Sample records for arachidonic acid

  1. The Property and Application of Arachidonic Acid

    Institute of Scientific and Technical Information of China (English)

    王相勤; 姚建铭; 袁成凌; 王纪; 余增亮


    Arachidonic acid (AA) is one of the most important PUFAs (polyunsaturated fatty acids) in human body. A high-yield arachidonic acid-producing strain (mortierella alpina) was selected by ion implantation (the relative content of arachidonic acid is 70.2% among all fatty acids). This paper mainly introduced the structure, distribution, source, physiologic healthcare function and application of AA.

  2. Dietary arachidonic acid in perinatal nutrition

    DEFF Research Database (Denmark)

    Lauritzen, Lotte; Fewtrell, Mary; Agostoni, Carlo


    Arachidonic acid (AA) is supplied together with docosahexaenoic acid (DHA) in infant formulas, but we have limited knowledge about the effects of supplementation with either of these long-chain polyunsaturated fatty acids (LCPUFA) on growth and developmental outcomes. AA is present in similar lev...

  3. [Studies on arachidonic acid production by Mortierella]. (United States)

    Bao, S; Zhu, F; Lin, W; Yao, R


    The effects of the incubation temperature, initial pH of the medium, carbon source and nitrogen source on the production of arachidonic acid by Mortierella sp. M10 were studied. Thought orthogonal experiments, the optimum culture medium was obtained (g/L): glucose, 100; yeast extract, 10; KNO3, 4.0; KH2PO4, 2.0; CaCl2.2H2O, 0.1; MgSO4.7H2O, 0.5; FeCl3.6H2O, 0.015; ZnSO4.7H2O, 0.0075; CuSO4.5H2O, 0.0005. Under the optimum culture conditions, the dry cell weight and arachidonic acid was 33.51 g/L and 0.827 g/L, respectively. The flask culture process was analysed.

  4. Arachidonic acid metabolites in pathogenic yeasts

    Directory of Open Access Journals (Sweden)

    Ells Ruan


    Full Text Available Abstract Although most of what is known about the biology and function of arachidonic acid metabolites comes from the study of mammalian biology, these compounds can also be produced by lower eukaryotes, including yeasts and other fungi. It is also in this group of organisms that the least is known about the metabolic pathways leading to the production of these compounds as well as the functions of these compounds in the biology of fungi and yeasts. This review will deal with the discovery of oxylipins from polyunsaturated fatty acids, and more specifically the arachidonic acid derived eicosanoids, such as 3-hydroxy eicosatetraenoic acid, prostaglandin F2α and prostaglandin E2, in yeasts starting in the early 1990s. This review will also focus on what is known about the metabolic pathways and/or proteins involved in the production of these compounds in pathogenic yeasts. The possible roles of these compounds in the biology, including the pathology, of these organisms will be discussed.

  5. Extracellular and intracellular arachidonic acid-induced contractions in rat aorta

    NARCIS (Netherlands)

    Filipeanu, CM; Brailoiu, E; Petrescu, G; Nelemans, SA


    Arachidonic acid induced contractions of de-endothelized rat aortic rings. A more potent effect was obtained after intracellular administration of arachidonic acid using liposomes. Contractions induced by extracellular arachidonic acid were inhibited similarly to phenylephrine-induced contractions b

  6. Metabolic flux analysis on arachidonic acid fermentation

    Institute of Scientific and Technical Information of China (English)

    JIN Mingjie; HUANG He; ZHANG Kun; YAN Jie; GAO Zhen


    The analysis of flux distributions in metabolic networks has become an important approach for understanding the fermentation characteristics of the process.A model of metabolic flux analysis of arachidonic acid (AA) synthesis in Mortierella alpina ME-1 was established and carbon flux distributions were estimated in different fermentation phases with different concentrations of N-source.During the exponential,decelerating and stationary phase,carbon fluxes to AA were 3.28%,8.80% and 6.97%,respectively,with sufficient N-source broth based on the flux of glucose uptake,and those were increased to 3.95%,19.21% and 39.29%,respectively,by regulating the shifts of carbon fluxes via fermentation with limited N-source broth and adding 0.05%NaNO3 at 96 h.Eventually AA yield was increased from 1.3 to 3.5 g.L-1.These results suggest a way to improve AA fermentation,that is,fermentation with limited N-source broth and adding low concentration N-source during the stationary phase.

  7. Mechanism of arachidonic acid action on syntaxin-Munc18. (United States)

    Connell, Emma; Darios, Frédéric; Broersen, Kerensa; Gatsby, Naomi; Peak-Chew, Sew-Yeu; Rickman, Colin; Davletov, Bazbek


    Syntaxin and Munc18 are, in tandem, essential for exocytosis in all eukaryotes. Recently, it was shown that Munc18 inhibition of neuronal syntaxin 1 can be overcome by arachidonic acid, indicating that this common second messenger acts to disrupt the syntaxin-Munc18 interaction. Here, we show that arachidonic acid can stimulate syntaxin 1 alone, indicating that it is syntaxin 1 that undergoes a structural change in the syntaxin 1-Munc18 complex. Arachidonic acid is incapable of dissociating Munc18 from syntaxin 1 and, crucially, Munc18 remains associated with syntaxin 1 after arachidonic-acid-induced syntaxin 1 binding to synaptosomal-associated protein 25 kDa (SNAP25). We also show that the same principle operates in the case of the ubiquitous syntaxin 3 isoform, highlighting the conserved nature of the mechanism of arachidonic acid action. Neuronal soluble N-ethyl maleimide sensitive factor attachment protein receptors (SNAREs) can be isolated from brain membranes in a complex with endogenous Munc18, consistent with a proposed function of Munc18 in vesicle docking and fusion.

  8. Human monocyte differentiation stage affects response to arachidonic acid. (United States)

    Escobar-Alvarez, Elizabeth; Pelaez, Carlos A; García, Luis F; Rojas, Mauricio


    AA-induced cell death mechanisms acting on human monocytes and monocyte-derived macrophages (MDM), U937 promonocytes and PMA-differentiated U937 cells were studied. Arachidonic acid induced apoptosis and necrosis in monocytes and U937 cells but only apoptosis in MDM and U937D cells. AA increased both types of death in Mycobacterium tuberculosis-infected cells and increased the percentage of TNFalpha+ cells and reduced IL-10+ cells. Experiments blocking these cytokines indicated that AA-mediated death was TNFalpha- and IL-10-independent. The differences in AA-mediated cell death could be explained by high ROS, calpain and sPLA-2 production and activity in monocytes. Blocking sPLA-2 in monocytes and treatment with antioxidants favored M. tuberculosis control whereas AA enhanced M. tuberculosis growth in MDM. Such evidence suggested that AA-modulated effector mechanisms depend on mononuclear phagocytes' differentiation stage.

  9. DMPD: Regulation of arachidonic acid release and cytosolic phospholipase A2activation. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 10080535 Regulation of arachidonic acid release and cytosolic phospholipase A2activation...on of arachidonic acid release and cytosolic phospholipase A2activation. PubmedID 10080535 Title Regulation ...of arachidonic acid release and cytosolic phospholipase A2activation. Authors Gij

  10. 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

  11. 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.

  12. The Essentiality of Arachidonic Acid in Infant Development

    Directory of Open Access Journals (Sweden)

    Kevin B. Hadley


    Full Text Available Arachidonic acid (ARA, 20:4n-6 is an n-6 polyunsaturated 20-carbon fatty acid formed by the biosynthesis from linoleic acid (LA, 18:2n-6. This review considers the essential role that ARA plays in infant development. ARA is always present in human milk at a relatively fixed level and is accumulated in tissues throughout the body where it serves several important functions. Without the provision of preformed ARA in human milk or infant formula the growing infant cannot maintain ARA levels from synthetic pathways alone that are sufficient to meet metabolic demand. During late infancy and early childhood the amount of dietary ARA provided by solid foods is low. ARA serves as a precursor to leukotrienes, prostaglandins, and thromboxanes, collectively known as eicosanoids which are important for immunity and immune response. There is strong evidence based on animal and human studies that ARA is critical for infant growth, brain development, and health. These studies also demonstrate the importance of balancing the amounts of ARA and DHA as too much DHA may suppress the benefits provided by ARA. Both ARA and DHA have been added to infant formulas and follow-on formulas for more than two decades. The amounts and ratios of ARA and DHA needed in infant formula are discussed based on an in depth review of the available scientific evidence.

  13. Dietary arachidonic acid in perinatal nutrition: a commentary. (United States)

    Lauritzen, Lotte; Fewtrell, Mary; Agostoni, Carlo


    Arachidonic acid (AA) is supplied together with docosahexaenoic acid (DHA) in infant formulas, but we have limited knowledge about the effects of supplementation with either of these long-chain polyunsaturated fatty acids (LCPUFA) on growth and developmental outcomes. AA is present in similar levels in breast milk throughout the world, whereas the level of DHA is highly diet dependent. Autopsy studies show similar diet-dependent variation in brain DHA, whereas AA is little affected by intake. Early intake of DHA has been shown to affect visual development, but the effect of LCPUFA on neurodevelopment remains to be established. Few studies have found any functional difference between infants supplemented with DHA alone compared to DHA+AA, but some studies show neurodevelopmental advantages in breast-fed infants of mothers supplemented with n-3 LCPUFA alone. It also remains to be established whether the AA/DHA balance could affect allergic and inflammatory outcomes later in life. Disentangling effects of genetic variability and dietary intake on AA and DHA-status and on functional outcomes may be an important step in the process of determining whether AA-intake is of any physiological or clinical importance. However, based on the current evidence we hypothesize that dietary AA plays a minor role on growth and development relative to the impact of dietary DHA.

  14. Arachidonic acid is a chemoattractant for Dictyostelium discoideum cells

    Indian Academy of Sciences (India)

    Ralph H Schaloske; Dagmar Blaesius; Christina Schlatterer; Daniel F Lusche


    Cyclic AMP (cAMP) is a natural chemoattractant of the social amoeba Dictyostelium discoideum. It is detected by cell surface cAMP receptors. Besides a signalling cascade involving phosphatidylinositol 3,4,5-trisphosphate (PIP3), Ca2+ signalling has been shown to have a major role in chemotaxis. Previously, we have shown that arachidonic acid (AA) induces an increase in the cytosolic Ca2+ concentration by causing the release of Ca2+ from intracellular stores and activating influx of extracellular Ca2+. Here we report that AA is a chemoattractant for D. discoideum cells differentiated for 8–9 h. Motility towards a glass capillary filled with an AA solution was dose-dependent and qualitatively comparable to cAMP-induced chemotaxis. Ca2+ played an important role in AA chemotaxis of wild-type Ax2 as ethyleneglycolbis(b-aminoethyl)-N,N,N′,N′-tetraacetic acid (EGTA) added to the extracellular buffer strongly inhibited motility. In the HM1049 mutant whose iplA gene encoding a putative Ins(1,4,5)P3-receptor had been knocked out, chemotaxis was only slightly affected by EGTA. Chemotaxis in the presence of extracellular Ca2+ was similar in both strains. Unlike cAMP, addition of AA to a cell suspension did not change cAMP or cGMP levels. A model for AA chemotaxis based on the findings in this and previous work is presented.

  15. Arachidonic acid production by Mortierella alpina using raw crop materials

    Directory of Open Access Journals (Sweden)

    Ganggang Cao


    Full Text Available Background. Arachidonic acid (ARA is one of the three essential fatty acids, and it is important for human body to keep healthy and is widely used. At present, expensive materials such as glucose and yeast extract are generally reported to be optimal for ARA production. A new cost-effective fermentation process including cheaper material for ARA production is of great signifi cance. Material and methods. Feasibility of using corn meal and powdered soybean for fungal growth and lipid accumulation was evaluated by means of single factor test. N-hexadecane concentration was optimized, and the effect of temperature on biomass and ARA content was examined. Results. Mortierella alpina made better use of the aforementioned material as carbon and nitrogen sources for both hyphae growth and ARA production compared with glucose and yeast extract. Maximal levels of 10.9 g/L ARA and 26.1 g/L total lipids were obtained when 66 g/L corn meal, 54 g/L soybean meal and 6% (v/v n-hexadecane were supplemented. A temperature-shift strategy involved three steps, namely, 30°C (3 days – 25°C (4 days – 20°C (4 days, which further improved ARA production by 24.7%. Conclusion. Several factors such as carbon and nitrogen sources, temperature and dissolved oxygen had great infl uence on biomass and microbial oil production. Mortierella alpina preferred corn and soybean meal compared with glucose and yeast extract, which would surely alleviate the high cost of ARA production. Based on this study, the new process is both low cost and practicable.

  16. Correlation between arachidonic acid oxygenation and luminol-induced chemiluminescence in neutrophils: inhibition by diethyldithiocarbamate. (United States)

    Chabannes, B; Perraut, C; El Habib, R; Moliere, P; Pacheco, Y; Lagarde, M


    Neutrophils from allergic subjects were hypersensitive to stimulation by low calcium ionophore concentration (0.15 microM), resulting in an increased formation of leukotriene B4 (LTB4), 5S-hydroxy-6,8,11,14-(E,Z,Z,Z)-eicosatetraenoic acid (5-HETE), and other arachidonic acid metabolites through the 5-lipoxygenase pathway. In parallel, luminol-dependent chemiluminescence was also higher in neutrophils from allergic patients at the basal state and after stimulation by calcium ionophore, revealing an enhancement of radical oxygen species and peroxide production. The activity of glutathione peroxidase, the main enzyme responsible for hydroperoxide reduction, was lowered in these cells. Diethyl-dithiocarbamate (DTC) induced a concentration-dependent decrease in chemiluminescence and arachidonic acid metabolism after neutrophil stimulation. These data show that the elevation of arachidonic acid metabolism in neutrophils from allergic patients is strongly correlated with oxidative status. This elevation may be the consequence of an increased cellular hydroperoxide known to activate 5-lipoxygenase (5-LOX) activity and/or an increased arachidonic acid availability, due either to phospholipase A2 (PLA2) activation or inhibition of arachidonate reesterification into phospholipids. Lowering this oxidative status was associated with a concomitant decrease of this metabolism. Our results suggest that the effect of DTC may be the consequence of an inhibition of peroxyl radical and cellular lipid hydroperoxide production. Thus, DTC may modulate arachidonic acid metabolism in neutrophils by modulating the cellular hydroperoxide level.

  17. 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 e

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

    NARCIS (Netherlands)

    Hadders-Algra, Mijna


    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

  19. Lower fetal status of docosahexaenoic acid, arachidonic acid and essential fatty acids is associated with less favorable neonatal neurological condition

    NARCIS (Netherlands)

    Dijck-Brouwer, DAJ; Hadders-Algra, M; Bouwstra, H; Decsi, T; Boehm, G; Martini, IA; Boersma, ER; Muskiet, FAJ


    Long-chain polyunsaturated fatty acids, notably arachidonic (AA) and docosahexaenoic (DHA) acids are abundant in brain and may be conditionally essential in fetal life. We investigated umbilical artery (UA) and vein (UV) fatty acid compositions and early neonatal neurological condition in 317 term i

  20. 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.


    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, double-blin

  1. Arachidonic acid reduces the stress response of gilthead seabream Sparus aurata L.

    NARCIS (Netherlands)

    Anholt, R.D. van; Spanings, F.A.T.; Koven, W.M.; Nixon, O.; Wendelaar Bonga, S.E.


    In this study the influence of the dietary level of the fatty acid arachidonic acid (ArA, 20:4n-6) was determined on the acute stress response and osmoregulation of adult gilthead seabream Sparus aurata L. Seabream were fed a diet containing either 0.9% or 2.4% of total fatty acids as ArA for 18 day

  2. Research on Arachidonic Acid and Eicosapentaenoic Acid Anabolic Metabolism in Diasporangium sp.

    Institute of Scientific and Technical Information of China (English)

    DAI Chuan-chao; XU Yu-fen; XIA Shun-xiang; ZHAO Mo; YE Yu-cheng


    The fatty acids of a strain of Diasporangium sp.had been analyzed by using GC-MS.The fatty acids of twenty mutants were determined.Based on these results,the producing of eicosapentaenoic acid(EPA)supposed via 18∶2,18∶3,20∶3,20∶4 which all belong to ω-6 fatty acids.The ω-3 desaturation was undertaken at arachidonic acid(AA).In addition,mutant strains resulted in enhanced content of AA which could get two times more than initial strain,but no compact on EPA.

