department of Biology, Faculty of Science (Thailand); Rutnakornpituk, Metha, E-mail: methar@nu.ac.th [Naresuan University, Department of Chemistry and Center of Excellence in Biomaterials, Faculty of Science (Thailand)

    2016-09-15

    Magnetite nanoparticles (MNPs) were surface modified with anionic poly(N-acryloyl glycine) (PNAG) and streptavidin for specific interaction with biotin-conjugated pyrrolidinyl peptide nucleic acid (PNA). Hydrodynamic size (D{sub h}) of PNAG-grafted MNPs varied from 334 to 496 nm depending on the loading ratio of the MNP to NAG in the reaction. UV–visible and fluorescence spectrophotometries were used to confirm the successful immobilization of streptavidin and PNA on the MNPs. About 291 pmol of the PNA/mg MNP was immobilized on the particle surface. The PNA-functionalized MNPs were effectively used as solid supports to differentiate between fully complementary and non-complementary/single-base mismatch DNA using the PNA probe. These novel anionic MNPs can be efficiently applicable for use as a magnetically guidable support for DNA base discrimination.Graphical Abstract.

  5. Anionic magnetite nanoparticle conjugated with pyrrolidinyl peptide nucleic acid for DNA base discrimination

    International Nuclear Information System (INIS)

    Khadsai, Sudarat; Rutnakornpituk, Boonjira; Vilaivan, Tirayut; Nakkuntod, Maliwan; Rutnakornpituk, Metha

    2016-01-01

    Magnetite nanoparticles (MNPs) were surface modified with anionic poly(N-acryloyl glycine) (PNAG) and streptavidin for specific interaction with biotin-conjugated pyrrolidinyl peptide nucleic acid (PNA). Hydrodynamic size (D h ) of PNAG-grafted MNPs varied from 334 to 496 nm depending on the loading ratio of the MNP to NAG in the reaction. UV–visible and fluorescence spectrophotometries were used to confirm the successful immobilization of streptavidin and PNA on the MNPs. About 291 pmol of the PNA/mg MNP was immobilized on the particle surface. The PNA-functionalized MNPs were effectively used as solid supports to differentiate between fully complementary and non-complementary/single-base mismatch DNA using the PNA probe. These novel anionic MNPs can be efficiently applicable for use as a magnetically guidable support for DNA base discrimination.Graphical Abstract

  6. Liver conversion of docosahexaenoic and arachidonic acids from their 18-carbon precursors in rats on a DHA-free but α-LNA-containing n-3 PUFA adequate diet.

    Science.gov (United States)

    Gao, Fei; Kim, Hyung-Wook; Igarashi, Miki; Kiesewetter, Dale; Chang, Lisa; Ma, Kaizong; Rapoport, Stanley I

    2011-01-01

    The long-chain polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA, 20:5n-3), docosahexaenoic acid (DHA, 22:6n-3), and arachidonic acid (AA, 20:4n-6), are critical for health. These PUFAs can be synthesized in liver from their plant-derived precursors, α-linolenic acid (α-LNA, 18:3n-3) and linoleic acid (LA, 18:2n-6). Vegetarians and vegans may have suboptimal long-chain n-3 PUFA status, and the extent of the conversion of α-LNA to EPA and DHA by the liver is debatable. We quantified liver conversion of DHA and other n-3 PUFAs from α-LNA in rats fed a DHA-free but α-LNA (n-3 PUFA) adequate diet, and compared results to conversion of LA to AA. [U-(13)C]LA or [U-(13)C]α-LNA was infused intravenously for 2h at a constant rate into unanesthetized rats fed a DHA-free α-LNA adequate diet, and published equations were used to calculate kinetic parameters. The conversion coefficient k(⁎) of DHA from α-LNA was much higher than for AA from LA (97.2×10(-3) vs. 10.6×10(-3)min(-1)), suggesting that liver elongation-desaturation is more selective for n-3 PUFA biosynthesis on a per molecule basis. The net daily secretion rate of DHA, 20.3μmol/day, exceeded the reported brain DHA consumption rate by 50-fold, suggesting that the liver can maintain brain DHA metabolism with an adequate dietary supply solely of α-LNA. This infusion method could be used in vegetarians or vegans to determine minimal daily requirements of EPA and DHA in humans. Published by Elsevier B.V.

  7. Enantioselective conjugate addition of silylketene acetals to beta-enamidomalonates. Synthesis of beta-amino acid derivatives.

    Science.gov (United States)

    Sibi, Mukund P; Chen, Jianxie

    2002-08-22

    [reaction: see text] Conjugate addition of silylketene acetals or enolsilanes to enamidomalonates proceeds with excellent chemical efficiency and good selectivity using Cu(OTf)2 and a chiral bisoxazoline. The effect of the Lewis acid, ligand, the N-acyl substituent, and the nucleophile on yield and selectivity for the addition product have been evaluated.

  8. Accurate pKa Calculation of the Conjugate Acids of Alkanolamines, Alkaloids and Nucleotide Bases by Quantum Chemical Methods

    NARCIS (Netherlands)

    Gangarapu, S.; Marcelis, A.T.M.; Zuilhof, H.

    2013-01-01

    The pKa of the conjugate acids of alkanolamines, neurotransmitters, alkaloid drugs and nucleotide bases are calculated with density functional methods (B3LYP, M08-HX and M11-L) and ab initio methods (SCS-MP2, G3). Implicit solvent effects are included with a conductor-like polarizable continuum

  9. The Adsorption Study of Aflatoxin B1 by Nanocellulose Conjugated with Aptamer in acidic, alkali, and Neutral Conditions

    Directory of Open Access Journals (Sweden)

    T Mirdehghan

    2016-03-01

    Full Text Available Introduction: Aflatoxin leads to liver cancer, its removal in the foodstuff is very important. The aim of this study is to investigate the adsorption of aflatoxin B1 by nanocellulose conjugated with aptamer in acidic, alkali, and neutral conditions. Methods: First, nanocellulose was synthesized by acid hydrolysis and then conjugated with aptamer by cross-linker. Then, serial concentrations of conjugated nanocellulose (0.6, 1.25, 2.5, 5, and 10 mg/mL were separately mixed with aflatoxin solution (1000µg/mL, and incubated at  37 °C for 0.5 h at pH of 1, 7, and 13. Then, the percentage of aflatoxin adsorption was measured at 340 nm.   Results: The decrease of pH led to increase of adsorption up to 40%. Statistically, there was significant difference between the quantity of adsorption at acidic condition and the quantity of adsorption at alkali and neutral conditions (P<0.05. Conclusion: Aflatoxin could be adsorbed by conjugated nanocellulose, and this power of adsorption is increased at acidic condition.

  10. Safety and Efficacy of Dextran-Rosmarinic Acid Conjugates as Innovative Polymeric Antioxidants in Skin Whitening: What Is the Evidence?

    Directory of Open Access Journals (Sweden)

    Ortensia I. Parisi

    2017-08-01

    Full Text Available Background: Melanins are high molecular weight pigments responsible for the mammalian skin and hair colour and play a key role in skin protection from UV radiation; however, their overproduction and excessive accumulation lead to pigmentation problems including melasma, freckles, uneven colouring, and age spots. Therefore, the modulation of melanin synthesis represents a critical issue in medicine and cosmetology. In the present study, an innovative polymeric antioxidant to be used as skin whitening agent is developed by the conjugation of dextran with rosmarinic acid. Methods: Dextran-rosmarinic acid conjugates (DEX-RA were synthesized in a one-pot method starting from Origanum vulgare aqueous leaf extract and dextran. The total polyphenol content and the antioxidant activity were assessed by Folin-Ciocalteau assay and 2,2-diphenyl-1-picrylhydrazyl radical (DPPH and bleaching tests, respectively. The efficacy of DEX-RA was evaluated by inhibition of tyrosinase activity, in vitro diffusion and stability studies and in vivo studies. The biocompatibility of the conjugates was investigated by 3-[4,5-Dimethylthiaoly]-2,5-diphenyltetrazoliumbromide (MTT and EPISKIN™ model. Results: Efficacy and safety studies confirmed the antioxidant and tyrosinase inhibitory activities and the biocompatibility of the synthesized conjugates. Conclusion: The polymeric conjugates, comparing to the free antioxidant, show a long-lasting efficacy combined to an enhanced stability resulting in an improved performance of the cosmetic formulations prepared using this innovative whitening agent as a bioactive ingredient.