  3. The Arachidonic Acid Metabolome Serves as a Conserved Regulator of Cholesterol Metabolism

    NARCIS (Netherlands)

    Demetz, Egon; Schroll, Andrea; Auer, Kristina; Heim, Christiane; Patsch, Josef R.; Eller, Philipp; Theurl, Markus; Theurl, Igor; Theurl, Milan; Seifert, Markus; Lener, Daniela; Stanzl, Ursula; Haschka, David; Asshoff, Malte; Dichtl, Stefanie; Nairz, Manfred; Huber, Eva; Stadlinger, Martin; Moschen, Alexander R.; Li, Xiaorong; Pallweber, Petra; Scharnagl, Hubert; Stojakovic, Tatjana; Maerz, Winfried; Kleber, Marcus E.; Garlaschelli, Katia; Uboldi, Patrizia; Catapano, Alberico L.; Stellaard, Frans; Rudling, Mats; Kuba, Keiji; Imai, Yumiko; Arita, Makoto; Schuetz, John D.; Pramstaller, Peter P.; Tietge, Uwe J. F.; Trauner, Michael; Norata, Giuseppe D.; Claudel, Thierry; Hicks, Andrew A.; Weiss, Guenter; Tancevski, Ivan


    Cholesterol metabolism is closely interrelated with cardiovascular disease in humans. Dietary supplementation with omega-6 polyunsaturated fatty acids including arachidonic acid (AA) was shown to favorably affect plasma LDL-C and HDL-C. However, the underlying mechanisms are poorly understood. By co

  4. Dietary supplementation with arachidonic acid in tilapia (Oreochromis mossambicus) reveals physiological effects not mediated by prostaglandins.

    NARCIS (Netherlands)

    Anholt, R.D. van; Spanings, F.A.T.; Koven, W.M.; Wendelaar Bonga, S.E.


    This study aims to clarify the role of the polyunsaturated fatty acid arachidonic acid (ArA, 20:4n-6) in the stress response of Mozambique tilapia (Oreochromis mossambicus). ArA is converted into eicosanoids, including prostaglandins, which can influence the response to stressors. Tilapia, a species

  5. Production of metabolic products of arachidonic acid during cell-cell interactions

    Energy Technology Data Exchange (ETDEWEB)

    Marcus, A.J.; Safier, L.B.; Broekman, M.J.; Ullman, H.L.; Islam, N.; Sorrell, T.C.; Serhan, C.N.; Weissmann, G.; Oglesby, T.D.; Gorman, R.R.


    Interactions of human platelets and neutrophils were studied with particular reference to the arachidonic acid pathway. Suspensions of (3H)arachidonate-labeled platelets and unlabeled neutrophils were stimulated with ionophore A23187. We detected several radioactive arachidonate metabolites, which are not produced by platelets alone. These included (3H)-labeled leukotriene B4 (LTB4), dihydroxy-eicosatetraeonic acid (DiHETE), and 5-hydroxy-eicosatetraenoic acid (5-HETE). DiHETE was formed when the platelet product (3H)12-HETE was added to ionophore-stimulated neutrophils. In addition, DiHETE was the major metabolite when (3H)5-HETE, a neutrophil arachidonate product, was added to stimulated platelets. We therefore suggest that upon stimulation, platelet-derived arachidonate can serve as precursor for the neutrophil-derived eicosanoids LTB4 and 5-HETE, and the platelet-derived product 12-HETE can be metabolized to DiHETE by stimulated human neutrophils. More recently we have shown that 12-HETE from thrombin-stimulated platelets can also be metabolized to a new product, 12,20-DiHETE, by

  6. Effect of amiloride on arachidonic acid and histamine release from rat mast cells

    DEFF Research Database (Denmark)

    Linnebjerg, H.; Hansen, Harald S.; Jensen, B.


    The effect of a putative Na/H exchange inhibition on histamine and [C]arachidonic acid ([C]AA) release has been examined in rat peritoneal mast cells, using either addition of amiloride or removal of extracellular Na. The cells were stimulated by non-immunological agents, i.e. calcium ionophore A...

  7. Effect of gomisin A (TJN-101) on the arachidonic acid cascade in macrophages. (United States)

    Ohkura, Y; Mizoguchi, Y; Morisawa, S; Takeda, S; Aburada, M; Hosoya, E


    It has been reported that leukotrienes (LTs) may play a role in inflammatory liver diseases, and several inhibitors of LTs show an inhibitory effect on experimental liver injuries. In this study, the effect of Gomisin A (TJN-101), which is a lignan component of schisandra fruits, on the arachidonic acid cascade in macrophages was examined to explain the mechanisms of the inhibitory effect of TJN-101 on liver injuries. The production of leukotriene B4 was suppressed by treatment with TJN-101, while the activity of 5-lipoxygenase was not affected. The release of arachidonic acid from macrophages stimulated with fMet-Leu-Phe or the Ca++ ionophore A23187 was suppressed by treatment with TJN-101. The activity of phospholipase A2 was not affected by treatment with TJN-101. These results suggested that TJN-101 produces an inhibitory effect on the biosynthesis of LTs by preventing the release of arachidonic acid, and it was thought that the preventive effect on the arachidonic acid cascade may be partially associated with the inhibitory effect of TJN-101 on liver injuries.

  8. Uptake and release of arachidonic acid by platelets and cultured cells

    Energy Technology Data Exchange (ETDEWEB)

    Neufeld, E.J.


    The release by thrombin of arachidonic acid, and the accompanying phospholipid metabolism, were studied in human platelets. At 23/sup 0/C, arachidonate release was half-maximal by 10-30 sec after stimulation, and preceded substantial increase in phosphatidic acid (PA) mass. (/sup 3/H)-glycerol-labeled platelets synthesized phospholipids from (/sup 3/H) PA at a rate of 0.08-0.3 nmol/min/10/sup 9/ cells at 37/sup 0/C. This rate of PA turnover was not enhanced by thrombin stimulation. Thus, an increase in PA mass is not a necessary event in the pathway loading to arachidonate release, and the release of several nmol of arachidonate from PI in the first minute after thrombin stimulation could not have arisen via PA as an intermediate. Biological function of arachidonate-specific acyl-CoA synthetase was examined in platelets and in HSDM/sub 1/C/sub 1/ murine fibrosarcoma cells. Washed platelets were found to take up and esterify into cellular phospholipids eicosanoid precursor fatty acids present at concentrations of 5-500 nM. The uptake process was saturable with respect to fatty acid concentration, with apparent K/sub m/ less than or equal to 85 nM. Stearate, oleate and linoleate were taken up less rapidly, and with higher apparent K/sub m/'s (greater than or equal to 170 nM). High affinity uptake was also found in HSDM/sub 1/C/sub 1/ cells. The fatty acid structural requirements of arachidonoyl-CoA synthetase were examined. Among common mammalian fatty acids, only eicosanoid precursors and docosahexaenoate could serve as substrates. These studies strongly suggest that the synthetase is required for normal eicosanoid homeostasis.

  9. Phosphate limitation promotes unsaturated fatty acids and arachidonic acid biosynthesis by microalgae Porphyridium purpureum. (United States)

    Su, Gaomin; Jiao, Kailin; Li, Zheng; Guo, Xiaoyi; Chang, Jingyu; Ndikubwimana, Theoneste; Sun, Yong; Zeng, Xianhai; Lu, Yinghua; Lin, Lu


    Polyunsaturated fatty acids (PUFAs) are highly appreciated on their nutritive value for human health and aquaculture. P. purpureum, one of the red microalgae acknowledged as a promising accumulator of ARA, was chosen as the target algae in the present research. Effects of sodium bicarbonate (0.04-1.2 g/L), temperature (25, 30 and 33 °C) and phosphate (0.00-0.14 g/L) on biomass yield, total fatty acids (TFA) and arachidonic acid (ARA) accumulation were investigated systemically. NaHCO3 dose of 0.8 g/L and moderate temperature of 30 °C were preferred. In addition, TFA and ARA production were significantly enhanced by an appropriate concentration of phosphate, and the highest TFA yield of 666.38 mg/L and ARA yield of 159.74 mg/L were obtained at a phosphate concentration of 0.035 g/L. Interestingly, with phosphate concentration continuing to fall, UFA/TFA and ARA/EPA ratios were increased accordingly, suggesting that phosphate limitation promoted unsaturated fatty acids and arachidonic acid biosynthesis. Low concentration of phosphate may be favored to increase the enzymatic activities of ∆6-desaturase, which played a key role in catalyzing the conversion of C16:0 to C18:2, and thus the selectivity of UFA increased. Meanwhile, the increase of ARA selectivity could be attributed to ω6 pathway promotion and ∆17-desaturase activity inhibition with phosphate limitation. Phosphate limitation strategy enhanced unsaturated fatty acids and ARA biosynthesis in P. purpureum, and can be applied in commercial scale manufacturing and commercialization of ARA.

  10. Incorporation and distribution of dihomo-gamma-linolenic acid, arachidonic acid, and eicosapentaenoic acid in cultured human keratinocytes

    Energy Technology Data Exchange (ETDEWEB)

    Punnonen, K.; Puustinen, T.; Jansen, C.T.


    Human keratinocytes in culture were labelled with /sup 14/C-dihomo-gamma-linolenic acid, /sup 14/C-arachidonic acid or /sup 14/C-eicosapentaenoic acid. All three eicosanoid precursor fatty acids were effectively incorporated into the cells. In phospholipids most of the radioactivity was recovered, in neutral lipids a substantial amount, and as free unesterified fatty acids only a minor amount. Most of the radioactivity was found in phosphatidylethanolamine which was also the major phospholipid as measured by phosphorous assay. The incorporation of dihomo-gamma-linolenic acid and arachidonic acid into lipid subfractions was essentially similar. Eicosapentaenoic acid was, however, much less effectively incorporated into phosphatidylinositol + phosphatidylserine and, correspondingly, more effectively into triacylglycerols as compared to the two other precursor fatty acids. Once incorporated, the distribution of all three precursor fatty acids was relatively stable, and only minor amounts of fatty acids were released into the culture medium during short term culture (two days). Our study demonstrates that eicosanoid precursor fatty acids are avidly taken up by human keratinocytes and esterified into membrane lipids. The clinical implication of this finding is that dietary manipulations might be employed to cause changes in the fatty acid composition of keratinocytes.

  11. Differential stimulation of luminol-enhanced chemiluminescence (CL) and arachidonic acid metabolism in rat peritoneal neutrophils

    Energy Technology Data Exchange (ETDEWEB)

    Sturm, R.J.; Adams, L.M.; Cullinan, C.A.; Berkenkopf, J.W.; Weichman, B.M.


    Phorbol 12-myristate, 13-acetate (PMA) induced the production of radical oxygen species (ROS) from rat peritoneal neutrophils as assessed by CL. ROS generation occurred in a time- (maximum at 13.5 min) and dose- (concentration range of 1.7-498 nM) related fashion. However, 166 nM PMA did not induce either cyclooxygenase (CO) or lipoxygenase (LPO) product formation by 20 min post-stimulation. Conversely, A23187, at concentrations between 0.1 and 10, stimulated both pathways of arachidonic acid metabolism, but had little or no effect upon ROS production. When suboptimal concentrations of PMA (5.5 nM) and A23187 (0.1-1 were coincubated with the neutrophils, a synergistic ROS response was elicited. However, arachidonic acid metabolism in the presence of PMA was unchanged relative to A12187 alone. Nordihydroguaiaretic acid (NDGA) inhibited both PMA-induced CL (IC/sub 50/ = 0.9 and A23187-induced arachidonic acid metabolism (IC/sub 50/ = 1.7 and 6.0 for LPO and CO, respectively). The mixed LPO-CO inhibitor, BW755C, behaved in a qualitatively similar manner to NDGA, whereas the CO inhibitors, indomethacin, piroxicam and naproxen had no inhibitory effect on ROS generation at concentrations as high as 100 These results suggest that NDGA and BW755C may inhibit CL and arachidonic acid metabolism by distinct mechanisms in rat neutrophils.

  12. The skeletal muscle arachidonic acid cascade in health and inflammatory disease. (United States)

    Korotkova, Marina; Lundberg, Ingrid E


    Muscle atrophy and weakness are often observed in patients with chronic inflammatory diseases, and are the major clinical features of the autoimmune myopathies, polymyositis and dermatomyositis. A general understanding of the pathogenesis of muscle atrophy and the impaired muscle function associated with chronic inflammatory diseases has not been clarified. In this context, arachidonic acid metabolites, such as the prostaglandin and leukotriene subfamilies, are of interest because they contribute to immune and nonimmune processes. Accumulating evidence suggests that prostaglandins and leukotrienes are involved in causing muscular pain and inflammation, and also in myogenesis and the repair of muscles. In this Review, we summarize novel findings that implicate prostaglandins and leukotrienes in the muscle atrophy and weakness that occur in inflammatory diseases of the muscles, with a focus on inflammatory myopathies. We discuss the role of the arachidonic acid cascade in skeletal muscle growth and function, and individual metabolites as potential therapeutic targets for the treatment of inflammatory muscle diseases.

  13. Expression analysis for genes involved in arachidonic acid biosynthesis in Mortierella alpina CBS 754.68

    Directory of Open Access Journals (Sweden)

    Hamid-Reza Samadlouie


    Full Text Available The time courses for production of fungal biomass, lipid, phenolic and arachidonic acid (ARA as well as expression of the genes involved in biosynthesis of ARA and lipid were examined in Mortierella alpina CBS 754.68. A significant increase in the arachidonic acid content in lipids that coincided with reduced levels of lipid was obtained. Reduced gene expression occurred presumably due to the steady reduction of carbon and nitrogen resources. However, these energy resources were inefficiently compensated by the breakdown of the accumulated lipids that in turn, induced up-regulated expression of the candidate genes. The results further indicated that the expression of the GLELO encoding gene is a rate-limiting step in the biosynthesis of ARA in the early growth phase.

  14. Immunohistochemical localization of key arachidonic acid metabolism enzymes during fracture healing in mice.

    Directory of Open Access Journals (Sweden)

    Hsuan-Ni Lin

    Full Text Available This study investigated the localization of critical enzymes involved in arachidonic acid metabolism during the initial and regenerative phases of mouse femur fracture healing. Previous studies found that loss of cyclooxygenase-2 activity impairs fracture healing while loss of 5-lipoxygenase activity accelerates healing. These diametric results show that arachidonic acid metabolism has an essential function during fracture healing. To better understand the function of arachidonic acid metabolism during fracture healing, expression of cyclooxygenase-1 (COX-1, cyclooxygenase -2 (COX-2, 5-lipoxygenase (5-LO, and leukotriene A4 hydrolase (LTA4H was localized by immunohistochemistry in time-staged fracture callus specimens. All four enzymes were detected in leukocytes present in the bone marrow and attending inflammatory response that accompanied the fracture. In the tissues surrounding the fracture site, the proportion of leukocytes expressing COX-1, COX-2, or LTA4H decreased while those expressing 5-LO remained high at 4 and 7 days after fracture. This may indicate an inflammation resolution function for 5-LO during fracture healing. Only COX-1 was consistently detected in fracture callus osteoblasts during the later stages of healing (day 14 after fracture. In contrast, callus chondrocytes expressed all four enzymes, though 5-LO appeared to be preferentially expressed in newly differentiated chondrocytes. Most interestingly, osteoclasts consistently and strongly expressed COX-2. In addition to bone surfaces and the growth plate, COX-2 expressing osteoclasts were localized at the chondro-osseous junction of the fracture callus. These observations suggest that arachidonic acid mediated signaling from callus chondrocytes or from callus osteoclasts at the chondro-osseous junction regulate fracture healing.

  15. Effects of fluticasone propionate inhalation on levels of arachidonic acid metabolites in patients with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Gert T. Verhoeven


    Full Text Available Background: In smoking COPD patients the bronchoalveolar lavage (BAL fluid contains high numbers of inflammatory cells. These cells might produce arachidonic acid (AA metabolites, which contribute to inflammation and an increased bronchomotor tone.