  11. The synthesis of taurine-conjugated bile acids and bile acid sulfates labeled with {sup 14}C or {sup 3}H in the taurine moiety

    Energy Technology Data Exchange (ETDEWEB)

    Jie Zhang; Griffiths, W.J.; Sjoevall, Jan [Karolinska Inst., Medical Biochemistry and Biophysics Dept., Stockholm (Sweden)

    1997-02-01

    Studies of bile acid transport systems require radio-labeled taurine-conjugated bile acids with high specific activity. An established procedure was optimized to provide mild, fast, and effective conjugation of radio-labeled taurine with different types of bile acids, including those with labile 7{alpha}-hydroxy-3-oxo-{Delta}{sup 4} or 3{beta}, 7{alpha}-dihydroxy-{Delta}{sup 5} structures. Taurine labeled with {sup 14}C or {sup 3}H was reacted with excess bile acid anhydride formed from the tributylamine salt and ethylchloroformate (2/1 M/M) in aqueous dioxane for 15 min at room temperature. The yields were higher than 95% and less than 2% side products were formed. Bile acid sulfates were conjugated with {sup 14}C- or {sup 3}H-labeled taurine by using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline as the coupling reagent. The products were effectively purified by chromatography of the sodium salts on Sephadex LH-20. The yields of taurine-conjugated bile acid sulfates were 65-70%. (author).

  12. The synthesis of taurine-conjugated bile acids and bile acid sulfates labeled with 14C or 3H in the taurine moiety

    International Nuclear Information System (INIS)

    Jie Zhang; Griffiths, W.J.; Sjoevall, Jan

    1997-01-01

    Studies of bile acid transport systems require radio-labeled taurine-conjugated bile acids with high specific activity. An established procedure was optimized to provide mild, fast, and effective conjugation of radio-labeled taurine with different types of bile acids, including those with labile 7α-hydroxy-3-oxo-Δ 4 or 3β, 7α-dihydroxy-Δ 5 structures. Taurine labeled with 14 C or 3 H was reacted with excess bile acid anhydride formed from the tributylamine salt and ethylchloroformate (2/1 M/M) in aqueous dioxane for 15 min at room temperature. The yields were higher than 95% and less than 2% side products were formed. Bile acid sulfates were conjugated with 14 C- or 3 H-labeled taurine by using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline as the coupling reagent. The products were effectively purified by chromatography of the sodium salts on Sephadex LH-20. The yields of taurine-conjugated bile acid sulfates were 65-70%. (author)

  13. Conjugated linoleic acid or omega 3 fatty acids increase mitochondrial biosynthesis and metabolism in skeletal muscle cells

    Directory of Open Access Journals (Sweden)

    Vaughan Roger A

    2012-10-01

    Full Text Available Abstract Background Polyunsaturated fatty acids are popular dietary supplements advertised to contribute to weight loss by increasing fat metabolism in liver, but the effects on overall muscle metabolism are less established. We evaluated the effects of conjugated linoleic acid (CLA or combination omega 3 on metabolic characteristics in muscle cells. Methods Human rhabdomyosarcoma cells were treated with either DMSO control, or CLA or combination omega 3 for 24 or 48 hours. RNA was determined using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR. Mitochondrial content was determined using flow cytometry and immunohistochemistry. Metabolism was quantified by measuring extracellular acidification and oxygen consumption rates. Results Omega 3 significantly induced metabolic genes as well as oxidative metabolism (oxygen consumption, glycolytic capacity (extracellular acidification, and metabolic rate compared with control. Both treatments significantly increased mitochondrial content. Conclusion Omega 3 fatty acids appear to enhance glycolytic, oxidative, and total metabolism. Moreover, both omega 3 and CLA treatment significantly increase mitochondrial content compared with control.

  14. Nature of the elements transporting long-chain fatty acids through the red cell membrane

    DEFF Research Database (Denmark)

    Bojesen, Inge Norby; Bojesen, Eigil

    1998-01-01

    Docosahexaenoic acid, linoleic acid, red cell membrane, transporting elements, transport kinetics, fatty acid transport......Docosahexaenoic acid, linoleic acid, red cell membrane, transporting elements, transport kinetics, fatty acid transport...

  15. Docosahexaenoic Acid Induces Cell Death in Human Non-Small Cell Lung Cancer Cells by Repressing mTOR via AMPK Activation and PI3K/Akt Inhibition

    Directory of Open Access Journals (Sweden)

    Nayeong Kim

    2015-01-01

    Full Text Available The anticancer properties and mechanism of action of omega-3 polyunsaturated fatty acids (ω3-PUFAs have been demonstrated in several cancers; however, the mechanism in lung cancer remains unclear. Here, we show that docosahexaenoic acid (DHA, a ω3-PUFA, induced apoptosis and autophagy in non-small cell lung cancer (NSCLC cells. DHA-induced cell death was accompanied by AMP-activated protein kinase (AMPK activation and inactivated phosphatidylinositol 3-kinase (PI3K/Akt/mammalian target of rapamycin (mTOR signaling. Knocking down AMPK and overexpressing Akt increased mTOR activity and attenuated DHA-induced cell death, suggesting that DHA induces cell death via AMPK- and Akt-regulated mTOR inactivation. This was confirmed in Fat-1 transgenic mice, which produce ω3-PUFAs. Lewis lung cancer (LLC tumor cells implanted into Fat-1 mice showed slower growth, lower phospho-Akt levels, and higher levels of apoptosis and autophagy than cells implanted into wild-type mice. Taken together, these data suggest that DHA-induced apoptosis and autophagy in NSCLC cells are associated with AMPK activation and PI3K/Akt inhibition, which in turn lead to suppression of mTOR; thus ω3-PUFAs may be utilized as potential therapeutic agents for NSCLC treatment.

  16. Total Synthesis of Four Stereoisomers of (4Z,7Z,10Z,12E,16Z,18E)-14,20-Dihydroxy-4,7,10,12,16,18-docosahexaenoic Acid and Their Anti-inflammatory Activities.

    Science.gov (United States)

    Goto, Tomomi; Urabe, Daisuke; Masuda, Koji; Isobe, Yosuke; Arita, Makoto; Inoue, Masayuki

    2015-08-07

    A novel anti-inflammatory lipid mediator, (4Z,7Z,10Z,12E,14S,16Z,18E,20R)-14,20-dihydroxy-4,7,10,12,16,18-docosahexaenoic acid (1aa), and its three C14,C20 stereoisomers (1ab,ba,bb) were synthesized in a convergent fashion. The carbon backbone of the target compounds was assembled from seven simple fragments by employing two Sonogashira coupling and three SN2 alkynylation reactions. The thus constructed four internal alkynes were chemoselectively reduced to the corresponding (Z)-alkenes by applying a newly developed stepwise protocol: (i) hydrogenation of the three alkynes using Lindlar catalyst and (ii) formation of the dicobalt hexacarbonyl complex from the remaining alkyne and subsequent reductive decomplexation. The synthetic preparation of the stereochemically defined four isomers 1aa,ab,ba,bb permitted determination of the absolute structure of the isolated natural product to be 1aa. Biological testing of the four synthetic 14,20-dihydroxydocosahexaenoic acids disclosed similar anti-inflammatory activities of the non-natural isomers (1ab,ba,bb) and the natural form (1aa).

  17. Identification of glucuronides as in vivo liver conjugates of seven cannabinoids and some of their hydroxy and acid metabolites.

    Science.gov (United States)

    Harvey, D J; Martin, B R; Paton, W D

    1977-02-01

    Glucuronide conjugates of cannabidiol (CBD), 7-hydroxy-CBD, propyl-CBD, cannabinol (CBN), 7-hydroxy-CBN, CBN-7-oic acid, propyl CBN and cannabichromene have been identified as major metabolites of CBD, CBN and their propyl homologues and of cannabichromene in mouse liver. Trace amounts of the glucuronide conjugates of delta1- and delta1(6)-tetrahydrocannabinol (THC) were also detected. Identification was made by combined gas-liquid chromatographic and mass spectrometric studies of the trimethylsilyl (TMS), d9-TMS and methyl ester-TMS derivatives of the glucuronides and the TMS derivatives of the product of the reduction of the metabolites with lithium aluminium deuteride.

  18. Supplemental safflower oil affects the fatty acid profile, including conjugated linoleic acid, of lamb.

    Science.gov (United States)

    Boles, J A; Kott, R W; Hatfield, P G; Bergman, J W; Flynn, C R

    2005-09-01

    The objective of this study was to determine whether increasing levels of dietary safflower oil would alter unsaturated fat (especially CLA) and tocopherol content of lamb, animal performance, carcass characteristics, or color stability of lamb muscle tissue. Targhee x Rambouillet wethers (n = 60) were assigned to one of three diets (four pens per treatment with five lambs per pen) in a completely random design. Diets were formulated with supplemental safflower oil at 0 (control), 3, or 6% (as-fed basis) of the diet. Diets containing approximately 80% concentrate and 20% roughage were formulated, on a DM basis, to be isocaloric and isonitrogenous and to meet or exceed NRC requirements for Ca, P, and other nutrients. A subsample of 12 wethers per treatment was selected based on average BW (54 kg) and slaughtered. Carcass data (LM area, fat thickness, and internal fat content) and wholesale cut weight (leg, loin, rack, shoulder, breast, and foreshank), along with fatty acid, tocopherol, and color analysis, were determined on each carcass. The LM and infraspinatus were sampled for fatty acid profile. Increasing safflower oil supplementation from 0 to 3 or 6% increased the proportion of linoleic acid in the diet from 49.93 to 55.32 to 62.38%, respectively, whereas the percentage of oleic acid decreased from 27.94 to 23.80 to 20.73%, respectively. The percentage of oil in the diet did not (P > or = 0.11) alter the growth and carcass characteristics of lambs, nor did it alter the tocopherol content or color stability of meat. Increasing levels of safflower oil in lamb diets decreased (P safflower oil, up to 6% of the diet, resulted in increasing levels of unsaturated fatty acids and CLA in the lean tissue, without adversely affecting growth performance, carcass characteristics, or color stability of lamb.

  19. Characterization and stability analysis of zinc oxide nanoencapsulated conjugated linoleic acid.

    Science.gov (United States)

    Choy, Jin-Ho; Shin, Jiwon; Lim, Seung-Yong; Oh, Jae-Min; Oh, Mi-Hwa; Oh, Sangsuk

    2010-08-01

    Nanoencapsulation technology has a diverse range of applications, including drug-delivery systems (DDS) and cosmetic and chemical carriers, because it can deliver various bio- and organic-molecules and improve their stabilities. Conjugated linoleic acid (CLA) has health benefits, including being an anticancer agent, but it decreases flavor due to volatiles from oxidation. To improve the stability of CLA for food applications, nanoencapsulated CLA was synthesized for use in zinc basic salt (ZBS) and characterized by powder X-ray diffractometry, thermogravimetric analysis (TGA), elemental CHN analysis, inductively coupled plasma (ICP) analysis, UV/VIS spectroscopy, and FTIR spectroscopy. The thermal stability of nanoencapsulated CLA at 180 degrees C, a temperature similar to that used in cooking, was analyzed by gas chromatography. The gallery height of nanoencapsulated CLA was determined to be approximately 26 A through powder X-ray diffractometry; therefore, the CLA molecules were closely packed with zig-zag form between the intracrystalline spaces of nano particles. Elemental CHN analysis and ICP data determined the chemical composition of nanoencapsulated CLA to be Zn(4.86)(OH)(8.78)(CLA)(0.94). By TGA, it was determined about 45% (wt/wt) of weight loss corresponded to CLA, which is good agreement with the 42.13% (wt/wt) determined from high-performance liquid chromatography (HPLC) and elemental CHN analysis. UV/VIS spectroscopy and Fourier-transformed infrared (FTIR) spectroscopy showed encapsulated CLA maintained a conjugated diene structure, supporting the presence of CLA. Nanoencapsulation improved the thermal stability of CLA by about 25%, compared to pristine CLA. Practical Application: This system can be used for protection of encapsulated negatively-charged food ingredients from thermal processing.

  20. Lactobionic acid-conjugated TPGS nanoparticles for enhancing therapeutic efficacy of etoposide against hepatocellular carcinoma

    Science.gov (United States)

    Tsend-Ayush, Altansukh; Zhu, Xiumei; Ding, Yu; Yao, Jianxu; Yin, Lifang; Zhou, Jianping; Yao, Jing

    2017-05-01

    Many effective anti-cancer drugs have limited use in hepatocellular carcinoma (HCC) therapy due to the drug resistance mechanisms in liver cells. In recent years, tumor-targeted drug delivery and the inhibition of drug-resistance-related mechanisms has become an integrated strategy for effectively combating chemo-resistant cancer. Herein, lactobionic acid-conjugated d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS-LA conjugate) has been developed as a potential asialoglycoprotein receptor (ASGPR)-targeted nanocarrier and an efficient inhibitor of P-glycoprotein (P-gp) to enhance etoposide (ETO) efficacy against HCC. The main properties of ETO-loaded TPGS-LA nanoparticles (NPs) were tested through in vitro and in vivo studies after being prepared using the nanoprecipitation method and characterized by dynamic light scattering (DLS). According to the results, smaller (˜141.43 nm), positively charged ETO-loaded TPGS-LA NPs were more suitable for providing efficient delivery to hepatoma cells by avoiding the clearance mechanisms. It was found that ETO-loaded TPGS-LA NPs were noticeably able to enhance the cytotoxicity of ETO in HepG2 cells. Besides this, markedly higher internalization by the ASGPR-overexpressed HepG2 cells and efficient accumulation at the tumor site in vivo were revealed in the TPGS-LA NP group. More importantly, animal studies confirmed that ETO-loaded TPGS-LA NPs achieved the highest therapeutic efficacy against HCC. Interestingly, ETO-loaded TPGS-LA NPs also exhibited a great inhibitory effect on P-gp compared to the ETO-loaded TPGS NPs. These results suggest that TPGS-LA NPs could be used as a potential ETO delivery system against HCC.

  1. A randomized, crossover, head-to-head comparison of eicosapentaenoic acid and docosahexaenoic acid supplementation to reduce inflammation markers in men and women: the Comparing EPA to DHA (ComparED) Study.

    Science.gov (United States)

    Allaire, Janie; Couture, Patrick; Leclerc, Myriam; Charest, Amélie; Marin, Johanne; Lépine, Marie-Claude; Talbot, Denis; Tchernof, André; Lamarche, Benoît

    2016-08-01

    To date, most studies on the anti-inflammatory effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in humans have used a mixture of the 2 fatty acids in various forms and proportions. We compared the effects of EPA supplementation with those of DHA supplementation (re-esterified triacylglycerol; 90% pure) on inflammation markers (primary outcome) and blood lipids (secondary outcome) in men and women at risk of cardiovascular disease. In a double-blind, randomized, crossover, controlled study, healthy men (n = 48) and women (n = 106) with abdominal obesity and low-grade systemic inflammation consumed 3 g/d of the following supplements for periods of 10 wk: 1) EPA (2.7 g/d), 2) DHA (2.7 g/d), and 3) corn oil as a control with each supplementation separated by a 9-wk washout period. Primary analyses assessed the difference in cardiometabolic outcomes between EPA and DHA. Supplementation with DHA compared with supplementation with EPA led to a greater reduction in interleukin-18 (IL-18) (-7.0% ± 2.8% compared with -0.5% ± 3.0%, respectively; P = 0.01) and a greater increase in adiponectin (3.1% ± 1.6% compared with -1.2% ± 1.7%, respectively; P DHA and EPA, changes in CRP (-7.9% ± 5.0% compared with -1.8% ± 6.5%, respectively; P = 0.25), IL-6 (-12.0% ± 7.0% compared with -13.4% ± 7.0%, respectively; P = 0.86), and tumor necrosis factor-α (-14.8% ± 5.1% compared with -7.6% ± 10.2%, respectively; P = 0.63) were NS. DHA compared with EPA led to more pronounced reductions in triglycerides (-13.3% ± 2.3% compared with -11.9% ± 2.2%, respectively; P = 0.005) and the cholesterol:HDL-cholesterol ratio (-2.5% ± 1.3% compared with 0.3% ± 1.1%, respectively; P = 0.006) and greater increases in HDL cholesterol (7.6% ± 1.4% compared with -0.7% ± 1.1%, respectively; P DHA compared with EPA was significant in men but not in women (P-treatment × sex interaction = 0.046). DHA is more effective than EPA in modulating specific markers of inflammation

  2. Fatty acid-amino acid conjugates are essential for systemic activation of salicylic acid-induced protein kinase and accumulation of jasmonic acid in Nicotiana attenuata.