  16. Targeted Chiral Analysis of Bioactive Arachidonic Acid Metabolites Using Liquid-Chromatography-Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Clementina Mesaros


    Full Text Available A complex structurally diverse series of eicosanoids arises from the metabolism of arachidonic acid. The metabolic profile is further complicated by the enantioselectivity of eicosanoid formation and the variety of regioisomers that arise. In order to investigate the metabolism of arachidonic acid in vitro or in vivo, targeted methods are advantageous in order to distinguish between the complex isomeric mixtures that can arise by different metabolic pathways. Over the last several years this targeted approach has become more popular, although there are still relatively few examples where chiral targeted approaches have been employed to directly analyze complex enantiomeric mixtures. To efficiently conduct targeted eicosanoid analyses, LC separations are coupled with collision induced dissociation (CID and tandem mass spectrometry (MS/MS. Product ion profiles are often diagnostic for particular regioisomers. The highest sensitivity that can be achieved involves the use of selected reaction monitoring/mass spectrometry (SRM/MS; whereas the highest specificity is obtained with an SRM transitions between an intense parent ion, which contains the intact molecule (M and a structurally significant product ion. This review article provides an overview of arachidonic acid metabolism and targeted chiral methods that have been utilized for the analysis of the structurally diverse eicosanoids that arise.

  17. Evaluation of Bioequivalency and Toxicological Effects of Three Sources of Arachidonic Acid (ARA) in Domestic Piglets



    Arachidonic acid (ARA) and docosahexaenoic acid (DHA) are routinely added to infant formula to support growth and development. We evaluated the bioequivalence and safety of three ARA-rich oils for potential use in infant formula using the neonatal pig model. The primary outcome for bioequivalence was brain accretion of ARA and DHA. Days 3 to 22 of age, domestic pigs fed one of three formulas, each containing ARA at ~0.64% and DHA at ~0.34% total fatty acids (FA). Control diet ARA was provided...

  18. Arachidonic acid, an omega-6 fatty acid, induces cytoplasmic phospholipase A2 in prostate carcinoma cells. (United States)

    Hughes-Fulford, Millie; Tjandrawinata, Raymond R; Li, Chai-Fei; Sayyah, Sina


    For the past 60 years, dietary intake of essential fatty acids has increased. Moreover, the omega-6 fatty acids have recently been found to play an important role in regulation of gene expression. Proliferation of human prostate cells was significantly increased 48 h after arachidonic acid (AA) addition. We have analyzed initial uptake using nile red fluorescence and we found that the albumin conjugated AA is endocytosed into the cells followed by the induction of RNA within minutes, protein and PGE2 synthesis within hours. Here we describe that AA induces expression of cytosolic phospholipase A2 (cPLA2) in a dose-dependent manner and that this upregulation is dependent upon downstream synthesis of PGE2. The upregulation of cox-2 and cPLA2 was inhibited by flurbiprofen, a cyclooxygenase (COX) inhibitor, making this a second feed-forward enzyme in the eicosanoid pathway. Cox-2 specific inhibitors are known to inhibit colon and prostate cancer growth in humans; however, recent findings show that some of these have cardiovascular complications. Since cPLA2 is upstream in the eicosanoid pathway, it may be a good alternative for a pharmaceutical target for the treatment of cancer.

  19. Docosahexaenoic acid suppresses arachidonic acid-induced proliferation of LS-174T human colon carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Piet Habbel; Karsten H Weylandt; Katja Lichopoj; Johannes Nowak; Martin Purschke; Jing-Dong Wang; Cheng-Wei He; Daniel C Baumgart; Jing X Kang


    AIM: To investigate the impact of arachidonic acid (AA) and docosahexaenoic acid (DHA) and their combination on colon cancer cell growth.METHODS: The LS-174T colon cancer cell line was used to study the role of the prostaglandin precursor AA and the omega-3 polyunsaturated fatty acid DHA on cell growth. Cell viability was assessed in XTT assays. For analysis of cell cycle and cell death, flow cytometry and DAPI staining were applied. Expression of cyclooxygenase-2 (COX-2), p21 and bcl-2 in cells incubated with AA or DHA was examined by real-time RT-PCR. Prostaglandin E2 (PGE2) generation in the presence of AA and DHA was measured using a PGE2ELISA.RESULTS: AA increased cell growth, whereas DHA reduced viability of LS 174T cells in a time- and dosedependent manner. Furthermore, DHA down- regulated mRNA of bcl-2 and up-regulated p21. Interestingly,DHA was able to suppress AA-induced cell proliferation and significantly lowered AA-derived PGE2 formation.DHA also down-regulated COX-2 expression. In addition to the effect on PGE2 formation, DHA directly reduced PGE2-induced cell proliferation in a dosedependent manner.CONCLUSION: These results suggest that DHA can inhibit the pro-proliferative effect of abundant AA or PGE2.

  20. Eicosapentaenoic Acid, Arachidonic Acid and Eicosanoid Metabolism in Juvenile Barramundi Lates calcarifer. (United States)

    Salini, Michael J; Wade, Nicholas M; Araújo, Bruno C; Turchini, Giovanni M; Glencross, Brett D


    A two part experiment was conducted to assess the response of barramundi (Lates calcarifer; initial weight = 10.3 ± 0.03 g; mean ± S.D.) fed one of five diets with varying eicosapentaenoic acid (diets 1, 5, 10, 15 and 20 g/kg) or one of four diets with varying arachidonic acid (1, 6, 12, 18 g/kg) against a fish oil control diet. After 6 weeks of feeding, the addition of EPA or ARA did not impact on growth performance or feed utilisation. Analysis of the whole body fatty acids showed that these reflected those of the diets. The ARA retention demonstrated an inversely related curvilinear response to either EPA or ARA. The calculated marginal utilisation efficiencies of EPA and ARA were high (62.1 and 91.9 % respectively) and a dietary ARA requirement was defined (0.012 g/kg(0.796)/day). The partial cDNA sequences of genes regulating eicosanoid biosynthesis were identified in barramundi tissues, namely cyclooxygenase 1 (Lc COX1a, Lc COX1b), cyclooxygenase 2 (Lc COX2) and lipoxygenase (Lc ALOX-5). Both Lc COX2 and Lc ALOX-5 expression in the liver tissue were elevated in response to increasing dietary ARA, meanwhile expression levels of Lc COX2 and the mitochondrial fatty acid oxidation gene carnitine palmitoyltransferase 1 (Lc CPT1a) were elevated in the kidney. A low level of EPA increased the expression of Lc COX1b in the liver. Consideration should be given to the EPA to ARA balance for juvenile barramundi in light of nutritionally inducible nature of the cyclooxygenase and lipoxygenase enzymes.

  1. 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


    Institute of Scientific and Technical Information of China (English)


    Parietochloris incisa is an arachidonic acid-rich snow green alga. The main phy siological profiles, such as ash free dry weight (AFDW), chlorophyll, carotenoid , protein and total fatty acids (TFA), in this alga exposed to old culture super natant (OCS) at the decline phase or its crude ethyl acetate extracts (CEAE) wer e investigated by using tubular photobioreactors of different diameters. Results showed that both OCS and CEAE had strong inhibitory effect on the above physiol ogical parameters. The longer the culture was exposed to OCS and the more CEAE w ere added into the algal culture, the more the above physiological properties we re inhibited. Arachidonic acid (AA), the dominant component of fatty acids in th is alga, was also seriously inhibited with respect to total TFA, AFDW of cell ma ss, or culture volume, due to a probable reduction of enzymes activities catalyz ing chain elongation from C18:1ω9 to AA. These results incontestably evidenced t hat some CEAE dissolving substances existing in OCS, like auto-inhibitors, inhi bited P. incisa growth through feedback. Hence, any efficient removal of aut o-i nhibitors from algal culture to decrease their bioactivity could be good for max imal production of desired products like AA.


    Institute of Scientific and Technical Information of China (English)

    刘建国; 张成武; ZviCohen; AmosRichmond


    Parietochloris incisa is an arachidonic acid-rich snow green alga. The main physiological profiles, such as ash free dry weight (AFDW), chlorophyll, carotenoid, protein and total fatty acids (TFA), in this alga exposed to old culture supernatant (OCS) at the decline phase or its crude ethyl acetate extracts (CEAE) were investigated by using tubular photobioreactors of different diameters. Results showed that both OCS and CEAE had strong inhibitory effect on the above physiological parameters. The longer the culture was exposed to OCS and the more CEAE were added into the algal culture, the more the above physiological properties were inhibited. Arachidonic acid (AA), the dominant component of fatty acids in this alga, was also seriously inhibited with respect to total TFA, AFDW of cell mass, or culture volume, due to a prebable reduction of enzymes activities catalyzing chain elongation from C18:1ω9 to AA. These results incontestably evidenced that some CEAE dissolving substances existing in OCS, like auto-inhibitors, inhibited P. incisa growth through feedback. Hence, any efficient removal of auto-inhibitors from algal culture to decrease their bioactivity could be good for maximal production of desired products like AA.

  4. Physiological inhibitory effect of ocs in arachidonic acid-rich Parietochloris incisa (trebouxiophyceae, chlorophyta) (United States)

    Liu, Jian-Guo; Zhang, Cheng-Wu; Cohen, Zvi; Richmond, Amos


    Parietochloris incisa is an arachidonic acid-rich snow green alga. The main physiological profiles, such as ash free dry weight (AFDW), chlorophyll, carotenoid, protein and total fatty acids (TFA), in this alga exposed to old culture supernatant (OCS) at the decline phase or its crude ethyl acetate extracts (CEAE) were investigated by using tubular photobioreactors of different diameters. Results showed that both OCS and CEAE had strong inhibitory effect on the above physiological parameters. The longer the culture was exposed to OCS and the more CEAE were added into the algal culture, the more the above physiological properties were inhibited. Arachidonic acid (AA), the dominant component of fatty acids in this alga, was also seriously inhibited with respect to total TFA, AFDW of cell mass, or culture volume, due to a probable reduction of enzymes activities catalyzing chain elongation from C18; 1ω9 to AA. These results incontestably evidenced that some CEAE dissolving substances existing in OCS. like auto-inhibitors, inhibited P. incisa growth through feedback. Hence, any efficient removal of auto-inhibitors from algal culture to decrease their bioactivity could be good for maximal production of desired products like AA.

  5. 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


    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

  6. The effect of prostaglandin E2 and arachidonic acid on dentinogenesis in pigs. (United States)

    Burke, A; Weiler, H


    The rate of dentinogenesis for the pig is quantified and the effects of dietary arachidonic acid supplementation and/or exogenous prostaglandin on dentine formation are defined. Thirty-six pigs were randomised to four groups, receiving either standard or supplemented formula and either prostaglandin E2 or placebo injections for fifteen days. Double tetracycline banding is used to measure rate of growth in the teeth. The average rate of dentinogenesis for all the study animals is 17.96 microm/day. Results show that the rate of dentinogenesis is not significantly affected by the interaction of hormone and dietary supplementation.

  7. Role of mitochondria in programmed cell death mediated by arachidonic acid-derived eicosanoids. (United States)

    Yin, Huiyong; Zhou, Yunhua; Zhu, Mingjiang; Hou, Sarina; Li, Zi; Zhong, Huiqin; Lu, Jianhong; Meng, Tao; Wang, Junhong; Xia, Lin; Xu, Yue; Wu, Yuncheng


    Arachidonic acid-derived eicosanoids from cyclooxygenases, lipoxygenases, and cytochrome P450 are important lipid mediators involved in numerous homeostatic and pathophysiological processes. Most eicosanoids act primarily on their respective cell surface G-protein coupled receptors to elicit downstream signaling in an autocrine and paracrine fashion. Emerging evidence indicates that these hormones are also critical in apoptosis in a cell/tissue specific manner. In this review, we summarize the formation of eicosanoids and their roles as mediators in apoptosis, specifically on the roles of mitochondria in mediating these events and the signaling pathways involved. The biological relevance of eicosanoid-mediated apoptosis is also discussed.

  8. Glycerol-3-phosphate acyltransferase-2 is expressed in spermatic germ cells and incorporates arachidonic acid into triacylglycerols.

    Directory of Open Access Journals (Sweden)

    Elizabeth R Cattaneo

    Full Text Available BACKGROUND: De novo glycerolipid synthesis begins with the acylation of glycerol-3 phosphate catalyzed by glycerol-3-phosphate acyltransferase (GPAT. In mammals, at least four GPAT isoforms have been described, differing in their cell and tissue locations and sensitivity to sulfhydryl reagents. In this work we show that mitochondrial GPAT2 overexpression in CHO-K1 cells increased TAG content and both GPAT and AGPAT activities 2-fold with arachidonoyl-CoA as a substrate, indicating specificity for this fatty acid. METHODS AND RESULTS: Incubation of GPAT2-transfected CHO-K1 cells with [1-(14C]arachidonate for 3 h increased incorporation of [(14C]arachidonate into TAG by 40%. Consistently, arachidonic acid was present in the TAG fraction of cells that overexpressed GPAT2, but not in control cells, corroborating GPAT2's role in synthesizing TAG that is rich in arachidonic acid. In rat and mouse testis, Gpat2 mRNA was expressed only in primary spermatocytes; the protein was also detected in late stages of spermatogenesis. During rat sexual maturation, both the testicular TAG content and the arachidonic acid content in the TAG fraction peaked at 30 d, matching the highest expression of Gpat2 mRNA and protein. CONCLUSIONS: These results strongly suggest that GPAT2 expression is linked to arachidonoyl-CoA incorporation into TAG in spermatogenic germ cells.

  9. Arachidonic and eicosapentaenoic acids in Araucariaceae, a unique feature among seed plants

    Directory of Open Access Journals (Sweden)

    Wolff Robert L.


    Full Text Available It is generally admitted that seed plants (spermaphytes are unable to synthesize either arachidonic or eicosapentaenoic acids (AA and EPA, the classic essential fatty acids in animals. We give here chromatographic and spectrometric data showing that species from the primitive family Araucariaceae (gymnosperms are able to synthesize AA and/or EPA in their seeds and leaves. Agathis robusta, in particular, contains AA and EPA in small amounts in its seeds, with no D5-unsaturated polymethylene-interrupted fatty acids (D5-UPIFA with 18 carbon atoms, whereas Araucaria spp. contain both AA and C18 D5-UPIFA. In both species, D5-UPIFA with 20 carbon atoms are present as in all other Coniferophytes. All metabolic intermediates necessary for the biosynthesis of AA and/or EPA have been characterized in Araucariaceae seeds. The relevance of these observations is discussed with regard to the phylogeny of Coniferophytes.

  10. [The role of arachidonic acid metabolites in the regulation of renal function and pathogenesis of hypertension]. (United States)

    Certíková Chábová, V


    Eicosanoids are twenty-carbon compounds derived from arachidonic acid. Lipoxygenases, cyclooxygenases and cytochrome P-450 enzymes contribute to their synthesis. Our review is focused on prostaglandins, leucotrienes, lipoxins, hepoxilins, hydroxyeicosatetraenoic acids, and epoxyeicosatrienoic acids. Most of these compounds have multiple functions and they also participate in blood pressure regulation and excretion of water and solutes in the kidney. They have some roles in the patogenesis of kidney disease, too. Both experimental models (mainly geneticaly modified mice and rats) and human epidemiological and genetical studies are used in the investigation of eicosanoid physiological and patophysiological functions. New information about their enzymatic regulations and receptors have already resulted in the development of new drugs, mainly antiasthmatics, but further investigation should bring about new results in the treatment of hypertension and other cardiovascular and renal diseases.

  11. Equine tracheal epithelial membrane strips - An alternate method for examining epithelial cell arachidonic acid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Gray, P.R.; Derksen, F.J.; Robinson, N.E.; Peter-Golden, M.L. (Michigan State Univ., East Lansing (United States) Univ. of Michigan, Ann Arbor (United States))


    Arachidonic acid metabolism by tracheal epithelium can be studied using enzymatically dispersed cell suspensions or cell cultures. Both techniques require considerable tissue disruption and manipulation and may not accurately represent in vivo activity. The authors have developed an alternate method for obtaining strips of equine tracheal epithelium without enzymatic digestion. In the horse, a prominent elastic lamina supports the tracheal epithelium. By physical splitting this lamina, they obtained strips ({le}12 x 1.5 cm) of pseudostratified columnar epithelium attached to a layer of elastic tissue 30-100 {mu}m thick. Epithelial strips (1.2 x 0.5 cm) were attached to plexiglass rods and incubated with ({sup 3}H)arachidonic acid in M199 medium (0.5 {mu}Ci/ml) for 24 hours at 37C. The strips incorporated 36{+-}4% (mean {+-} SEM) of the total radioactivity and released 8.0{+-}1.2% of incorporated radioactivity when stimulated by 5.0 {mu}M calcium ionophore A23187. The extracted supernatant was processed using HPLC, resulting in peaks of radioactivity that co-eluted with authentic PGE{sub 2}, PGF{sub 2}{alpha}, and 12-HETE standards. The greatest activity corresponded to the PGE{sub 2} and PGF{sub 2}{alpha} standards, which is a similar pattern to that reported for cultured human tracheal epithelium.