    Science.gov (United States)

    Hettenhausen, Christian; Heinrich, Maria; Baldwin, Ian T; Wu, Jianqiang

    2014-11-28

    Herbivory induces the activation of mitogen-activated protein kinases (MAPKs), the accumulation of jasmonates and defensive metabolites in damaged leaves and in distal undamaged leaves. Previous studies mainly focused on individual responses and a limited number of systemic leaves, and more research is needed for a better understanding of how different plant parts respond to herbivory. In the wild tobacco Nicotiana attenuata, FACs (fatty acid-amino acid conjugates) in Manduca sexta oral secretions (OS) are the major elicitors that induce herbivory-specific signaling but their role in systemic signaling is largely unknown. Here, we show that simulated herbivory (adding M. sexta OS to fresh wounds) dramatically increased SIPK (salicylic acid-induced protein kinase) activity and jasmonic acid (JA) levels in damaged leaves and in certain (but not all) undamaged systemic leaves, whereas wounding alone had no detectable systemic effects; importantly, FACs and wounding are both required for activating these systemic responses. In contrast to the activation of SIPK and elevation of JA in specific systemic leaves, increases in the activity of an important anti-herbivore defense, trypsin proteinase inhibitor (TPI), were observed in all systemic leaves after simulated herbivory, suggesting that systemic TPI induction does not require SIPK activation and JA increases. Leaf ablation experiments demonstrated that within 10 minutes after simulated herbivory, a signal (or signals) was produced and transported out of the treated leaves, and subsequently activated systemic responses. Our results reveal that N. attenuata specifically recognizes herbivore-derived FACs in damaged leaves and rapidly send out a long-distance signal to phylotactically connected leaves to activate MAPK and JA signaling, and we propose that FACs that penetrated into wounds rapidly induce the production of another long-distance signal(s) which travels to all systemic leaves and activates TPI defense.

  3. Are carboxyl groups the most acidic sites in amino acids? Gas-phase acidities, photoelectron spectra, and computations on tyrosine, p-hydroxybenzoic acid, and their conjugate bases.

    Science.gov (United States)

    Tian, Zhixin; Wang, Xue-Bin; Wang, Lai-Sheng; Kass, Steven R

    2009-01-28

    Deprotonation of tyrosine in the gas phase was found to occur preferentially at the phenolic site, and the conjugate base consists of a 70:30 mixture of phenoxide and carboxylate anions at equilibrium. This result was established by developing a chemical probe for differentiating these two isomers, and the presence of both ions was confirmed by photoelectron spectroscopy. Equilibrium acidity measurements on tyrosine indicated that deltaG(acid)(o) = 332.5 +/- 1.5 kcal mol(-1) and deltaH(acid)(o) = 340.7 +/- 1.5 kcal mol(-1). Photoelectron spectra yielded adiabatic electron detachment energies of 2.70 +/- 0.05 and 3.55 +/- 0.10 eV for the phenoxide and carboxylate anions, respectively. The H/D exchange behavior of deprotonated tyrosine was examined using three different alcohols (CF3CH2OD, C6H5CH2OD, and CH3CH2OD), and incorporation of up to three deuterium atoms was observed. Two pathways are proposed to account for these results, and all of the experimental findings are supplemented with B3LYP/aug-cc-pVDZ and G3B3 calculations. In addition, it was found that electrospray ionization of tyrosine from a 3:1 (v/v) CH3OH/H2O solution using a commercial source produces a deprotonated [M-H]- anion with the gas-phase equilibrium composition rather than the structure of the ion that exists in aqueous media. Electrospray ionization from acetonitrile, however, leads largely to the liquid-phase (carboxylate) structure. A control molecule, p-hydroxybenzoic acid, was found to behave in a similar manner. Thus, the electrospray conditions that are employed for the analysis of a compound can alter the isomeric composition of the resulting anion.

  4. Orally administered conjugated linoleic acid ameliorates allergic dermatitis induced by repeated applications of oxazolone in mice.

    Science.gov (United States)

    Nakanishi, Tomonori; Tokunaga, Yuzo; Yamasaki, Masao; Erickson, Laurie; Kawahara, Satoshi

    2016-12-01

    Conjugated linoleic acid (CLA) is one of the constituents of animal products with possible health benefits such as anti-carcinogenic and anti-obesity effects. In this study, we investigated the immunomodulatory effects of CLA using a mouse model of allergic dermatitis. Mice were orally administered either a CLA mixture containing equal amounts of 9c, 11 t-CLA and 10 t, 12c-CLA, or high linoleic acid safflower oil, and allergic dermatitis was induced on the ear by repeated topical applications of oxazolone. Oral administration of the CLA mixture but not the high linoleic safflower oil attenuated the symptoms of allergic dermatitis in both ear weights and clinical scores. This effect was associated with decreased levels of ear interleukin-4 (IL-4) and plasma immunoglobulin E. The immunomodulatory effects of the CLA isomers were compared by an in vitro cytokine production assay. The results showed that 9c, 11 t-CLA, the most predominant isomer in animal products, significantly inhibited IL-4 and interferon-γ production from mouse splenocytes with similar potency to 10 t, 12c-CLA. These findings suggest that CLA, a constituent of animal products, has a potentially beneficial effect for amelioration of allergic dermatitis. © 2016 Japanese Society of Animal Science.

  5. Lecithin-Based Nano-emulsification Improves the Bioavailability of Conjugated Linoleic Acid.

    Science.gov (United States)

    Heo, Wan; Kim, Jun Ho; Pan, Jeong Hoon; Kim, Young Jun

    2016-02-17

    In this study, we investigated the effects of lecithin-based nano-emulsification on the heat stability and bioavailability of conjugated linoleic acid (CLA) in different free fatty acid (FFA) and triglyceride (TG) forms. CLA nano-emulsion in TG form exhibited a small droplet size (70-120 nm) compared to CLA nano-emulsion in FFA form (230-260 nm). Nano-emulsification protected CLA isomers in TG form, but not in free form, against thermal decomposition during the heat treatment. The in vitro bioavailability test using monolayers of Caco-2 human intestinal cells showed that nano-emulsification increased the cellular uptake of CLA in both FFA and TG forms. More importantly, a rat feeding study showed that CLA content in small intestinal tissues or plasma was higher when CLA was emulsified, indicating an enhanced oral bioavailability of CLA by nano-emulsification. These results provide important information for development of nano-emulsion-based delivery systems that improve thermal stability and bioavailability of CLA.

  6. Chemometric deconvolution of gas chromatographic unresolved conjugated linoleic acid isomers triplet in milk samples.

    Science.gov (United States)

    Blasko, Jaroslav; Kubinec, Róbert; Ostrovský, Ivan; Pavlíková, Eva; Krupcík, Ján; Soják, Ladislav

    2009-04-03

    A generally known problem of GC separation of trans-7;cis-9; cis-9,trans-11; and trans-8,cis-10 CLA (conjugated linoleic acid) isomers was studied by GC-MS on 100m capillary column coated with cyanopropyl silicone phase at isothermal column temperatures in a range of 140-170 degrees C. The resolution of these CLA isomers obtained at given conditions was not high enough for direct quantitative analysis, but it was, however, sufficient for the determination of their peak areas by commercial deconvolution software. Resolution factors of overlapped CLA isomers determined by the separation of a model CLA mixture prepared by mixing of a commercial CLA mixture and CLA isomer fraction obtained by the HPLC semi-preparative separation of milk fatty acids methyl esters were used to validate the deconvolution procedure. Developed deconvolution procedure allowed the determination of the content of studied CLA isomers in ewes' and cows' milk samples, where dominant isomer cis-9,trans-11 is eluted between two small isomers trans-7,cis-9 and trans-8,cis-10 (in the ratio up to 1:100).

  7. A review on effects of conjugated linoleic fatty acid (CLA) upon body composition and energetic metabolism.

    Science.gov (United States)

    Lehnen, Tatiana Ederich; da Silva, Marcondes Ramos; Camacho, Augusto; Marcadenti, Aline; Lehnen, Alexandre Machado

    2015-01-01

    Conjugated linoleic acid (CLA) is highly found in fats from ruminants and it appears to favorably modify the body composition and cardiometabolic risk factors. The capacity of CLA to reduce the body fat levels as well as its benefic actions on glycemic profile, atherosclerosis and cancer has already been proved in experimental models. Furthermore, CLA supplementation may modulate the immune function, help re-synthetize of glycogen and potentiate the bone mineralization. CLA supplementation also could increase the lipolysis and reduce the accumulation of fatty acids on the adipose tissue; the putative mechanisms involved may be its action in reducing the lipase lipoprotein activity and to increase the carnitine-palmitoil-transferase-1 (CAT-1) activity, its interaction with PPARγ, and to raise the expression of UCP-1. Although studies made in human have shown some benefits of CLA supplementation as the weight loss, the results are still discordant. Moreover, some have shown adverse effects, such as negative effects on glucose metabolism and lipid profile. The purpose of this article is to review the available data regarding the benefits of CLA on the energetic metabolism and body composition, emphasizing action mechanisms.

  8. Bioproduction of conjugated linoleic acid by probiotic bacteria occurs in vitro and in vivo in mice.

    Science.gov (United States)

    Ewaschuk, Julia B; Walker, John W; Diaz, Hugo; Madsen, Karen L

    2006-06-01

    Probiotics have been shown to reduce the incidence of colon cancer in animal models. The mechanisms responsible for this activity are poorly defined. Conjugated linoleic acids (CLA) are a group of isomers of linoleic acid (LA) possessing anti-inflammatory and anticarcinogenic properties, which can be produced from LA by certain bacterial strains. In this study, the ability of probiotic bacteria to exert anticarcinogenic effects through the production of CLA was assessed. Incubation of probiotic bacteria (VSL3, Lactobacillus acidophilus, L. bulgaricus, L. casei, L. plantarum, Bifidobacterium breve, B. infantis, B. longum, and Streptococcus thermophilus) in the presence of LA yielded CLA production as measured by gas chromatography. Conditioned medium, containing probiotic-produced CLA, reduced viability and induced apoptosis of HT-29 and Caco-2 cells, as assessed by MTT assay and DNA laddering, respectively. Western blotting demonstrated an increased expression of PPARgamma in cells treated with conditioned medium compared with LA alone. Incubation of murine feces with LA after administering VSL3 yielded 100-fold more CLA than feces collected prior to VSL3 feeding. This study supports a role for supplemental probiotics as a strategy both for attenuating inflammation and for preventing colon cancer.

  9. role of conjugated linoleic acid in the prevention of radiation hazard in male rats

    International Nuclear Information System (INIS)

    Hussien, E.M.; Osman, N.N.; Haggag, A.M.

    2009-01-01

    the objective of the present study was to examine the effect of conjugated linoleic acid (CLA) as a natural product in minimizing the radiation hazards. male rats were assigned to six groups each of 7 animals throughout six weeks, fed 1% CLA (wt/wt)added to commercial diet in the form of milk powder 182 g/kg diet. rats exposed to 6 Gy whole body gamma irradiation showed significant increase in total cholesterol (TC), low density lipoprotein cholesterol (LDL-C).triglycerides (TG), atherosclerosis index, total lipid (TL), phospholipids (ph-lipids), malondialdehyde (MDA), urea,creatinine, uric acid, calcium (Ca) and phosphorous levels associated with decrease in high density lipoprotein-cholesterol (HDL-C), activity of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), total antioxidant status, body weight, testes weight and testosterone both irradiated and non-irradiated milk powder administrated to irradiated rat groups minimized the radiation damage in the assayed parameters indicating its beneficial role as a promising antioxidant in scavenging free radicals and reactive oxygen species

  10. Influence of conjugated linoleic acid (CLA on intramuscular fatty acid composition in rabbit

    Directory of Open Access Journals (Sweden)

    C. Corino

    2010-01-01

    Full Text Available The impact of feeding CLA has been thoroughly investigated in pigs, and Thiel- Cooper et al. (2001, Ostrowska et al. (2003, Lo Fiego et al. (2004, found that CLA modifies lipid fatty acid profile, negatively affecting some nutritional lipid indexes. So far,much less attention has been paid to rabbits. Recently, Corino et al. (2003 have shown that supplementing rabbit diets with CLA has limited effect on the chemical composition of meat and at a high slaughter weight reduces intramuscular fat content. The present research has been carried out to evaluate the effect of dietary CLA supplementation on cis-9, trans-11 and trans-10,cis-12- C18:2 isomers content, and on fatty acid composition of rabbit intramuscular lipids.

  11. Calcium ions effectively enhance the effect of antisense peptide nucleic acids conjugated to cationic tat and oligoarginine peptides

    DEFF Research Database (Denmark)

    Shiraishi, Takehiko; Pankratova, Stanislava; Nielsen, Peter E

    2005-01-01

    Cell-penetrating peptides have been widely used to improve cellular delivery of a variety of proteins and antisense agents. However, recent studies indicate that such cationic peptides are predominantly entering cells via an endosomal pathway. We now show that the nuclear antisense effect in He......La cells of a variety of peptide nucleic acid (PNA) peptide conjugates is significantly enhanced by addition of 6 mM Ca(2+) (as well as by the lysosomotrophic agent chloroquine). In particular, the antisense activities of Tat(48-60) and heptaarginine-conjugated PNAs were increased 44-fold and 8.5-fold......, respectively. Evidence is presented that the mechanism involves endosomal release. The present results show that Ca(2+) can be used as an effective enhancer for in vitro cellular delivery of cationic peptide-conjugated PNA oligomers, and also emphasize the significance of the endosomal escape route...

  12. Radiosynthesis of N-¹¹C-Methyl-Taurine-Conjugated Bile Acids and Biodistribution Studies in Pigs by PET/CT.

    Science.gov (United States)

    Schacht, Anna Christina; Sørensen, Michael; Munk, Ole Lajord; Frisch, Kim

    2016-04-01

    During cholestasis, accumulation of conjugated bile acids may occur in the liver and lead to hepatocellular damage. Inspired by our recent development of N-(11)C-methyl-glycocholic acid-that is, (11)C-cholylsarcosine-a tracer for PET of the endogenous glycine conjugate of cholic acid, we report here a radiosynthesis of N-(11)C-methyl-taurine-conjugated bile acids and biodistribution studies in pigs by PET/CT. A radiosynthesis of N-(11)C-methyl-taurine-conjugated bile acids was developed and used to prepare N-(11)C-methyl-taurine conjugates derived from cholic, chenodeoxycholic, deoxycholic, ursodeoxycholic, and lithocholic acid. The lipophilicity of these new tracers was determined by reversed-phase thin-layer chromatography. The effect of lipophilicity and structure on the biodistribution was investigated in pigs by PET/CT using the tracers derived from cholic acid (3α-OH, 7α-OH, 12α-OH), ursodeoxycholic acid (3α-OH, 7β-OH), and lithocholic acid (3α-OH). The radiosyntheses of the N-(11)C-methyl-taurine-conjugated bile acids proceeded with radiochemical yields of 61% (decay-corrected) or greater and radiochemical purities greater than 99%. PET/CT in pigs revealed that the tracers were rapidly taken up by the liver and secreted into bile. There was no detectable radioactivity in urine. Significant reflux of N-(11)C-methyl-taurolithocholic acid into the stomach was observed. We have successfully developed a radiosynthesis of N-(11)C-methyl-taurine-conjugated bile acids. These tracers behave in a manner similar to endogenous taurine-conjugated bile acids in vivo and are thus promising for functional PET of patients with cholestatic diseases. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  13. Vectorization of agrochemicals: amino acid carriers are more efficient than sugar carriers to translocate phenylpyrrole conjugates in the Ricinus system.