  12. The target of arachidonic acid pathway is a new anticancer strategy for human prostate cancer

    Directory of Open Access Journals (Sweden)

    Masahide Matsuyama


    Full Text Available Masahide Matsuyama, Rikio YoshimuraDepartment of Urology, Osaka City University Graduate School of Medicine, Osaka, JapanAbstract: Recent epidemiological studies and animal experiments have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs reduce the incidence of colorectal carcinoma. Cyclooxygenase (COX is the principal target of NSAIDs. COX is the first oxidase in the process of prostaglandin production from arachidonic acid. COX enzyme may be involved in the initiation and/or the promotion of carcinogenesis due to NSAIDs inhibition of COX. Lipoxygenase (LOX is also an initial enzyme in the pathway for producing leukotrienes from arachidonic acid. Similar to COX, LOX enzyme may also be involved in the initiation and/or promotion of carcinogenesis. Peroxisome proliferator activator-receptor (PPAR-γ is a ligand-activated transcriptional factor belonging to the steroid receptor superfamily. PPAR-γ plays a role in both adipocyte differentiation and carcinogenesis. PPAR-γ is one target for cell growth modulation of NSAIDs. In this review, we report the expression of COX-2, LOX and PPAR-γ in human prostate cancer tissues as well as the effects of COX-2 and LOX inhibitors and PPAR-γ ligand.Keywords: cyclooxygenase, lipoxygenase, peroxisome proliferator activator-receptor-γ, prostate cancer

  13. Arachidonic acid metabolism in the platelets and neutrophils of diabetic rabbit and human subjects

    Energy Technology Data Exchange (ETDEWEB)

    Greco, N.J.


    An alteration of arachidonic acid metabolism to prostaglandins and leukotrienes from platelets and polymorphonuclear leukocytes respectively is evident in subjects with diabetes mellitus. There is evidence of altered platelet/vascular wall interactions in diabetes mellitus and evidence that polymorphonuclear leukocytes influence the vascular walls. Theories on the pathogenesis of atherosclerosis include both blood cells. Platelet hypersensitivity is evident in those platelets from the alloxan-induced diabetic rabbit either suspended in plasma or buffer. Arachidonic acid- and collagen-induced platelet aggregation, release of /sup 14/serotonin, and T x B/sub 2/ and 12-HETE production is enhanced when responses of diabetic platelets are compared to control platelets. Control rabbit neutrophils produce more LTB/sub 4/, LTB/sub 4/ isomers and 5-HETE than diabetic rabbits neutrophils. Decreased synthesis from diabetic rabbit neutrophils is not explained by increased catabolism of LTB/sub 4/, reesterification of 5-HETE, or increased eicosanoid formation. These experiments demonstrate both platelet and neutrophil dysfunction in diabetic subjects. Because of the involvement of these cells in regulating circulatory homeostatis, abnormal behavior could aggravate the atherosclerotic process. Platelet and neutrophil dysfunctions are noted before macroscopic vascular lesions are apparent suggesting an important role in the pathogenesis of atherosclerosis.

  14. Regulation of the arachidonic acid-stimulated respiratory burst in neutrophils by intra- cellular and extracellular calcium

    Institute of Scientific and Technical Information of China (English)


    The respiratory burst is an important physiological function ofthe neutrophils in killing the bacteria invading in human body. We used chemiluminescence method to measure the exogenous arachidonic acid-stimulated respiratory burst, and measured the cytosolic free calcium concentration in neutrophils by the fluorescence method. It was found that, on one hand, the arachidonic acid-stimulated respiratory burst was enhanced by elevating the cytosolic free calcium concentration in neutrophils with a potent endomembrane Ca2+-ATPase inhibitor, Thapsgargin; on the other hand, chelating the intracellular or extracellular calcium by EGTA or BAPTA inhibited the respiratory burst. Results showed that calcium plays an important regulatory role in the signaling pathway involved in the exogenous arachidonic acid-stimulated respiratory burst of neutrophils.

  15. Inhibition by amiloride and by Na-depletion of A23187-stimulated arachidonic acid and histamine release from rat mast cells

    DEFF Research Database (Denmark)

    Linnebjerg, H.; Hansen, Harald S.; Jensen, B.


    Rat peritoneal mast cells, labelled with [C]arachidonic acid, released histamine and [C]arachidonic acid upon the addition of A23187. The release induced by low concentrations of A23187 was suppressed by removal of extracellular Na and by addition of the Na/H exchange inhibitor, amiloride. Addition...

  16. Surfactant-induced alteration of arachidonic acid metabolism of mammalian cells in culture. (United States)

    De Leo, V A; Harber, L C; Kong, B M; De Salva, S J


    Primary irritancy in human and animal skin is characterized by an inflammatory reaction mediated, in part, by membrane-derived arachidonate metabolites. One of the mechanisms of this reaction was investigated in cultured mammalian cells using three surfactants: linear alkyl benzene sulfonate (LAS), alkyl ethoxylate sulfate (AEOS), and TWEEN 20. These compounds listed in order in vivo irritancy are LAS greater than AEOS greater than TWEEN 20. Each of these compounds was studied in C3H-10T1/2 cells and human keratinocytes which had been prelabeled with 3H-labeled arachidonic acid (AA). After labeling, media were removed, cells were washed, and fresh media with or without surfactant were added. Cells were then incubated for 2 hr, media were removed and centrifuged, and an aliquot was assayed by liquid scintillation for release of label. In C3H-10T1/2 cells LAS and AEOS in 5-50 microM concentration stimulated 2 to 10 times the release of [3H]AA as compared to controls. In contrast, concentrations of 50-100 microM of TWEEN were required to release [3H]AA. With keratinocytes the same rank order of surfactant concentrations necessary for release was obtained as found with C3H-10T1/2 cells. High-performance liquid chromatography of media extracts of both cell systems revealed surfactant stimulation of the production of cyclooxygenase AA metabolites. These results confirm the induction of release by primary irritants of fatty acid groups from membrane phospholipids. Subsequent metabolism of these fatty acid groups are an integral part of the primary irritant response. Data presented with three known irritants in this in vitro model show a direct correlation with in vivo studies.

  17. Arachidonic Acid Derivatives and Their Role in Peripheral Nerve Degeneration and Regeneration

    Directory of Open Access Journals (Sweden)

    Carlos Rodrigo Camara-Lemarroy


    Full Text Available After peripheral nerve injury, a process of axonal degradation, debris clearance, and subsequent regeneration is initiated by complex local signaling, called Wallerian degeneration (WD. This process is in part mediated by neuroglia as well as infiltrating inflammatory cells and regulated by inflammatory mediators such as cytokines, chemokines, and the activation of transcription factors also related to the inflammatory response. Part of this neuroimmune signaling is mediated by the innate immune system, including arachidonic acid (AA derivatives such as prostaglandins and leukotrienes. The enzymes responsible for their production, cyclooxygenases and lipooxygenases, also participate in nerve degeneration and regeneration. The interactions between signals for nerve regeneration and neuroinflammation go all the way down to the molecular level. In this paper, we discuss the role that AA derivatives might play during WD and nerve regeneration, and the therapeutic possibilities that arise.

  18. Arachidonic Acid Derivatives and Their Role in Peripheral Nerve Degeneration and Regeneration (United States)

    Camara-Lemarroy, Carlos Rodrigo; Gonzalez-Moreno, Emmanuel Irineo; Guzman-de la Garza, Francisco Javier; Fernandez-Garza, Nancy Esthela


    After peripheral nerve injury, a process of axonal degradation, debris clearance, and subsequent regeneration is initiated by complex local signaling, called Wallerian degeneration (WD). This process is in part mediated by neuroglia as well as infiltrating inflammatory cells and regulated by inflammatory mediators such as cytokines, chemokines, and the activation of transcription factors also related to the inflammatory response. Part of this neuroimmune signaling is mediated by the innate immune system, including arachidonic acid (AA) derivatives such as prostaglandins and leukotrienes. The enzymes responsible for their production, cyclooxygenases and lipooxygenases, also participate in nerve degeneration and regeneration. The interactions between signals for nerve regeneration and neuroinflammation go all the way down to the molecular level. In this paper, we discuss the role that AA derivatives might play during WD and nerve regeneration, and the therapeutic possibilities that arise. PMID:22997489

  19. Ozone toxicity: hormone-like oxidation products from arachidonic acid by ozone-catalyzed autoxidation

    Energy Technology Data Exchange (ETDEWEB)

    Roycroft, J.H.; Cunter, W.B.; Menzel, D.B.


    The effects of peroxidation by ozone on the activity of arachidonic acid (AA) with and without vitamin E, on the initiation of human platelet aggregation, and on the contraction of superfused smooth muscle strips, are described. AA was rapidly oxidized by a stream of air containing 2 ppm of ozone to peroxides having biological activity similar to prostaglandin endoperoxides. Ozone-formed AA peroxides contracted both rabbit aortic strips and rat fundus strips in the presence of indomethacin and vasoactive hormones at doses comparable to naturally formed prostaglandin endoperoxides. Vitamin E had no effect on the activity of AA peroxides once formed. Ozone-formed AA peroxides also aggregated human platelets in platelet rich plasma, but this activity was blocked by the addition of indomethacin. (2 diagrams, 3 graphs, 8 references)

  20. Arachidonic acid modulates hippocampal calcium current via protein kinase C and oxygen radicals. (United States)

    Keyser, D O; Alger, B E


    Arachidonic acid (AA) is a second messenger liberated via receptor activation of phospholipase A2 or diacylglycerol-lipase. We used whole-cell voltage clamp of acutely isolated hippocampal CA1 pyramidal cells to investigate the hypothesis that AA modulates Ca2+ channel current (ICa) via activation of protein kinase C (PKC) and generation of free radicals. AA depressed ICa in a dose- and time-dependent manner similar to that previously reported for the action of phorbol esters on ICa. A similar depression was seen with a xanthine-based free radical generating system. The specific PKC inhibitor PKCI (19-36), the protein kinase inhibitor H-7, and the superoxide free radical scavenger SOD each blocked ICa depression by 70%-80%. Complete block of the AA response occurred when SOD was used simultaneously with a PKC inhibitor. These data suggest that PKC and free radicals play a role in AA-induced suppression of ICa.

  1. Neutrophil chemotaxis and arachidonic acid metabolism are not linked: evidence from metal ion probe studies

    Energy Technology Data Exchange (ETDEWEB)

    Turner, S.R.; Turner, R.A.; Smith, D.M.; Johnson, J.A.


    Heavy metal ions can inhibit arachidonic acid (AA) metabolism protect against ionophore cytotoxicity (ibid) and inhibit neutrophil chemotaxis. In this study they used Au/sup 3 +/, Zn/sup 2 +/, Cr/sup 3 +/, Mn/sup 2 +/ and Cu/sup 2 +/ as probes of the interrelationships among AA metabolism, ionophore-mediated cytotoxicity, and chemotaxis. Phospholipid deacylation was measured in ionophore-treated cells prelabeled with /sup 3/H-AA. Eicosanoid release from ionophore-treated cells was monitored by radioimmunoassay. Cytoprotection was quantitated as ability to exclude trypan blue. Chemotaxis toward f-met-leu-phe was measured by leading front analysis. The results imply that metal ions attenuate ionophore cytotoxicity by blocking phospholipid deacylation and eicosanoid release. In contrast to previous reports, no correlation between AA metabolism and chemotaxis was demonstrated, suggesting that these 2 processes are not linked.

  2. Eicosanoids Derived From Arachidonic Acid and Their Family Prostaglandins and Cyclooxygenase in Psychiatric Disorders. (United States)

    Yui, Kunio; Imataka, George; Nakamura, Hiroyuki; Ohara, Naoki; Naito, Yukiko


    Arachidonic acid (AA)-derived lipid mediators are called eicosanoids. Eicosanoids have emerged as key regulators of a wide variety of physiological responses and pathological processes, and control important cellular processes. AA can be converted into biologically active compounds by metabolism by cyclooxygenases (COX). Beneficial effect of COX-2 inhibitor celecoxib add-on therapy has been reported in early stage of schizophrenia. Moreover, add-on treatment of celecoxib attenuated refractory depression and bipolar depression. Further, the COX/prostaglandin E pathway play an important role in synaptic plasticity and may be included in pathophysiology in autism spectrum disorders (ASD). In this regard, plasma transferrin, which is an iron mediator related to eicosanoid signaling, may be related to social impairment of ASD. COX-2 is typically induced by inflammatory stimuli in the majority of tissues, and the only isoform responsible for propagating the inflammatory response. Thus, COX-2 inhibitors considered as the best target for Alzheimer's disease.

  3. Phenylethanoids in the herb of Plantago lanceolata and inhibitory effect on arachidonic acid-induced mouse ear edema. (United States)

    Murai, M; Tamayama, Y; Nishibe, S


    The five phenylethanoids, acteoside (1), cistanoside F (2), lavandulifolioside (3), plantamajoside (4) and isoacteoside (5) were isolated from the herb of Plantago lanceolata L. (Plantaginaceae). Compounds 1, the major phenylethanoid in the herb of P. lanceolata L., and 4, the major phenylethanoid in the herb of P. asiatica L., showed inhibitory effects on arachidonic acid-induced mouse ear edema.

  4. Polymorphisms in the genes involved in the arachidonic acid-pathway, fish consumption and the risk of colorectal cancer.

    NARCIS (Netherlands)

    Siezen, Christine L E; Bueno-de-Mesquita, H Bas; Peeters, Petra H M; Kram, Nicolien R; Doeselaar, Marina van; Kranen, Henk J van


    The objective of this study on colorectal cancer was to investigate the associations between SNPs in the genes involved in the arachidonic acid (AA)-pathway, their haplotypes and colorectal cancer. Moreover, interactions between SNPs and fish consumption were considered. In this study, a total of 50

  5. The Polyunsaturated Fatty Acids Arachidonic Acid and Docosahexaenoic Acid Induce Mouse Dendritic Cells Maturation but Reduce T-Cell Responses In Vitro. (United States)

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


    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 Violet low) 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.

  6. Calcium-dependent phospholipid catabolism and arachidonic acid mobilization in cerebral minces

    Energy Technology Data Exchange (ETDEWEB)

    Damron, D.S.; Dorman, R.V. (Kent State Univ., OH (USA))


    Cerebral minces were used to investigate the role of calcium influx on trauma-induced alterations of brain lipid metabolism. Cerebral phospholipids, nonpolar lipids, and free fatty acids were radiolabeled in vivo with ({sup 3}H)arachidonic acid. Tissue incubation stimulated the time-dependent catabolism of choline and inositol glycerophospholipids, and resulted in the accumulation of ({sup 3}H)free fatty acids. These effects were attenuated in Ca{sup 2}{sup +}-free incubations, and when EGTA or verapamil were present. The inhibition of calcium influx also reduced the labeling of diglycerides, whereas ethanolamine and serine glycerophospholipids were not affected by incubation or treatments. Replacing Ca{sup 2}{sup +} with other cations also attenuated the incubation-dependent alterations in lipid metabolism. However, only cadmium was able to compete with calcium and reduce the accumulation of ({sup 3}H)free fatty acids. It appeared that about half of the observed phospholipid catabolism was dependent on Ca{sup 2}{sup +} influx and that at least 80% of the ({sup 3}H)free fatty acid accumulation required calcium.

  7. The increased level of COX-dependent arachidonic acid metabolism in blood platelets from secondary progressive multiple sclerosis patients. (United States)

    Morel, Agnieszka; Miller, Elzbieta; Bijak, Michal; Saluk, Joanna


    Platelet activation is increasingly postulated as a possible component of the pathogenesis of multiple sclerosis (MS), especially due to the increased risk of cardiovascular events in MS. Arachidonic acid cascade metabolized by cyclooxygenase (COX) is a key pathway of platelet activation. The aim of our study was to investigate the COX-dependent arachidonic acid metabolic pathway in blood platelets from secondary progressive multiple sclerosis (SP MS) patients. The blood samples were obtained from 50 patients (man n = 22; female n = 28), suffering from SP MS, diagnosed according to the revised McDonald criteria. Platelet aggregation was measured in platelet-rich plasma after arachidonic acid stimulation. The level of COX activity and thromboxane B2 concentration were determined by ELISA method. Lipid peroxidation was assessed by measuring the level of malondialdehyde. The results were compared with a control group of healthy volunteers. We found that blood platelets obtained from SP MS patients were more sensitive to arachidonic acid and their response measured as platelet aggregation was stronger (about 14 %) relative to control. We also observed a significantly increased activity of COX (about 40 %) and synthesis of thromboxane B2 (about 113 %). The generation of malondialdehyde as a marker of lipid peroxidation was about 10 % higher in SP MS than in control. Cyclooxygenase-dependent arachidonic acid metabolism is significantly increased in blood platelets of patients with SP MS. Future clinical studies are required to recommend the use of low-dose aspirin, and possibly other COX inhibitors in the prevention of cardiovascular risk in MS.