    Science.gov (United States)

    Wu, Hanxiang; Marhadour, Sophie; Lei, Zhi-Wei; Yang, Wen; Marivingt-Mounir, Cécile; Bonnemain, Jean-Louis; Chollet, Jean-François

    2018-05-01

    Producing quality food in sufficient quantity while using less agrochemical inputs will be one of the great challenges of the twenty-first century. One way of achieving this goal is to greatly reduce the doses of plant protection compounds by improving the targeting of pests to eradicate. Therefore, we developed a vectorization strategy to confer phloem mobility to fenpiclonil, a contact fungicide from the phenylpyrrole family used as a model molecule. It consists in coupling the antifungal compound to an amino acid or a sugar, so that the resulting conjugates are handled by active nutrient transport systems. The method of click chemistry was used to synthesize three conjugates combining fenpiclonil to glucose or glutamic acid with a spacer containing a triazole ring. Systemicity tests with the Ricinus model have shown that the amino acid promoiety was clearly more favorable to phloem mobility than that of glucose. In addition, the transport of the amino acid conjugate is carrier mediated since the derivative of the L series was about five times more concentrated in the phloem sap than its counterpart of the D series. The systemicity of the L-derivative is pH dependent and almost completely inhibited by the protonophore carbonyl cyanide 3-chlorophenylhydrazone (CCCP). These data suggest that the phloem transport of the L-derivative is governed by a stereospecific amino acid carrier system energized by the proton motive force.

  14. In vitro synergistic efficacy of conjugated linoleic acid, oleic acid, safflower oil and taxol cytotoxicity on PC3 cells.

    Science.gov (United States)

    Kızılşahin, Sadi; Nalbantsoy, Ayşe; Yavaşoğlu, N Ülkü Karabay

    2015-01-01

    The aim of this study was to determine in vitro synergistic efficacy of conjugated linoleic acid (CLA), oleic acid (OLA), safflower oil and taxol (Tax) cytotoxicity on human prostate cancer (PC3) cell line. To determine synergistic efficacy of oil combinations, PC3 treated with different doses of compounds alone and combined with 10 μg/mL Tax. The MTT results indicated that OLA-Tax combinations exhibited cytotoxicity against PC3 at doses of 30 nM+10 μg-Tax, 15 nM+5 μg-Tax and 7.5 nM+2.5 μg-Tax. The treatment of OLA or Tax did not show significant inhibition on PC3, while OLA-Tax combinations showed effective cytotoxicity at treated doses. CLA-Tax combinations demonstrated the same effect on PC3 as combined form with 45.72% versus the alone form as 74.51% viability. Cytotoxic synergy between Tax, OLA and CLA shows enhanced cytotoxicity on PC3 which might be used in the therapy of prostate cancer.

  15. Comparative effects of conjugated linoleic acid (CLA) and linoleic acid (LA) on the oxidoreduction status in THP-1 macrophages.

    Science.gov (United States)

    Rybicka, Marta; Stachowska, Ewa; Gutowska, Izabela; Parczewski, Miłosz; Baśkiewicz, Magdalena; Machaliński, Bogusław; Boroń-Kaczmarska, Anna; Chlubek, Dariusz

    2011-04-27

    The aim of this study was to investigate the effect of conjugated linoleic acids (CLAs) on macrophage reactive oxygen species synthesis and the activity and expression of antioxidant enzymes, catalase (Cat), glutathione peroxidase (GPx), and superoxide dismutase (SOD). The macrophages were obtained from the THP-1 monocytic cell line. Cells were incubated with the addition of cis-9,trans-11 CLA or trans-10,cis-12 CLA or linoleic acid. Reactive oxygen species (ROS) formation was estimated by flow cytometry. Enzymes activity was measured spectrophotometrically. The antioxidant enzyme mRNA expression was estimated by real-time reverse transcriptase polymerase chain reaction (RT-PCR). Statistical analysis was based on nonparametric statistical tests [Friedman analysis of variation (ANOVA) and Wilcoxon signed-rank test]. cis-9,trans-11 CLA significantly increased the activity of Cat, while trans-10,cis-12 CLA notably influenced GPx activity. Both isomers significantly decreased mRNA expression for Cat. Only trans-10,cis-12 significantly influenced mRNA for SOD-2 expression. The CLAs activate processes of the ROS formation in macrophages. Adverse metabolic effects of each isomer action were observed.

  16. Enrichment of conjugated linoleic acid (CLA) in hen eggs and broiler chickens meat by lactic acid bacteria.

    Science.gov (United States)

    Herzallah, Saqer

    2013-01-01

    1. The aim of this work was to compare conjugated linoleic acid (CLA) concentrations in chickens supplemented with 4 American Tissue Culture Collection (ATCC) bacterial strains, Lactobacillus plantarum, Lactobacillus lactis, Lactobacillus casei and Lactobacillus fermentum, and 4 isolates of Lactobacillus reuteri from camel, cattle, sheep and goat rumen extracts. 2. Micro-organisms were grown anaerobically in MRS broth, and 10(6) CFU/ml of bacteria were administered orally to mixed-sex, 1-d-old broiler chickens weekly for 4 weeks and to 23-week-old layer hens weekly for 6 weeks. 3. The 4 strains were evaluated for their effects on synthesis of CLA in hen eggs and broiler meat cuts. 4. Administration of pure Lactobacillus and isolated L. reuteri strains from camel, cattle, goat and sheep led to significantly increased CLA concentrations of 0.2-1.2 mg/g of fat in eggs and 0.3-1.88 mg/g of fat in broiler chicken flesh homogenates of leg, thigh and breast. 5. These data demonstrate that lactic acid bacteria of animal origin (L. reuteri) significantly enhanced CLA synthesis in both eggs and broiler meat cuts.

  17. A randomized, placebo-controlled, double-blind trial of supplemental docosahexaenoic acid on cognitive processing speed and executive function in females of reproductive age with phenylketonuria: A pilot study☆, ☆☆

    Science.gov (United States)

    Yi, S.H.L.; Kable, J.A.; Evatt, M.L.; Singh, R.H.

    2014-01-01

    Low blood docosahexaenoic acid (DHA) is reported in patients with phenylketonuria (PKU); however, the functional implications in adolescents and adults are unknown. This pilot study investigated the effect of supplemental DHA on cognitive performance in 33 females with PKU ages 12–47 years. Participants were randomly assigned to receive DHA (10 mg/kg/day) or placebo for 4.5 months. Performance on cognitive processing speed and executive functioning tasks was evaluated at baseline and follow up. Intention-to-treat and per protocol analyses were performed. At follow up, biomarkers of DHA status were significantly higher in the DHA-supplemented group. Performance on the cognitive tasks and reported treatment-related adverse events did not differ. While no evidence of cognitive effect was seen, a larger sample size is needed to be conclusive, which may not be feasible in this population. Supplementation was a safe and effective way to increase biomarkers of DHA status (www.clinicaltrials.gov; Identifier: NCT00892554). PMID:22000478

  18. Fabrication and Protein Conjugation of Aligned Polypyrrole-Poly(L-lactic acid) Fibers Film with the Conductivity and Stability.

    Science.gov (United States)

    Qin, Jiabang; Huang, Zhongbing; Yin, Guangfu; Yang, Anneng; Han, Wei

    2016-03-01

    The conducting composite scaffold, including fiber-cores of aligned poly(L-lactic acid) (PLLA) and shell-layer of polypyrrole (PPy), was fabricated, and then bovine serum albumin (BSA) was conjugated on the PPy shell-layer. Aligned PLLA fibers (about 300 nm diameter) were obtained by electrospinning and rotating drum collection, and then coated by PPy nanoparticles (NPs, about 50 nm diameter) via chemical oxidation. The surface resistivity of PPy-PLLA fibers film were 0.971, 0.874 kΩ. cm at the fiber's vertical and parallel directions, respectively. The results of PPy-PLLA fibers film immersed in phosphate buffer saline for 8 d indicated that the fibers morphology and the film conductivity were not significantly changed, and the fluorescent images showed that FITC-labeled BSA (FITC-BSA) were successfully conjugated in the fibers film with carbodiimide chemistry, and the largest amount of FITC-BSA conjugated in the fibers film from 100 μg/mL proteins solution was 31.31 μg/cm2 due to lots of poly(glutamic acid) in surface-nanogrooves of the fibers surface. Under electrical stimulation of 100 mV, the fibers film was accompanied the release of all conjugated FITC-BSA with the detachment of some PPy NPs. These results suggested that PPy-PLLA fibers film would be potentially applied in the construction of degradable tissue engineering scaffold with protein factors, especially neurotrophic factors for nerve tissue repair.

  19. Use of a novel docosahexaenoic acid (DHA) formulation versus control in a neonatal porcine model of short bowel syndrome leads to greater intestinal absorption and higher systemic levels of DHA

    Science.gov (United States)

    Martin, Camilia R.; Stoll, Barbara; Cluette-Brown, Joanne; Akinkuotu, Adesola C.; Olutoye, Oluyinka O.; Gura, Kathleen M.; Singh, Pratibha; Zaman, Munir M.; Perillo, Michael C.; Puder, Mark; Freedman, Steven D.; Burrin, Doug

    2017-01-01

    Infants with short bowel syndrome (SBS) are at high risk for malabsorption, malnutrition, and failure to thrive. The objective of this study was to evaluate in a porcine model of SBS, the systemic absorption of a novel enteral Docosahexaenoic acid (DHA) formulation that forms micelles independent of bile salts (DHA-ALT®). We hypothesized that enteral delivery of DHA-ALT® would result in higher blood levels of DHA compared to a control DHA preparation due to improved intestinal absorption. SBS was induced in term piglets through a 75% mid-jejunoileal resection and the piglets randomized to either DHA-ALT® or control DHA formulation (N=5 per group) for 4 postoperative days. The median ± IQR difference in final versus starting weight was 696 ± 425g in the DHA-ALT® group compared to 132 ± 278g in the controls (p=.08). Within 12 hours, median ± IQR DHA and eicosapentaenoic acid plasma levels (mol%) were significantly higher in the DHA-ALT® vs. control group (4.1 ± 0.3 vs 2.5 ± 0.5, p=0.009; 0.7 ± 0.3 vs 0.2 ± 0.005, p=0.009, respectively). There were lower fecal losses of DHA and greater ileal tissue incorporation with DHA-ALT® versus the control. Morphometric analyses demonstrated an increase in proximal jejunum and distal ileum villus height in the DHA-ALT® group compared to controls (p=0.01). In a neonatal porcine model of SBS, enteral administration of a novel DHA preparation that forms micelles independent of bile salts resulted in increased fatty acid absorption, increased ileal tissue incorporation, and increased systemic levels of DHA. PMID:28385289

  20. Use of a novel docosahexaenoic acid formulation vs control in a neonatal porcine model of short bowel syndrome leads to greater intestinal absorption and higher systemic levels of DHA.

    Science.gov (United States)

    Martin, Camilia R; Stoll, Barbara; Cluette-Brown, Joanne; Akinkuotu, Adesola C; Olutoye, Oluyinka O; Gura, Kathleen M; Singh, Pratibha; Zaman, Munir M; Perillo, Michael C; Puder, Mark; Freedman, Steven D; Burrin, Doug

    2017-03-01

    Infants with short bowel syndrome (SBS) are at high risk for malabsorption, malnutrition, and failure to thrive. The objective of this study was to evaluate in a porcine model of SBS, the systemic absorption of a novel enteral Docosahexaenoic acid (DHA) formulation that forms micelles independent of bile salts (DHA-ALT®). We hypothesized that enteral delivery of DHA-ALT® would result in higher blood levels of DHA compared to a control DHA preparation due to improved intestinal absorption. SBS was induced in term piglets through a 75% mid-jejunoileal resection and the piglets randomized to either DHA-ALT® or control DHA formulation (N=5 per group) for 4 postoperative days. The median±IQR difference in final vs starting weight was 696±425 g in the DHA-ALT® group compared to 132±278 g in the controls (P=.08). Within 12 hours, median±IQR DHA and eicosapentaenoic acid plasma levels (mol%) were significantly higher in the DHA-ALT® vs control group (4.1±0.3 vs 2.5±0.5, P=.009; 0.7±0.3 vs 0.2±0.005, P=.009, respectively). There were lower fecal losses of DHA and greater ileal tissue incorporation with DHA-ALT® vs the control. Morphometric analyses demonstrated an increase in proximal jejunum and distal ileum villus height in the DHA-ALT® group compared to controls (P=.01). In a neonatal porcine model of SBS, enteral administration of a novel DHA preparation that forms micelles independent of bile salts resulted in increased fatty acid absorption, increased ileal tissue incorporation, and increased systemic levels of DHA. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Continuous gradient temperature Raman spectroscopy of the long chain polyunsaturated fatty acids docosapentaenoic (DPA, 22:5n-6) and docosahexaenoic (DHA; 22:6n-3) from -100 to 20° C

    Science.gov (United States)

    Broadhurst, C. Leigh; Schmidt, Walter F.; Kim, Moon S.; Nguyen, Julie K.; Qin, Jianwei; Chao, Kuanglin; Bauchan, Gary L.; Shelton, Daniel R.

    2016-05-01

    The structural, cognitive and visual development of the human brain and retina strictly require long-chain polyunsaturated fatty acids (LC-PUFA). Excluding water, the mammalian brain is about 60% lipid. One of the great unanswered questions with respect to biological science in general is the absolute necessity of the LC-PUFA docosahexaenoic acid (DHA; 22:6n-3) in these fast signal processing tissues. A lipid of the same chain length with just one less diene group, docosapentaenoic acid (DPA; 22:5n-6) is fairly abundant in terrestrial food chains yet cannot substitute for DHA. Gradient Temperature Raman spectroscopy (GTRS) applies the temperature gradients utilized in differential scanning calorimetry to Raman spectroscopy, providing a straightforward technique to identify molecular rearrangements that occur near and at phase transitions. Herein we apply GTRS to DPA, and DHA from -100 to 20°C. 20 Mb three-dimensional data arrays with 1°C increments and first/second derivatives allows complete assignment of solid, liquid and transition state vibrational modes, including low intensity/frequency vibrations that cannot be readily analyzed with conventional Raman. DPA and DHA show significant spectral changes with premelting (-33 and -60°C, respectively) and melting (-27 and -44°C, respectively). The CH2-(HC=CH)-CH2 moieties are not identical in the second half of the DHA and DPA structures. The DHA molecule contains major CH2 twisting (1265 cm-1) with no noticeable CH2 bending, consistent with a flat helical structure with small pitch. Further modeling of neuronal membrane phospholipids must take into account this structure for DHA, which would be configured parallel to the hydrophilic head group line.

  2. Profiles of bile acids and their glucuronide and sulphate conjugates in the serum, urine and bile from patients undergoing bile drainage.

    OpenAIRE

    Takikawa, H; Beppu, T; Seyama, Y

    1985-01-01

    Bile acid profiles in serum, urine, and bile from patients undergoing bile drainage and the changes of serum bile acids after bile drainage were studied. Bile acids were separated into non-glucuronidate-non-sulphate, glucuronidated, and sulphated fractions and were measured by mass fragmentography using conjugates of deuterium labelled bile acids as internal standards. Glucuronidated and sulphated bile acids contribute 14-32% and 16-44% of serum bile acids, 4-11% and 61-82% of urine bile acid...

  3. Mutagenicity and cytotoxicity of two regioisomeric mercapturic acids and cysteine S-conjugates of trichloroethylene.

    NARCIS (Netherlands)

    Commandeur, J.N.M.; Boogaard, P.J.; Mulder, G.J.; Vermeulen, N.P.E.

    1991-01-01

    The mutagenicity, cytotoxicity and metabolism of two regioisomic l-cysteine- and N-acetyl-l-cysteine-S-conjugates of trichloroethylene were studied. The 1,2-dichlorovinyl(1,2-DCV) isomers of both the cysteine conjugate and the mercapturate were much stronger mutagens in the Ames test with Salmonella

  4. Conjugated linoleic acid ameliorates inflammation-induced colorectal cancer in mice through activation of PPARgamma.

    Science.gov (United States)

    Evans, Nicholas P; Misyak, Sarah A; Schmelz, Eva M; Guri, Amir J; Hontecillas, Raquel; Bassaganya-Riera, Josep

    2010-03-01

    Conjugated linoleic acid (CLA) exerts a protective effect on experimental inflammatory bowel disease and shows promise as a chemopreventive agent against colorectal cancer (CRC) in mice, although the mechanisms by which it exerts its beneficial effects against malignancies in the gut are not completely understood. Mice lacking PPARgamma in immune and epithelial cells and PPARgamma-expressing littermates were fed either control or CLA-supplemented (1 g CLA/100 g) diets to determine the role of PPARgamma in inflammation-induced CRC. To induce tumor formation and colitis, mice were treated with azoxymethane and then challenged with 2% dextran sodium sulfate, respectively. Dietary CLA ameliorated disease activity, decreased colitis, and prevented adenocarcinoma formation in the PPARgamma-expressing floxed mice but not in the tissue-specific PPARgamma-null mice. Dietary CLA supplementation significantly decreased the percentages of macrophages in the mesenteric lymph nodes (MLN) regardless of the genotype and increased regulatory T cell numbers in MLN of PPARgamma-expressing, but not in the tissue-specific, PPARgamma-null mice. Colonic tumor necrosis factor-alpha mRNA expression was significantly suppressed in CLA-fed, PPARgamma-expressing mice. This study suggests CLA ameliorates colitis and prevents tumor formation in part through a PPARgamma-dependent mechanism.