  8. Lipid characterization of an arachidonic acid-rich oil producing fungus Mortierella alpina

    Institute of Scientific and Technical Information of China (English)

    Wenjia Wu; Jiacheng Yan; Xiaojun Ji; Xin Zhang; Jingsheng Shang; Lina Sun; Lujing Ren; He Huang


    Mortierel a alpina has been considered as the most effective producer of arachidonic acid (ARA)-rich oil. It was found that several methods could improve the percentage of ARA in total lipids successful y, as they activated the desaturation system on the endoplasmic reticulum. Additionally, in M. alpina the ARA exists in several forms, such as triacylglycerol (TAG), and diacylglycerol (DAG). These forms are caused by different acyltransferases and they determine the nutrient value of the microbial oil. However, few works revealed de-tailed fatty acid distribution among lipid classes, which to some extent impeded the accurate regulation in ARA accumulation. Herein, this paper gives information on the accumulation process of main lipid classes and the changes of fatty acid composition in these lipids during ARA accumulation period in M. alpina. The result dem-onstrates that TAG was the dominant component of the total lipids, and it is the main form for ARA storage. The ARA enrichment stage occurred during 168–192 h when the amount of total lipids maintained steady. Further analysis indicated that the newly formed ARA-TAG might come from the incorporation and modification of sat-urated and monounsaturated fatty acids in other lipid classes. This work could be helpful for further optimization of ARA-rich TAG production.

  9. Arachidonic acid accumulates in the stromal macrophages during thymus involution in diabetes. (United States)

    Gruia, Alexandra T; Barbu-Tudoran, Lucian; Mic, Ani A; Ordodi, Valentin L; Paunescu, Virgil; Mic, Felix A


    Diabetes is a debilitating disease with chronic evolution that affects many tissues and organs over its course. Thymus is an organ that is affected early after the onset of diabetes, gradually involuting until it loses most of its thymocyte populations. We show evidence of accumulating free fatty acids with generation of eicosanoids in the diabetic thymus and we present a possible mechanism for the involution of the organ during the disease. Young rats were injected with streptozotocin and their thymuses examined for cell death by flow cytometry and TUNEL reaction. Accumulation of lipids in the diabetic thymus was investigated by histology and electron microscopy. The identity and quantitation of accumulating lipids was done with gas chromatography-mass spectrometry and liquid chromatography. The expression and dynamics of the enzymes were monitored via immunohistochemistry. Diabetes causes thymus involution by elevating the thymocyte apoptosis. Exposure of thymocytes to elevated concentration of glucose causes apoptosis. After the onset of diabetes, there is a gradual accumulation of free fatty acids in the stromal macrophages including arachidonic acid, the substrate for eicosanoids. The eicosanoids do not cause thymocyte apoptosis but administration of a cyclooxygenase inhibitor reduces the staining for ED1, a macrophage marker whose intensity correlates with phagocytic activity. Diabetes causes thymus involution that is accompanied by accumulation of free fatty acids in the thymic macrophages. Excess glucose is able to induce thymocyte apoptosis but eicosanoids are involved in the chemoattraction of macrophage to remove the dead thymocytes.

  10. Synergy by secretory phospholipase A2 and glutamate on inducing cell death and sustained arachidonic acid metabolic changes in primary cortical neuronal cultures

    DEFF Research Database (Denmark)

    Kolko, M; DeCoster, M A; de Turco, E B


    Secretory and cytosolic phospholipases A2 (sPLA2 and cPLA2) may contribute to the release of arachidonic acid and other bioactive lipids, which are modulators of synaptic function. In primary cortical neuron cultures, neurotoxic cell death and [3H]arachidonate metabolism was studied after adding...


    Lizogub, V G; Zavalska, T V; Merkulova, I O; Bryuzgina, T S


    Erythrocytes and platelets phospholipid membranes fatty acid spectrum was detected in coronary heart disease and atrial fibrillation patients and in patients with coronary heart disease without atrial fibrillation. 87 patients were investigated. Significant decrease in the arachidonic acid relative content in coronary heart disease patients compared with healthy individuals was related. As well as a significant decrease in the arachidonic acid relative content in coronary heart disease and atrial fibrillation patients compared with coronary heart disease patients without atrial fibrillation was related too. These dates may indicate that decreasing relative content arachidonic acid can be possible pathogenetic link in the development of arrhythmias.

  12. Arachidonic acid mediates the formation of abundant alpha-helical multimers of alpha-synuclein (United States)

    Iljina, Marija; Tosatto, Laura; Choi, Minee L.; Sang, Jason C.; Ye, Yu; Hughes, Craig D.; Bryant, Clare E.; Gandhi, Sonia; Klenerman, David


    The protein alpha-synuclein (αS) self-assembles into toxic beta-sheet aggregates in Parkinson’s disease, while it is proposed that αS forms soluble alpha-helical multimers in healthy neurons. Here, we have made αS multimers in vitro using arachidonic acid (ARA), one of the most abundant fatty acids in the brain, and characterized them by a combination of bulk experiments and single-molecule Fӧrster resonance energy transfer (sm-FRET) measurements. The data suggest that ARA-induced oligomers are alpha-helical, resistant to fibril formation, more prone to disaggregation, enzymatic digestion and degradation by the 26S proteasome, and lead to lower neuronal damage and reduced activation of microglia compared to the oligomers formed in the absence of ARA. These multimers can be formed at physiologically-relevant concentrations, and pathological mutants of αS form less multimers than wild-type αS. Our work provides strong biophysical evidence for the formation of alpha-helical multimers of αS in the presence of a biologically relevant fatty acid, which may have a protective role with respect to the generation of beta-sheet toxic structures during αS fibrillation.

  13. Ethanolic extract of Piper betle Linn. leaves reduces nociception via modulation of arachidonic acid pathway

    Directory of Open Access Journals (Sweden)

    Soumita De


    Full Text Available Objectives: The objective of this study was to evaluate the peripheral analgesic effect of Piper betle leaf extract (PBE along with establishing its putative mechanism of action. Materials and Methods: Male Swiss albino mice after pre-treatment (1 h with different doses of PBE were injected 0.8% (v/v acetic acid i.p.; the onset and number of writhes were noted up to 15 min. To evaluate the mechanism of action, the murine peritoneal exudate was incubated with PBE for 1 h, followed by exposure to arachidonic acid (AA and generation of reactive oxygen species (ROS was measured by flow cytometry using 2′,7′-dichlorodihydrofluorescein diacetate. Results: PBE in a dose dependent manner significantly reduced acetic acid induced writhing response in mice (P < 0.001. In peritoneal exudates, PBE significantly inhibited AA induced generation of ROS, P < 0.01. Conclusions: The present study indicates that PBE has promising analgesic activity, worthy of future pharmacological consideration.

  14. Effects of organometals on cellular signaling. I. Influence of metabolic inhibitors on metal-induced arachidonic acid liberation.



    Organic lead and tin compounds stimulate an increase of free arachidonic acid (AA) in HL-60 cells. This fatty acid is involved in numerous health problems and physiological mechanisms. Three major pathways result in a liberation of AA from membrane phospholipids and there is evidence that G-proteins serve as couplers within all three pathways. Therefore we investigated the influence of pertussis toxin (PT) on the organometallic-induced AA liberation. The effect of all studied compounds (organ...

  15. The effect of reactive oxygen species on the synthesis of prostanoids from arachidonic acid. (United States)

    Korbecki, J; Baranowska-Bosiacka, I; Gutowska, I; Chlubek, D


    Reactive oxygen species (ROS), such as hydrogen peroxide, superoxide anion radical or hydroxyl radical, play an important role in inflammation processes as well as in transduction of signals from receptors to interleukin -1β (IL-1β), tumor necrosis factor α (TNF-α) or lipopolysaccharides (LPS). NADPH oxidase increases the ROS levels, leading to inactivation of protein phosphatase 1 (PP1), protein phosphatase 2A (PP2A) and protein tyrosine phosphatase (PTP): MAPK phosphatase 1 (MKP-1). Inactivation of phosphatases results in activation of mitogen-activated protein kinase (MAPK) cascades: c-Jun N-terminal kinase (JNK), p38 and extracellular signal-regulated kinase (Erk), which, in turn, activate cytosolic phospholipase A₂ (cPLA₂). ROS cause cytoplasmic calcium influx by activation of phospholipase C (PLC) and phosphorylation of IP₃-sensitive calcium channels. ROS activate nuclear factor κB (NF-κB) via IκB kinase (IKK) through phosphoinositide 3-kinase (PI3K), tumor suppressor phosphatase and tensin homolog (PTEN) and protein kinase B (Akt/PKB) or NF-κB-inducing kinase (NIK). IKK phosphorylates NF-κB α subunit (IκBα) at Ser³². Oxidative stress inactivates NIK and IκB kinase γ subunit/NF-κB essential modulator (IKKγ/NEMO), which might cause activation of NF-κB that is independent on IKK and inhibitor of IκBα degradation, including phosphorylation of Tyr⁴² at IκBα by c-Src and spleen tyrosine kinase (Syk), phosphorylation of the domain rich in proline, glutamic acid, serine and threonine (PEST) sequence by casein kinase II and inactivation of protein tyrosine phosphatase 1B (PTP1B). NF-κB and MAPK cascades-activated transcription factor activator protein 1 (AP-1) and CREB-binding protein (CBP/p300) lead to expression of cytosolic phospholipase A₂ (cPLA₂), cyclooxygenase-2 (COX-2) and membrane-bound prostaglandin E synthase 1 (mPGES-1), and thus to increased release of arachidonic acid and production of prostaglandins, particularly

  16. Development of a defined medium for arachidonic acid production by Mortierella alpina using a visualization method. (United States)

    Liu, Xin; Ji, Xiaojun; Zhang, Hongman; Fu, Ninghua; Yan, Liexiang; Deng, Zhongtao; Huang, He


    Defined medium for arachidonic acid (ARA) production by Mortierella alpina was optimized for its metabolomics study. For this purpose, a visualization method (VM) was applied for the first time. Experiments were designed according to the uniform design with four factors (concentrations of glucose, NaNO(3), KH(2)PO(4) and MgSO(4)·7H(2)O) for each at nine levels. Dry cell weight (DCW), ARA yield in DCW [percent (w/w)] and ARA content in total fatty acids [percent (w/w)] were considered as the three objectives. Optimization of single-objective function and multi-objective function of two objectives and three objectives was attempted. Optimal DCW, ARA yield and ARA content were predicted to occur in a medium that contained (grams per litre): glucose 35, NaNO(3) 1, KH(2)PO(4) 7.5 and MgSO(4)·7H(2)O 2.6. Upon verification, the average tested DCW (12.95 g/l), ARA yield (18.89 %) and ARA content (42.36 %) were fairly close to the predicted values (12.88 g/l, 9.68 % and 35.57 %, respectively). Moreover, DCW, ARA yield and ARA content from the optimum medium increased by 35.68, 47.23 and 30.90 % compared with control, respectively, indicating that VM had succeeded in exploiting the biomass growth and ARA production by M. alpina.

  17. Cell survival signalling through PPARδ and arachidonic acid metabolites in neuroblastoma.

    Directory of Open Access Journals (Sweden)

    Emma Bell

    Full Text Available Retinoic acid (RA has paradoxical effects on cancer cells: promoting cell death, differentiation and cell cycle arrest, or cell survival and proliferation. Arachidonic acid (AA release occurs in response to RA treatment and, therefore, AA and its downstream metabolites may be involved in cell survival signalling. To test this, we inhibited phospholipase A2-mediated AA release, cyclooxygenases and lipoxygenases with small-molecule inhibitors to determine if this would sensitise cells to cell death after RA treatment. The data suggest that, in response to RA, phospholipase A2-mediated release of AA and subsequent metabolism by lipoxygenases is important for cell survival. Evidence from gene expression reporter assays and PPARδ knockdown suggests that lipoxygenase metabolites activate PPARδ. The involvement of PPARδ in cell survival is supported by results of experiments with the PPARδ inhibitor GSK0660 and siRNA-mediated knockdown. Quantitative reverse transcriptase PCR studies demonstrated that inhibition of 5-lipoxygenase after RA treatment resulted in a strong up-regulation of mRNA for PPARδ2, a putative inhibitory PPARδ isoform. Over-expression of PPARδ2 using a tetracycline-inducible system in neuroblastoma cells reduced proliferation and induced cell death. These data provide evidence linking lipoxygenases and PPARδ in a cell survival-signalling mechanism and suggest new drug-development targets for malignant and hyper-proliferative diseases.

  18. 2-hydroxy arachidonic acid: a new non-steroidal anti-inflammatory drug.

    Directory of Open Access Journals (Sweden)

    Daniel H Lopez

    Full Text Available BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs are a family of COX1 and COX2 inhibitors used to reduce the synthesis of pro-inflammatory mediators. In addition, inflammation often leads to a harmful generation of nitric oxide. Efforts are being done in discovering safer NSAIDs molecules capable of inhibiting the synthesis of pro-inflammatory lipid mediators and nitric oxide to reduce the side effects associated with long term therapies. METHODOLOGY/PRINCIPAL FINDINGS: The analogue of arachidonic acid (AA, 2-hydroxy-arachidonic acid (2OAA, was designed to inhibit the activities of COX1 and COX2 and it was predicted to have similar binding energies as AA for the catalytic sites of COX1 and COX2. The interaction of AA and 2OAA with COX1 and COX2 was investigated calculating the free energy of binding and the Fukui function. Toxicity was determined in mouse microglial BV-2 cells. COX1 and COX2 (PGH2 production activities were measured in vitro. COX1 and COX2 expression in human macrophage-like U937 cells were carried out by Western blot, immunocytochemistry and RT-PCR analysis. NO production (Griess method and iNOS (Western blot were determined in mouse microglial BV-2 cells. The comparative efficacy of 2OAA, ibuprofen and cortisone in lowering TNF-α serum levels was determined in C57BL6/J mice challenged with LPS. We show that the presence of the -OH group reduces the likelihood of 2OAA being subjected to H* abstraction in COX, without altering significantly the free energy of binding. The 2OAA inhibited COX1 and COX2 activities and the expression of COX2 in human U937 derived macrophages challenged with LPS. In addition, 2OAA inhibited iNOS expression and the production of NO in BV-2 microglial cells. Finally, oral administration of 2OAA decreased the plasma TNF-α levels in vivo. CONCLUSION/SIGNIFICANCE: These findings demonstrate the potential of 2OAA as a NSAID.

  19. The effects of xanthoangelol E on arachidonic acid metabolism in the gastric antral mucosa and platelet of the rabbit. (United States)

    Fujita, T; Sakuma, S; Sumiya, T; Nishida, H; Fujimoto, Y; Baba, K; Kozawa, M


    The effects of a new chalcone derivative, xanthoangelol E, isolated from Angelica keiskei Koidzumi, on arachidonic acid metabolism in the gastric antral mucosa and platelet of the rabbit were examined. When gastric antral mucosal slices were incubated with xanthoangelol E (0.05-1.0 mM), there was no significant effect on the production of prostaglandin (PG) E2, PGF2 alpha and their metabolites. On the other hand, this compound inhibited effectively the production of thromboxane B2 and 12-hydroxy-5,8,10-heptadecatrienoic acid from exogenous arachidonic acid in platelets, and the concentration required for 50% inhibition (IC50) was approximately 5 microM. The formation of 12-hydroxy-5,8,10,14-eicosatetraenoic acid was also reduced by this drug (IC50, 50 microM). These results suggest that xanthoangelol E has the potential to modulate arachidonic acid metabolism in platelets and that this action may participate in some pharmacological effect of the plant.