  5. The effect of conjugated linoleic acid supplementation on the nutritional status of COPD patients.

    Science.gov (United States)

    Ghobadi, Hassan; Matin, Somaieh; Nemati, Ali; Naghizadeh-Baghi, Abbas

    2016-01-01

    COPD patients are susceptible to anorexia, reduction of caloric intake, weight loss, and malnutrition. One of the possible mechanisms is the increase of inflammatory markers such as interleukin 1β (IL 1β ), is highly correlated with anorexia. Considering the anti-inflammatory role of conjugated linoleic acid (CLA), this study aimed to investigate the effect of CLA supplementation on the nutritional status of COPD patients. In a double-blind clinical trial, 93 COPD patients who volunteered to participate in the study and who filled out a written consent form, were randomly assigned to control or supplementation groups. The patients in the supplementation group received 3.2 g of CLA on a daily basis for 6 weeks, while those in the control group received placebo on a daily basis for 6 weeks. For IL 1β assessment, the patients' anthropometric indices and appetite score were checked and their blood samples were collected both before and after the treatment. Moreover, in order to investigate the changes in the caloric intake trend during the study, their dietary intake levels were assessed using 24-hour dietary recall, 3 days a week at the onset, in the 4th week, and at the end of the study. Eventually, 90 patients completed the study. The results demonstrated a significant increase in appetite score ( P =0.001), average caloric intake ( P =0.01), and macronutrient intake ( P nutritional status of patients suffering from COPD through adjusting the serum level of IL 1β .

  6. Surface-modified silk hydrogel containing hydroxyapatite nanoparticle with hyaluronic acid-dopamine conjugate.

    Science.gov (United States)

    Kim, Hyung Hwan; Park, Jong Bo; Kang, Min Ji; Park, Young Hwan

    2014-09-01

    Silk fibroin/hydroxyapatite (SF/HAp) composite hydrogels were fabricated in this study, having different HAp contents (0-33 wt%) in SF matrix hydrogel. Surface modification of HAp nanoparticle with hyaluronic acid (HA)-dopamine (DA) conjugate improved a dispersibility of HAp in aqueous SF solution due to its negatively charged surface and therefore, fabrication of the SF composite hydrogel having HAp nanoparticles inside could be possible. Zeta potential of surface-modified HAP was examined by ELS. It demonstrates that surface of HAp was well modified to a negative charge with HA-DA. Morphological structure of SF hydrogel containing surface-modified HAp was examined by FE-SEM for analyzing pore structure of hydrogel and deposition of HAp nanoparticle in SF hydrogel. It was found that HAp nanoparticles were uniformly deposited on the pore wall of SF hydrogel. Structural characteristics of SF/HAp composite hydrogel was performed using X-ray diffraction and FT-IR analysis. It was found that β-sheet crystal conformation of SF was significantly influenced by the HAp content during gelation of a mixture of SF and HAp. As a result of MTT assay, the SF/HAp composite hydrogel showed excellent cell proliferation ability. Therefore, it is expected that SF hydrogel containing HAp nanoparticles has a high potential as bone regeneration scaffold. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Synthesis of diethylenetriaminepentaacetic acid conjugated inulin and utility for cellular uptake of liposomes

    International Nuclear Information System (INIS)

    Essien, H.; Lai, J.Y.; Hwang, K.J.

    1988-01-01

    The synthesis, binding of radioactive cations, liposomal encapsulation, and biodistribution of the oxidized-inulin reaction product with ethylenediamine and diethylenetriaminepentaacetic acid (4) are described. The four-step synthesis of the inulin derivative proceeded in a good overall yield of 72%. The complex of the inulin derivative with either 67 Ga3+ or 111 In3+ was stable in vivo and did not readily distribute into tissues, being excreted primarily in urine after intravenous administration to mice. The liposome-entrapped inulin derivative can be loaded with radioactive heavy metal cations by mobile ionophores in high radiochemical yields of 80-91%. Following the intravenous administration of the liposomal encapsulation of the indium-111-labeled inulin derivative, the entrapped compound had a biodistribution characteristic of liposomes and allowed an estimation of the extent of the intracellular uptake of liposomes. The ability of the inulin derivative to chelate many different types of metals will allow the use of this probe for studying subtle differences in tissue distribution resulting from different drug targeting or delivery protocols in the same animal by multiple labeling techniques. Moreover, the chelate-conjugated inulin permits studies of the applications of drug delivery systems in primates or human subjects by noninvasive techniques such as gamma-scintigraphic or nuclear magnetic resonance imaging methods

  8. Mathematical Modelling to Predict Oxidative Behaviour of Conjugated Linoleic Acid in the Food Processing Industry

    Directory of Open Access Journals (Sweden)

    Aitziber Ojanguren

    2013-06-01

    Full Text Available Industrial processes that apply high temperatures in the presence of oxygen may compromise the stability of conjugated linoleic acid (CLA bioactive isomers. Statistical techniques are used in this study to model and predict, on a laboratory scale, the oxidative behaviour of oil with high CLA content, controlling the limiting factors of food processing. This modelling aims to estimate the impact of an industrial frying process (140 °C, 7 L/h air on the oxidation of CLA oil for use as frying oil instead of sunflower oil. A factorial design was constructed within a temperature (80–200 °C and air flow (7–20 L/h range. Oil stability index (Rancimat method was used as a measure of oxidation. Three-level full factorial design was used to obtain a quadratic model for CLA oil, enabling the oxidative behaviour to be predicted under predetermined process conditions (temperature and air flow. It is deduced that temperatures applied in food processes affect the oxidation of CLA to a greater extent than air flow. As a result, it is estimated that the oxidative stability of CLA oil is less resistant to industrial frying than sunflower oil. In conclusion, thanks to the mathematical model, a good choice of the appropriate industrial food process can be selected to avoid the oxidation of the bioactive isomers of CLA, ensuring its functionality in novel applications.

  9. The effects of conjugated linoleic acids on breast cancer: A systematic review

    Directory of Open Access Journals (Sweden)

    Arman Arab

    2016-01-01

    Full Text Available Recently prevention strategies for breast cancer are focused on lifestyle modification such as diet. Some dietary factors such as Conjugated linoleic acid (CLA can lower the risk of breast cancer, metastasis and some factors concerning this malignancy. Many studies have been established in this field, but their results are inconsistent. Therefore, we evaluated this association based on systematic review among published scientific literature. We performed an electronic search using PubMed, Cochrane, Scopus, Google Scholar and Persian database (Iran Medex, magiran to identify relevant studies. We summarized the findings of 8 papers in this review. Although, three cohort studies were not overall identified a protective effect of CLA dietary intake or CLA content in breast tissue on breast cancer incidence, metastasis and death, one of them showed an inverse association after adjusting for age. Also, among case-control studies a weak inverse association between breast cancer risk and CLA dietary intake and serum levels among post-menopausal women was reported. Besides, a clinical trial showed that some indicator of breast tumor decreased after CLA administration among women with breast adenocarcinoma. Lacking published evidence suggested inconsistent results. So, further well-designed studies are required, particularly in considering the main breast cancer risk factors.

  10. Concentrations of retinol and tocopherols in the milk of cows supplemented with conjugated linoleic acid.

    Science.gov (United States)

    Gessner, D K; Most, E; Schlegel, G; Kupczyk, K; Schwarz, F J; Eder, K

    2015-12-01

    This study was performed to investigate the hypothesis that supplementation of conjugated linoleic acid (CLA) changes the concentrations of retinol and tocopherols in the milk of cows. To investigate this hypothesis, H