  20. Human prefrontal cortex phospholipids containing docosahexaenoic acid increase during normal adult aging, whereas those containing arachidonic acid decrease. (United States)

    Norris, Sarah E; Friedrich, Michael G; Mitchell, Todd W; Truscott, Roger J W; Else, Paul L


    Membrane phospholipids make up a substantial portion of the human brain, and changes in their amount and composition are thought to play a role in the pathogenesis of age-related neurodegenerative disease. Nevertheless, little is known about the changes that phospholipids undergo during normal adult aging. This study examined changes in phospholipid composition in the mitochondrial and microsomal membranes of human dorsolateral prefrontal cortex over the adult life span. The largest age-related changes were an increase in the abundance of both mitochondrial and microsomal phosphatidylserine 18:0_22:6 by approximately one-third from age 20 to 100 years and a 25% decrease in mitochondrial phosphatidylethanolamine 18:0_20:4. Generally, increases were seen with age in phospholipids containing docosahexaenoic acid across both membrane fractions, whereas phospholipids containing either arachidonic or adrenic acid decreased with age. These findings suggest a gradual change in membrane lipid composition over the adult life span.

  1. The biosynthesis of N-arachidonoyl dopamine (NADA), a putative endocannabinoid and endovanilloid, via conjugation of arachidonic acid with dopamine. (United States)

    Hu, Sherry Shu-Jung; Bradshaw, Heather B; Benton, Valery M; Chen, Jay Shih-Chieh; Huang, Susan M; Minassi, Alberto; Bisogno, Tiziana; Masuda, Kim; Tan, Bo; Roskoski, Robert; Cravatt, Benjamin F; Di Marzo, Vincenzo; Walker, J Michael


    N-arachidonoyl dopamine (NADA) is an endogenous ligand that activates the cannabinoid type 1 receptor and the transient receptor potential vanilloid type 1 channel. Two potential biosynthetic pathways for NADA have been proposed, though no conclusive evidence exists for either. The first is the direct conjugation of arachidonic acid with dopamine and the other is via metabolism of a putative N-arachidonoyl tyrosine (NA-tyrosine). In the present study we investigated these biosynthetic mechanisms and report that NADA synthesis requires TH in dopaminergic terminals; however, NA-tyrosine, which we identify here as an endogenous lipid, is not an intermediate. We show that NADA biosynthesis primarily occurs through an enzyme-mediated conjugation of arachidonic acid with dopamine. While this conjugation likely involves a complex of enzymes, our data suggest a direct involvement of fatty acid amide hydrolase in NADA biosynthesis either as a rate-limiting enzyme that liberates arachidonic acid from AEA, or as a conjugation enzyme, or both.

  2. Phospholipid, arachidonate and eicosanoid signaling in schizophrenia


    Messamore Erik; Yao Jeffrey K.


    This paper reviews the potential role of arachidonic acid in the pathophysiology of schizophrenia. We discuss how abnormal levels of arachidonic acid may arise, and how dysregulation of signaling molecules derived from it have the potential to disrupt not only dopamine signaling, but numerous other physiological processes associated with the illness. Pharmacological doses of niacin stimulate the release of arachidonic acid; and arachidonic acid-derived molecules in turn dilate blood vessels i...

  3. The effects of anaerobic training in serum lipids and arachidonic acid metabolites

    Directory of Open Access Journals (Sweden)



    Full Text Available Coronary arteries are subjected daily in high shear stress and manifest atherosclerosis very early in life in comparison to other arteries in the human body. Some factors that are implicated in the evolution and progress of this process are the concentration of lipids and arachidonic acid metabolites, such prostacyclin and thromboxane. It has been reported that those who participate in aerobic activities such as walking, cycling, jogging or brisk walking might have normal values of the mentioned chemical substances. On the other hand, it is reported that the effects of anaerobic and strength activities has negative effects on the vascular endothelium, which is essential for the maintenance of hemostatic balance and the local regulation of vascular tone.Therefore, even although extensive research has been conducted in this field, there are crucial gaps in our knowledge. Consequently, the purpose of this brief review is to describe what is known about the effects of anaerobic activities in which the competitive athletes have participated on the following blood parameters: Total cholesterol, triglycerides, high density lipoprotein cholesterol (HDL - C, low density lipoproteins cholesterol (LDL - C, prostacyclin & thromboxane.

  4. Shuffling the cards in signal transduction: Calcium, arachidonic acid and mechanosensitivity

    Institute of Scientific and Technical Information of China (English)

    Luca; Munaron


    Cell signaling is a very complex network of biochemical reactions triggered by a huge number of stimuli coming from the external medium. The function of any single signaling component depends not only on its own structure but also on its connections with other biomolecules. During prokaryotic-eukaryotic transition, the rearrangement of cell organization in terms of diffusional compartmentalization exerts a deep change in cell signaling functional potentiality. In this review I briefly introduce an intriguing ancient relationship between pathways involved in cell responses to chemical agonists (growth factors, nutrients, hormones) as well as to mechanical forces (stretch, osmotic changes). Some biomolecules (ion channels and enzymes) act as "hubs", thanks to their ability to be directly or indirectly chemically/mechanically co-regulated. In particular calcium signaling machinery and arachidonic acid metabolism are very ancient networks, already present before eukaryotic appearance. A number of molecular "hubs", including phospholipase A2 and some calcium channels, appear tightly interconnected in a cross regulation leading to the cellular response to chemical and mechanical stimulations.

  5. Activation of the central histaminergic system mediates arachidonic-acid-induced cardiovascular effects. (United States)

    Altinbas, Burcin; Topuz, Bora Burak; İlhan, Tuncay; Yilmaz, Mustafa Sertac; Erdost, Hatice; Yalcin, Murat


    The aim of this study was to explain the involvement of the central histaminergic system in arachidonic acid (AA)-induced cardiovascular effects in normotensive rats using hemodynamic, immunohistochemistry, and microdialysis studies. Intracerebroventricularly (i.c.v.) administered AA (0.25, 0.5, and 1.0 μmol) induced dose- and time-dependent increases in mean arterial pressure and decreased heart rate in conscious normotensive Sprague-Dawley rats. Central injection of AA (0.5 μmol) also increased posterior hypothalamic extracellular histamine levels and produced strong COX-1 but not COX-2 immunoreactivity in the posterior hypothalamus of rats. Moreover, the cardiovascular effects and COX-1 immunoreactivity in the posterior hypothalamus induced by AA (0.5 μmol; i.c.v.) were almost completely blocked by the H2 receptor antagonist ranitidine (50 and 100 nmol; i.c.v.) and partially blocked by the H1 receptor blocker chlorpheniramine (100 nmol; i.c.v.) and the H3-H4 receptor antagonist thioperamide (50 and 100 nmol; i.c.v.). In conclusion, these results indicate that centrally administered AA induces pressor and bradycardic responses in conscious rats. Moreover, we suggest that AA may activate histaminergic neurons and increase extracellular histamine levels, particularly in the posterior hypothalamus. Acting as a neurotransmitter, histamine is potentially involved in AA-induced cardiovascular effects under normotensive conditions.

  6. Effect of heavy metal ions on neutrophil arachidonic acid metabolism and chemotaxis

    Energy Technology Data Exchange (ETDEWEB)

    Smith, D.M.; Turner, S.R.; Johnson, J.A.; Turner, R.A.


    Heavy metal ions can inhibit arachidonic acid (AA) metabolism, protect against ionophore cytotoxicity (ibid) and inhibit neutrophil chemotaxis. In this study they used Au/sup +3/, Zn/sup +2/, Cr/sup +3/, Mn/sup +2/, and Cu/sup +2/ as probes of the interrelationships among AA metabolism, ionophore-mediated cytotoxicity, and chemotaxis. Phospholipid deacylation was measured in ionophore-treated cells prelabeled with /sup 3/H-AA. Eicosanoid release from ionophore-treated cells was monitored both qualitatively by thin-layer chromatography of /sup 3/H-AA metabolities and quantitatively by radioimmunoassay. Cytoprotection was quantitated as ability to exclude trypan blue. Chemotaxis toward f-Met-Leu-Phe was measured by leading front analysis. The results imply that metal ions attenuate ionophore cytotoxicity by blocking phospholipid deacylation and eicosanoid production. In contrast to previous reports, the data obtained using Au/sup +3/ and Cu/sup +2/ demonstrates no correlation between AA metabolism and chemotaxis, suggesting that these 2 processes are not linked.

  7. Improving arachidonic acid fermentation by Mortierella alpina through multistage temperature and aeration rate control in bioreactor. (United States)

    Gao, Min-Jie; Wang, Cheng; Zheng, Zhi-Yong; Zhu, Li; Zhan, Xiao-Bei; Lin, Chi-Chung


    Effective production of arachidonic acid (ARA) using Mortierella alpina was conducted in a 30-L airlift bioreactor. Varying the aeration rate and temperature significantly influenced cell morphology, cell growth, and ARA production, while the optimal aeration rate and temperature for cell growth and product formation were quite different. As a result, a two-stage aeration rate control strategy was constructed based on monitoring of cell morphology and ARA production under various aeration rate control levels (0.6-1.8 vvm). Using this strategy, ARA yield reached 4.7 g/L, an increase of 38.2% compared with the control (constant aeration rate control at 1.0 vvm). Dynamic temperature-control strategy was implemented based on the fermentation performance at various temperatures (13-28°C), with ARA level in total cellular lipid increased by 37.1% comparing to a constant-temperature control (25°C). On that basis, the combinatorial fermentation strategy of two-stage aeration rate control and dynamic temperature control was applied and ARA production achieved the highest level of 5.8 g/L.

  8. beta-oxidation modulates metabolic competition between eicosapentaenoic acid and arachidonic acid regulating prostaglandin E(2) synthesis in rat hepatocytes-Kupffer cells

    DEFF Research Database (Denmark)

    Du, Zhen-Yu; Ma, Tao; Winterthun, Synnøve;


    The ability of n-3 PUFA to competitively inhibit the use of arachidonic acid (AA) for membrane phospholipid synthesis and prostaglandin E(2) (PGE(2)) production has been well demonstrated in single cell models. In the present study, we investigated the metabolic competition between AA and eicosap......The ability of n-3 PUFA to competitively inhibit the use of arachidonic acid (AA) for membrane phospholipid synthesis and prostaglandin E(2) (PGE(2)) production has been well demonstrated in single cell models. In the present study, we investigated the metabolic competition between AA...

  9. Arachidonic acid incorporation and turnover is decreased in sympathetically denervated rat heart. (United States)

    Patrick, Casey B; McHowat, Jane; Rosenberger, Thad A; Rapoport, Stanley I; Murphy, Eric J


    Heart sympathetic denervation can accompany Parkinson's disease, but the effect of this denervation on cardiac lipid-mediated signaling is unknown. To address this issue, rats were sympathetically denervated with 6-hydroxydopamine (6-OHDA, 50 mg/kg ip) and infused with 170 muCi/kg of either [1-(14)C]palmitic acid ([1-(14)C]16:0) or [1-(14)C]arachidonic acid ([1-(14)C]20:4 n-6), and kinetic parameters were assessed using a steady-state radiotracer model. Heart norepinephrine and epinephrine levels were decreased 82 and 85%, respectively, in denervated rats, and this correlated with a 34% reduction in weight gain in treated rats. Fatty acid tracer uptake was not significantly different between groups for either tracer, although the dilution coefficient lambda was increased in [1-(14)C]20:4 n-6-infused rats, which indicates that less 20:4 n-6 was recycled in denervated rats. In [1-(14)C]16:0-infused rats, incorporation rate and turnover values of 16:0 in stable lipid compartments were unchanged, which is indicative of preservation of beta-oxidation. In [1-(14)C]20:4 n-6-infused rats, there were dramatic reductions in incorporation rate (60-84%) and turnover value (56-85%) in denervated rats that were dependent upon the lipid compartment. In addition, phospholipase A(2) activity was reduced 40% in treated rats, which is consistent with the reduction observed in 20:4 n-6 turnover. These results demonstrate marked reductions in 20:4 n-6 incorporation rate and turnover in sympathetic denervated rats and thereby suggest an effect on lipid-mediated signal transduction mediated by a reduction in phospholipase A(2) activity.

  10. Repurposing Resveratrol and Fluconazole To Modulate Human Cytochrome P450-Mediated Arachidonic Acid Metabolism. (United States)

    El-Sherbeni, Ahmed A; El-Kadi, Ayman O S


    Cytochrome P450 (P450) enzymes metabolize arachidonic acid (AA) to several biologically active epoxyeicosatrienoic acids (EETs) and hydroxyeicosatetraenoic acids (HETEs). Repurposing clinically-approved drugs could provide safe and readily available means to control EETs and HETEs levels in humans. Our aim was to determine how to significantly and selectively modulate P450-AA metabolism in humans by clinically-approved drugs. Liquid chromatography-mass spectrometry was used to determine the formation of 15 AA metabolites by human recombinant P450 enzymes, as well as human liver and kidney microsomes. CYP2C19 showed the highest EET-forming activity, while CYP1B1 and CYP2C8 showed the highest midchain HETE-forming activities. CYP1A1 and CYP4 showed the highest subterminal- and 20-HETE-forming activity, respectively. Resveratrol and fluconazole produced the most selective and significant modulation of hepatic P450-AA metabolism, comparable to investigational agents. Monte Carlo simulations showed that 90% of human population would experience a decrease by 6-22%, 16-39%, and 16-35% in 16-, 18-, and 20-HETE formation, respectively, after 2.5 g daily of resveratrol, and by 22-31% and 14-23% in 8,9- and 14,15-EET formation after 50 mg of fluconazole. In conclusion, clinically-approved drugs can provide selective and effective means to modulate P450-AA metabolism, comparable to investigational drugs. Resveratrol and fluconazole are good candidates to be repurposed as new P450-based treatments.

  11. Supplementation of DHA but not DHA with arachidonic acid during pregnancy and lactation influences general movement quality in 12-week-old term infants

    NARCIS (Netherlands)

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


    DHA and arachidonic acid (AA) are important for neurodevelopment. A traditional neonatal neurological examination and the evaluation of general movement quality are sensitive techniques for assessing neurodevelopment in young infants. Mildly abnormal general movement,,; at 3 months have been associa

  12. Effect of Arachidonic Acid on the Rate of Oxygen Consumption in Isolated Cardiomyocytes from Intact Rats and Animals with Ischemic or Diabetic Injury to the Heart. (United States)

    Egorova, M V; Kutsykova, T V; Afanas'ev, S A; Popov, S V


    We studied the rate of oxygen consumption by isolated cardiomyocytes from intact rats and animals with experimental myocardial infarction or streptozotocin-induced diabetes mellitus. The measurements were performed in standard incubation medium under various conditions of oxygenation and after addition of arachidonic acid (20 μmol/liter). Under normoxic conditions, arachidonic acid improves respiration of cardiomyocytes from intact animals, but reduces this parameter in cells isolated from animals with pathologies. The intensity of O2 consumption by cardiomyocytes from intact rats and animals with pathologies was shown to decrease during hypoxia. Addition of arachidonic acid aggravated inhibition of respiration for cardiomyocytes from intact rats and specimens with myocardial infarction, but had no effect in diabetes mellitus. The effect of arachidonic acid on oxygen consumption rate is probably mediated by a nonspecific mechanism realized at the mitochondrial level.

  13. Protective effects of arachidonic acid against palmitic acid-mediated lipotoxicity in HIT-T15 cells. (United States)

    Cho, Young Sik; Kim, Chi Hyun; Kim, Ki Young; Cheon, Hyae Gyeong


    Saturated fatty acids have been considered major contributing factors in type 2 diabetes, whereas unsaturated fatty acids have beneficial effects for preventing the development of diabetes. However, the effects of polyunsaturated fatty acids in pancreatic β cells have not been reported. Here, we examined the effects of arachidonic acid (AA) on palmitic acid (PA)-mediated lipotoxicity in clonal HIT-T15 pancreatic β cells. AA prevented the PA-induced lipotoxicity as indicated by cell viability, DNA fragmentation and mitochondrial membrane potential, whereas eicosatetraynoic acid (ETYA), a non-metabolizable AA, had little effect on PA-induced lipotoxicity. In parallel with its protective effects against PA-induced lipotoxicity, AA restored impaired insulin expression and secretion induced by PA. AA but not ETYA increased intracellular triglyceride (TG) in the presence of PA compared with PA alone, and xanthohumol, a diacylglycerol acyltransferase (DGAT) inhibitor, reversed AA-induced protection from PA. Taken together, our results suggest that AA protects against PA-induced lipotoxicity in clonal HIT-T15 pancreatic β cells, and the protective effects may be associated with TG accumulation, possibly through sequestration of lipotoxic PA into TG.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Ultraviolet B irradiation induces changes in the distribution and release of arachidonic acid, dihomo-gamma-linolenic acid, and eicosapentaenoic acid in human keratinocytes in culture

    Energy Technology Data Exchange (ETDEWEB)

    Punnonen, K.; Puustinen, T.; Jansen, C.T.


    There is increasing evidence that derivatives of 20-carbon polyunsaturated fatty acids, the eicosanoids, play an important role in the inflammatory responses of the human skin. To better understand the metabolic fate of fatty acids in the skin, the effect of ultraviolet B (UVB) irradiation (280-320 nm) on the distribution and release of /sup 14/C-labeled arachidonic acid, dihomo-gamma-linolenic acid, and eicosapentaenoic acid in human keratinocytes in culture was investigated. Ultraviolet B irradiation induced the release of all three /sup 14/C-labeled fatty acids from the phospholipids, especially from phosphatidylethanolamine, and this was accompanied by increased labeling of the nonphosphorus lipids. This finding suggests that UVB induces a significant liberation of eicosanoid precursor fatty acids from cellular phospholipids, but the liberated fatty acids are largely reincorporated into the nonphosphorus lipids. In conclusion, the present study suggests that not only arachidonic acid but also dihomo-gamma-linolenic acid, and eicosapentaenoic acid might be involved in the UVB irradiation-induced inflammatory reactions of human skin.

  16. Extracts from Tribulus species may modulate platelet adhesion by interfering with arachidonic acid metabolism. (United States)

    Olas, Beata; Hamed, Arafa I; Oleszek, Wieslaw; Stochmal, Anna


    The present work was designed to study the effects of crude extracts from Tribulus pterocarpus, T. pentandrus and T. parvispinus on selected biological functions of human blood platelets in vitro. Platelet suspensions were pre-incubated with extracts from aerial parts of T. pterocarpus, T. pentandrus and T. parvispinus, at the final concentrations of 0.5, 5 and 50 µg/ml. Then, for platelet activation thrombin, was used. The effects of crude extracts from T. pterocarpus, T. pentandrus and T. parvispinus on adhesion of blood platelets to collagen were determined by method according to Tuszynski and Murphy. Arachidonic acid metabolism was measured by the level of thiobarbituric acid reactive substances (TBARS). In these studies we also compared the action of tested crude plant extracts with the effects of the polyphenolic fraction isolated from aerial parts of T. pterocarpus, which has antiplatelet and antioxidative properties. The performed assays demonstrated that the tested crude extract from T. pterocarpus and the phenolic fraction from T. pterocarpus might influence the platelet functions in vitro. The inhibitory, concentration-dependent effects of this tested extract and its phenolic fraction on adhesion of resting platelets and thrombin - stimulated platelets to collagen was found. We also observed that the crude extract from T. pterocarpus, like the polyphenolic fraction from T. pterocarpus reduced TBARS production in blood platelets. In the comparative studies, the tested crude extract from T. pterocarpus was not found to be more effective antiplatelet factor, than the polyphenolic fraction from this plant. The results obtained suggest that T. pterocarpus may be a promising source of natural compounds, valuable in the prevention of the enhanced activity of blood platelets in numerous cardiovascular diseases.

  17. 2,3-Diarylxanthones as Potential Inhibitors of Arachidonic Acid Metabolic Pathways. (United States)

    Santos, Clementina M M; Ribeiro, Daniela; Silva, Artur M S; Fernandes, Eduarda


    In response to an inflammatory stimulus, arachidonic acid (AA), the main polyunsaturated fatty acid present in the phospholipid layer of cell membranes, is released and metabolized to a series of eicosanoids. These bioactive lipid mediators of inflammation arise physiologically through the action of the enzymes 5-lipoxygenase (5-LOX) and cyclooxygenases (constitutive COX-1 and inducible COX-2). It is believed that dual inhibition of 5-LOX and COXs may have a higher beneficial impact in the treatment of inflammatory disorders rather than the inhibition of each enzyme. With this demand for new dual-acting anti-inflammatory agents, a range of 2,3-diarylxanthones were tested through their ability to interact in the AA metabolism. In vitro anti-inflammatory activity was evaluated through the inhibition of 5-LOX-catalyzed leukotriene B4 (LTB4) formation in human neutrophils and inhibition of COX-1- and COX-2-catalyzed prostaglandin E2 (PGE2) formation in human whole blood. The results showed that some of the studied arylxanthones were able to prevent LTB4 production in human neutrophils, in a concentration-dependent manner. The xanthone with a 2-catechol was the most active one (IC50 ∼ 9 μM). The more effective arylxanthones in preventing COX-1-catalyzed PGE2 production presented IC50 values from 1 to 7 μM, exhibiting a structural feature with at least one non-substituted aryl group. All the studied arylxanthones were ineffective to prevent the formation of PGE2 catalyzed by COX-2, up to the maximum concentration of 100 μM. The ability of the tested 2,3-diarylxanthones to interact with both 5-LOX and COX-1 pathways constitutes an important step in the research of novel dual-acting anti-inflammatory drugs.

  18. Extract of a spice--omum (Trachyspermum ammi)-shows antiaggregatory effects and alters arachidonic acid metabolism in human platelets. (United States)

    Srivastava, K C


    An ethereal extract of omum (Trachyspermum ammi; Hindustani: ajwan)--a frequently consumed spice--was found to inhibit platelet aggregation induced by arachidonic acid (AA), epinephrine and collagen; in this respect it was most effective against AA-induced aggregation. Inhibition of aggregation by omum could be explained by its effect on platelet thromboxane production as suggested by the following experimental observation. (i) Omum reduced TxB2 formation in intact platelet preparations from added arachidonate, and (ii) it reduced the formation of TxB2 from AA-labelled platelets after stimulation with Ca2+-ionophore A23187 by a direct action on cyclooxygenase as it did not affect the release of AA from labelled platelets. An increased formation of lipoxygenase-derived products from exogenous AA in omum-treated platelets was apparently due to redirection of AA from cyclooxygenase to the lipoxygenase pathway.

  19. Immunopathogenesis of HIV infection in cocaine users: role of arachidonic acid. (United States)

    Samikkannu, Thangavel; Rao, Kurapati V K; Ding, Hong; Agudelo, Marisela; Raymond, Andrea D; Yoo, Changwon; Nair, Madhavan P N


    Arachidonic acid (AA) is known to be increased in HIV infected patients and illicit drug users are linked with severity of viral replication, disease progression, and impaired immune functions. Studies have shown that cocaine accelerates HIV infection and disease progression mediated by immune cells. Dendritic cells (DC) are the first line of antigen presentation and defense against immune dysfunction. However, the role of cocaine use in HIV associated acceleration of AA secretion and its metabolites on immature dendritic cells (IDC) has not been elucidated yet. The aim of this study is to elucidate the mechanism of AA metabolites cyclooxygenase-2 (COX-2), prostaglandin E2 synthetase (PGE2), thromboxane A2 receptor (TBXA2R), cyclopentenone prostaglandins (CyPG), such as 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2), 14-3-3 ζ/δ and 5-lipoxygenase (5-LOX) mediated induction of IDC immune dysfunctions in cocaine using HIV positive patients. The plasma levels of AA, PGE2, 15d-PGJ2, 14-3-3 ζ/δ and IDC intracellular COX-2 and 5-LOX expression were assessed in cocaine users, HIV positive patients, HIV positive cocaine users and normal subjects. Results showed that plasma concentration levels of AA, PGE2 and COX-2, TBXA2R and 5-LOX in IDCs of HIV positive cocaine users were significantly higher whereas 15d-PGJ2 and 14-3-3 ζ/δ were significantly reduced compared to either HIV positive subjects or cocaine users alone. This report demonstrates that AA metabolites are capable of mediating the accelerative effects of cocaine on HIV infection and disease progression.

  20. Immunopathogenesis of HIV infection in cocaine users: role of arachidonic acid.

    Directory of Open Access Journals (Sweden)

    Thangavel Samikkannu

    Full Text Available Arachidonic acid (AA is known to be increased in HIV infected patients and illicit drug users are linked with severity of viral replication, disease progression, and impaired immune functions. Studies have shown that cocaine accelerates HIV infection and disease progression mediated by immune cells. Dendritic cells (DC are the first line of antigen presentation and defense against immune dysfunction. However, the role of cocaine use in HIV associated acceleration of AA secretion and its metabolites on immature dendritic cells (IDC has not been elucidated yet. The aim of this study is to elucidate the mechanism of AA metabolites cyclooxygenase-2 (COX-2, prostaglandin E2 synthetase (PGE2, thromboxane A2 receptor (TBXA2R, cyclopentenone prostaglandins (CyPG, such as 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2, 14-3-3 ζ/δ and 5-lipoxygenase (5-LOX mediated induction of IDC immune dysfunctions in cocaine using HIV positive patients. The plasma levels of AA, PGE2, 15d-PGJ2, 14-3-3 ζ/δ and IDC intracellular COX-2 and 5-LOX expression were assessed in cocaine users, HIV positive patients, HIV positive cocaine users and normal subjects. Results showed that plasma concentration levels of AA, PGE2 and COX-2, TBXA2R and 5-LOX in IDCs of HIV positive cocaine users were significantly higher whereas 15d-PGJ2 and 14-3-3 ζ/δ were significantly reduced compared to either HIV positive subjects or cocaine users alone. This report demonstrates that AA metabolites are capable of mediating the accelerative effects of cocaine on HIV infection and disease progression.

  1. Regulation of rat intrapulmonary arterial tone by arachidonic acid and prostaglandin E2 during hypoxia.

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    Gaoliang Yan

    Full Text Available AIMS: Arachidonic acid (AA and its metabolites, prostaglandins (PG are known to be involved in regulation of vascular homeostasis including vascular tone and vessel wall tension, but their potential role in Hypoxic pulmonary vasoconstriction (HPV remains unclear. In this study, we examined the effects of AA and PGE2 on the hypoxic response in isolated rat intrapulmonary arteries (IPAs. METHODS AND RESULTS: We carried out the investigation on IPAs by vessel tension measurement. Isotetrandrine (20 µM significantly inhibited phase I, phase IIb and phase IIc of hypoxic vasoconstriction. Both indomethacin (100 µM and NS398 attenuated KPSS-induced vessel contraction and phase I, phase IIb and phase IIc of HPV, implying that COX-2 plays a primary role in the hypoxic response of rat IPAs. PGE2 alone caused a significant vasoconstriction in isolated rat IPAs. This constriction is mediated by EP4. Blockage of EP4 by L-161982 (1 µM significantly inhibited phase I, phase IIb and phase IIc of hypoxic vasoconstriction. However, AH6809 (3 µM, an antagonist of EP1, EP2, EP3 and DP1 receptors, exerted no effect on KPSS or hypoxia induced vessel contraction. Increase of cellular cAMP by forskolin could significantly reduce KPSS-induced vessel contraction and abolish phase I, phase II b and phase II c of HPV. CONCLUSION: Our results demonstrated a vasoconstrictive effect of PGE2 on rat IPAs and this effect is via activation of EP4. Furthermore, our results suggest that intracellular cAMP plays dual roles in regulation of vascular tone, depending on the spatial distribution of cAMP and its coupling with EP receptor and Ca(2+ channels.

  2. The 5-lipoxygenase inhibitor, zileuton, suppresses prostaglandin biosynthesis by inhibition of arachidonic acid release in macrophages (United States)

    Rossi, A; Pergola, C; Koeberle, A; Hoffmann, M; Dehm, F; Bramanti, P; Cuzzocrea, S; Werz, O; Sautebin, L


    BACKGROUND AND PURPOSE Zileuton is the only 5-lipoxygenase (5-LOX) inhibitor marketed as a treatment for asthma, and is often utilized as a selective tool to evaluate the role of 5-LOX and leukotrienes. The aim of this study was to investigate the effect of zileuton on prostaglandin (PG) production in vitro and in vivo. EXPERIMENTAL APPROACH Peritoneal macrophages activated with lipopolysaccharide (LPS)/interferon γ (LPS/IFNγ), J774 macrophages and human whole blood stimulated with LPS were used as in vitro models and rat carrageenan-induced pleurisy as an in vivo model. KEY RESULTS Zileuton suppressed PG biosynthesis by interference with arachidonic acid (AA) release in macrophages. We found that zileuton significantly reduced PGE2 and 6-keto prostaglandin F1α (PGF1α) levels in activated mouse peritoneal macrophages and in J774 macrophages. This effect was not related to 5-LOX inhibition, because it was also observed in macrophages from 5-LOX knockout mice. Notably, zileuton inhibited PGE2 production in LPS-stimulated human whole blood and suppressed PGE2 and 6-keto PGF1α pleural levels in rat carrageenan-induced pleurisy. Interestingly, zileuton failed to inhibit the activity of microsomal PGE2 synthase1 and of cyclooxygenase (COX)-2 and did not affect COX-2 expression. However, zileuton significantly decreased AA release in macrophages accompanied by inhibition of phospholipase A2 translocation to cellular membranes. CONCLUSIONS AND IMPLICATION Zileuton inhibited PG production by interfering at the level of AA release. Its mechanism of action, as well as its use as a pharmacological tool, in experimental models of inflammation should be reassessed. PMID:20880396

  3. Effect of in vivo coal dust exposure on arachidonic acid metabolism in the rat alveolar macrophage

    Energy Technology Data Exchange (ETDEWEB)

    Kuhn, D.C.; Stanley, C.F.; El-Ayouby, N.; Demers, L.M. (Pennsylvania State Univ., Hershey, PA (USA). M.S. Hershey Medical Center, Dept. of Pathology)


    Oxygenated metabolites of arachidonic acid (AA) are produced by the alveolar macrophage (AM) and have been shown to mediate inflammatory reactions. We therefore assessed the production of eicosanoids by AM harvested from the lungs of rats exposed to a bituminous coal dust for 2 wk in an inhalation chamber in order to determine if AA metabolism was altered in a manner that may promote an inflammatory response in the lung. Exposure to coal dust resulted in a 66% increase in the number of AM harvested, an increase in thromboxane A{sub 2}(TxA{sub 2}) and leukotriene B{sub 4} (LTB{sub 4}) production to 222% and 181% of control values, respectively, and a decrease in prostaglandin E{sub 2} (PGE{sub 2}) production to 62% of control values. In AM harvested from rats allowed to breathe clean air for 2 wk following coal dust exposure, PGE{sub 2} production returned to control levels but TxA{sub 2} and LTB{sub 4} production remained elevated. The TxA{sub 2} synthesis inhibitor UK 38,485 reduced TxA{sub 2} production in dust-exposed AM both immediately and 2 wk following exposure. Thus, exposure of rats to coal dust significantly alters the metabolism of AA in AM, with potentially important aspects of AA metabolism remaining altered even after a 2-wk recovery period. Based on the established role of eicosanoids in inflammatory and fibrotic processes, these results suggest that the alteration of AM eicosanoid production as a result of the inhalation of coal mine dust may be an important factor in the pathophysiology of coal workers' pneumoconiosis. 26 refs., 4 figs.

  4. Year-round high arachidonic acid levels in herbivorous rabbit fish Siganus fuscescens tissues. (United States)

    Osako, Kazufumi; Saito, Hiroaki; Kuwahara, Koichi; Okamoto, Akira


    To identify a stable resource of 20:4 n-6 (arachidonic acid, AA) in marine fish tissues, the lipid profiles of Siganus fuscescens organs (muscle, liver, and other viscera) and stomach contents were examined throughout the year. Crude total lipid (TL) contents in respective organs showed seasonal variations and were high in winter and low in summer. The main FA in TL were 16:0, 18:0, 16:1n-7, 18:1n-9, AA, and 22:6n-3 (DHA). These FA were those generally observed in marine fish lipids, except for comparatively high levels of AA. In TL of muscle and liver, AA showed relatively high values during the period from late May to August (muscle, 4.6-13.1%; liver, 4.5-9.1%), compared with other seasons (muscle, 4.3-9.5%; liver, 3.6-8.4%). The AA levels in TL of other viscera and stomach contents fluctuated (other viscera, 2.0-10.7%; stomach contents, 7.6-26.7%). Regardless of the fishing season, each organ contained a higher level of AA in polar lipids (PL) than in neutral lipids. It was concluded that the fish contain comparatively high levels of AA in their TL throughout the year, and they accumulate AA characteristically in their tissue PL, probably from dietary food sources. Moreover, it was suggested that S. fuscescens has potential utility as a natural marine source of nutritional lipids, because the fish contain comparatively high levels of DHA and AA.

  5. Allometric scaling of dietary linoleic acid on changes in tissue arachidonic acid using human equivalent diets in mice

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    Whelan Jay


    Full Text Available Abstract Background It is hypothesized that dietary linoleic acid (LA promotes chronic and acute diseases in humans by enriching tissues with arachidonic acid (AA, its downstream metabolite, and dietary studies with rodents have been useful for validation. However, levels of LA in research diets of rodents, as published in the literature, are notoriously erratic making interspecies comparisons unreliable. Therefore, the ability to extrapolate the biological effects of dietary LA from experimental rodents to humans necessitates an allometric scaling model that is rooted within a human equivalent context. Methods To determine the physiological response of dietary LA on tissue AA, a mathematical model for extrapolating nutrients based on energy was used, as opposed to differences in body weight. C57BL/6J mice were divided into 9 groups fed a background diet equivalent to that of the US diet (% energy with supplemental doses of LA or AA. Changes in the phospholipid fatty acid compositions were monitored in plasma and erythrocytes and compared to data from humans supplemented with equivalent doses of LA or AA. Results Increasing dietary LA had little effect on tissue AA, while supplementing diets with AA significantly increased tissue AA levels, importantly recapitulating results from human trials. Conclusions Thus, interspecies comparisons for dietary LA between rodents and humans can be achieved when rodents are provided human equivalent doses based on differences in metabolic activity as defined by energy consumption.

  6. Pathways of arachidonic acid peroxyl radical reactions and product formation with guanine radicals. (United States)

    Crean, Conor; Geacintov, Nicholas E; Shafirovich, Vladimir


    Peroxyl radicals were derived from the one-electron oxidation of polyunsaturated fatty acids by sulfate radicals that were generated by the photodissociation of peroxodisulfate anions in air-equilibrated aqueous solutions. Reactions of these peroxyl and neutral guanine radicals, also generated by oxidation with sulfate radicals, were investigated by laser kinetic spectroscopy, and the guanine oxidation products were identified by HPLC and mass spectrometry methods. Sulfate radicals rapidly oxidize arachidonic (ArAc), linoleic (LnAc), and palmitoleic (PmAc) acids with similar rate constants, (2-4) x 10 (9) M (-1) s (-1). The C-centered radicals derived from the oxidation of ArAc and LnAc include nonconjugated Rn(.) ( approximately 80%) and conjugated bis-allylic Rba(.) ( approximately 20%) radicals. The latter were detectable in the absence of oxygen by their prominent, narrow absorption band at 280 nm. The Rn(.) radicals of ArAc (containing three bis-allylic sites) transform to the Rba(.) radicals via an intramolecular H-atom abstraction [rate constant (7.5 +/- 0.7) x 10 (4) s (-1)]. In contrast, the Rn(.) radicals of LnAc that contain only one bis-allylic site do not transform intramolecularly to the Rba(.) radicals. In the case of PmAc, which contains only one double bond, the Rba(.) radicals are not observed. The Rn(.) radicals of PmAc rapidly combine with oxygen with a rate constant of (3.8 +/- 0.4) x 10(9) M(-1) s(-1). The Rba(.) radicals of ArAc are less reactive and react with oxygen with a rate constant of (2.2 +/- 0.2) x 10 (8) M (-1) s (-1). The ArAc peroxyl radicals formed spontaneously eliminate superoxide radical anions [rate constant = (3.4 +/- 0.3) x 10 (4) M (-1) s (-1)]. The stable oxidative lesions derived from the 2',3',5'-tri- O-acetylguanosine or 2',3',5'-tri- O-acetyl-8-oxo-7,8-dihydroguanosine radicals and their subsequent reactions with ArAc peroxyl radicals were also investigated. The major products found were the 2,5-diamino-4 H

  7. In vitro ozone exposure increases release of arachidonic acid products from a human bronchial epithelial cell line

    Energy Technology Data Exchange (ETDEWEB)

    McKinnon, K.P.; Madden, M.C.; Noah, T.L.; Devlin, R.B. (TRC Environmental Corporation, Chapel Hill, NC (United States))


    Eicosanoids released after ozone exposure of a human bronchial epithelial cell line, BEAS-S6, were analyzed by high-pressure liquid chromatography (HPLC) of supernatants from exposed cells prelabeled with [3H]arachidonic acid. BEAS cells released thromboxane B2 (TxB2), prostaglandin E2 (PGE2), leukotriene C4 (LTC4), LTD4, LTE4, and 12-hydroxyheptadecatrienoic acid (HHT) after exposure to ozone at concentrations of 0.1, 0.25, 0.5, and 1.0 ppm. The eicosanoids were identified by coelution with authentic standards. The largest product from ozone-exposed BEAS cells was the most polar peak, designated Peak 1. Release of cyclooxygenase products such as TxB2, PGE2, and HHT was inhibited by acetylsalicylic acid. Peaks that migrated with authentic standards for LTB4, LTC4, and LTD4 were inhibited by the lipoxygenase inhibitor nordihydroguaiaretic acid. The leukotrienes LTB4 and LTC4/D4 could also be detected by immunoassay of concentrated peak fractions. Thus BEAS cells released eicosanoids from cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism following exposure to ozone. Airway epithelial cells may be an important source of eicosanoids following ozone stimulation in humans.

  8. Arachidonic Acid and Cerebral Ischemia Risk: A Systematic Review of Observational Studies

    Directory of Open Access Journals (Sweden)

    Mai Sakai


    Full Text Available Background: Arachidonic acid (ARA is a precursor of various lipid mediators. ARA metabolites such as thromboxane A2 cause platelet aggregation and vasoconstriction, thus may lead to atherosclerotic disease. It is unclear whether dietary ARA influences the ARA-derived lipid mediator balance and the risk for atherosclerotic diseases, such as cerebral ischemia. Considering the function of ARA in atherosclerosis, it is reasonable to focus on the atherothrombotic type of cerebral ischemia risk. However, no systematic reviews or meta-analyses have been conducted to evaluate the effect of habitual ARA exposure on cerebral ischemia risk. We aimed to systematically evaluate observational studies available on the relationship between ARA exposure and the atherothrombotic type of cerebral ischemia risk in free-living populations. Summary: The PubMed database was searched for articles registered up to June 24, 2014. We designed a PubMed search formula as follows: key words for humans AND brain ischemia AND study designs AND ARA exposure. Thirty-three articles were reviewed against predefined criteria. There were 695 bibliographies assessed from the articles that included both ARA and cerebral ischemia descriptions. Finally, we identified 11 eligible articles and categorized them according to their reporting and methodological quality. We used the Strengthening the Reporting of Observational Studies in Epidemiology Statement (STROBE checklist to score the reporting quality. The methodological quality was qualitatively assessed based on the following aspects: subject selection, ARA exposure assessment, outcome diagnosis, methods for controlling confounders, and statistical analysis. We did not conduct a meta-analysis due to the heterogeneity among the studies. All eligible studies measured blood ARA levels as an indicator of exposure. Our literature search did not identify any articles that evaluated dietary ARA intake and tissue ARA as assessments of

  9. The role of arachidonic acid metabolism in virus-induced alveolar macrophage dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Laegreid, W.W.


    Alveolar macrophages (AM) recovered from virus-infected lungs have decreased phagocytic, respiratory burst and bactericidal activities. The studies described below investigated the role of eicosanoids in virus induced AM bactericidal dysfunction. The spectrum of eicosanoid metabolites which bovine AM are capable of producing was determined. Cultured AM were exposed to {sup 3}H-arachidonate for 1 hour, stimulated for 4 hours with A23187, phorbol myristate acetate or zymosan and the supernatants extracted and analyzed by HPLC. All stimuli tested caused the release of these cyclooxygenase metabolites: thromboxane B{sub 2}, PGF{sub 2}, PGE{sub 2}, PGD{sub 2} and HHT. The effect of this enhanced release of arachidonate metabolites on the ability of AM to kill bacteria was evaluated. Preincubation with cyclooxygenase inhibitors or dual cyclooxygenase and lipoxygenase inhibitors resulted in partial reversal of the virus-induced bactericidal deficit in PI3 infected AM.

  10. Dietary fatty acids and the stress response of fish : arachidonic acid in seabream and tilapia

    NARCIS (Netherlands)

    Anholt, Rogier Daniël van


    A key factor in the production of fish in commercial aquaculture is the optimization of the artificial diets, not only to achieve optimal growth, but also to maximize fish health. Evidence is accumulating that dietary lipids, particularly the fatty acid composition, can have a direct effect on the f

  11. Effect of extra virgin olive oil components on the arachidonic acid cascade, colorectal cancer and colon cancer cell proliferation

    Directory of Open Access Journals (Sweden)

    C. E. Storniolo


    Full Text Available The mediterranean diet (MD reduced the risk of colorectal cancer (CRC, and olive oil, the primary source of fat in the MD, has also been found to have a protective effect. However, animals fed with oleic acid present a high number of intestinal tumours, suggesting that oleic acid and olive oil consumption can exert different effects on CRC. Considering that extra virgin olive oil (EVOO is a complex mix of fatty acids and minor compounds such as polyphenols, hydrocarbons, phytosterols and triterpenes; and that these compounds have antioxidant activity and consequently they can modulate the arachidonic acid (AA cascade and eicosanoid synthesis. This review analyzes the state of the art of olive oil components on the AA cascade and cellular mechanism involved in CRC such as intestinal epithelial cell growth/apoptosis, to understand the fact that the consumption of seed oils with high oleic content or EVOO will probably have different effects on CRC development.

  12. Decreases in Phospholipids Containing Adrenic and Arachidonic Acids Occur in the Human Hippocampus over the Adult Lifespan. (United States)

    Hancock, Sarah E; Friedrich, Michael G; Mitchell, Todd W; Truscott, Roger J W; Else, Paul L


    One of the biggest risk factors for developing Alzheimer's disease is advanced age. Despite several studies examining changes to phospholipids in the hippocampus during the pathogenesis of Alzheimer's disease, little is known regarding changes to phospholipids in this region during normal adult aging. This study examined the phospholipid composition of the mitochondrial and microsomal membranes of the human hippocampus from post-mortem tissue of neurologically normal subjects aged between 18 and 104 years. Many of the age-related changes found were in low-to-moderately abundant phospholipids in both membrane fractions, with decreases with age being seen in many phospholipids containing either adrenic or arachidonic acid. The most abundant phospholipid of this type was phosphatidylethanolamine 18:0_22:4, which decreased in both the mitochondrial and microsomal membranes by approximately 20% from ages 20 to 100. Subsequent decreases with age were seen in total adrenic and arachidonic acid in the phospholipids of both membrane fractions, but not in either fatty acid specifically within the phosphatidylethanolamine class. Increases with age were seen in the hippocampus for mitochondrial phosphatidylserine 18:0_22:6. This is the first report of changes to molecular phospholipids of the human hippocampus over the adult lifespan, with this study also providing a comprehensive profile of the phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine phospholipids of the human hippocampus.

  13. An Optimized High Throughput Clean-Up Method Using Mixed-Mode SPE Plate for the Analysis of Free Arachidonic Acid in Plasma by LC-MS/MS


    Wan Wang; Suzi Qin; Linsen Li; Xiaohua Chen; Qunjie Wang; Junfu Wei


    A high throughput sample preparation method was developed utilizing mixed-mode solid phase extraction (SPE) in 96-well plate format for the determination of free arachidonic acid in plasma by LC-MS/MS. Plasma was mixed with 3% aqueous ammonia and loaded into each well of 96-well plate. After washing with water and methanol sequentially, 3% of formic acid in acetonitrile was used to elute arachidonic acid. The collected fraction was injected onto a reversed phase column at 30°C with mobile pha...

  14. Impact of arachidonic acid enrichment of live rotifer prey on bacterial communities in rotifer and larval fish cultures. (United States)

    Seychelles, Laurent H; Doiron, Kim; Audet, Céline; Tremblay, Réjean; Pernet, Fabrice; Lemarchand, Karine


    Rotifers (Brachionus plicatilis), commonly used at first feeding in commercial fish hatcheries, carry a large bacteria load. Because they are relatively poor in essential fatty acids, it is common practice to enrich them with fatty acids, including arachidonic acid (AA). This study aims to determine whether prey enrichment with AA may act as a prebiotic and modify the microbial community composition either in AA-enriched rotifer cultures or in larval-rearing water using winter flounder (Pseudopleuronectes americanus) as a larval fish model. AA enrichment modified the bacterial community composition in both the rotifer culture tanks and the larval-rearing tanks. We observed an increase in the number of cultivable bacteria on TCBS (thiosulfate-citrate-bile salts-sucrose) agar, used as a proxy for the abundance of Vibrio sp. The results suggest that AA may also play an indirect role in larval health.

  15. Lyso(bis)phosphatidic acid: a preferred donor of arachidonic acid for macrophage-synthesis of eicosanoids

    Energy Technology Data Exchange (ETDEWEB)

    Cochran, F.; Roddick, V.; Connor, J.; Waite, M.


    In order to dissect mechanisms of arachidonic acid (20:4) metabolism, two cell populations were investigated, resident (AM) and Bacillus Calmette-Guerin-activated (BCG-AM) rabbit alveolar macrophages. After purified AM were labeled overnight with (/sup 3/H)20:4, radioactivity was localized primarily within lyso(bis)phosphatidic acid (L(bis)PA) (13.1%), phosphatidylethanolamine (PE) (22.8%) and phosphatidylcholine (PC) (26.7%), with lesser amounts recovered in phosphatidyl-serine (PS) plus phosphatidylinositol (PI) (9.2%). By contrast, analysis of the phospholipid classes from prelabeled BCG-AM revealed that the mass of L(bis)PA as well as its (/sup 3/H)20:4 content was profoundly decreased while other BCG-AM phospholipids remained unchanged. When (/sup 3/H)20:4-labeled AM were stimulated with 1 12-0-tetradecanoyl-phorbol-13-acetate (TPA), a loss of (/sup 3/H)20:4 was observed from L(bis)PA, PE, PC, and PS/PI with a corresponding increase in eicosanoid synthesis. BCG-AM exposed to either TPA or 3.8 Ca/sup +2/ ionophore A23187 liberated (/sup 3/H)20:4 solely from Pe and PC. BCG-AM, which exhibited depressed eicosanoid formation, consistently failed to deacylate (/sup 3/H)20:4 from L(bis)PA or PI. Their evidence suggests that the diminution of eicosanoid synthesis by BCG-AM may be due to the reduction of 20:4 contained within specific phospholipid pools, namely L(bis)PA.

  16. Combining eicosapentaenoic acid, decosahexaenoic acid and arachidonic acid, using a fully crossed design, affect gene expression and eicosanoid secretion in salmon head kidney cells in vitro. (United States)

    Holen, Elisabeth; He, Juyun; Espe, Marit; Chen, Liqiou; Araujo, Pedro


    Future feed for farmed fish are based on untraditional feed ingredients, which will change nutrient profiles compared to traditional feed based on marine ingredients. To understand the impact of oils from different sources on fish health, n-6 and n-3 polyunsaturated fatty acids (PUFAs) were added to salmon head kidney cells, in a fully crossed design, to monitor their individual and combined effects on gene expression. Exposing salmon head kidney cells to single fatty acids, arachidonic acid (AA) or decosahexaenoic acid (DHA), resulted in down-regulation of cell signaling pathway genes and specific fatty acid metabolism genes as well as reduced prostaglandin E2 (PGE2) secretion. Eicosapentaenoic acid (EPA) had no impact on gene transcription in this study, but reduced the cell secretion of PGE2. The combined effect of AA + EPA resulted in up-regulation of eicosanoid pathway genes and the pro-inflammatory cytokine, tumor necrosis factor alpha (TNF-α), Bclx (an inducer of apoptosis) and fatty acid translocase (CD36) as well as increased cell secretion of PGE2 into the media. Adding single fatty acids to salmon head kidney cells decreased inflammation markers in this model. The combination AA + EPA acted differently than the rest of the fatty acid combinations by increasing the inflammation markers in these cells. The concentration of fatty acid used in this experiment did not induce any lipid peroxidation responses.

  17. Decreased arachidonic acid content and metabolism in tissues of NZB/W F1 females fed a diet containing 0. 45% dehydroisoandrosterone (DHA)

    Energy Technology Data Exchange (ETDEWEB)

    Matsunaga, A.; Cottam, G.L.


    A diet containing 0.45% DHA fed to NZB/W mice, a model of systemic lupus erythematosus, delays the time of onset, improves survival and decreases the formation of antibodies to ds-DNA. Essential fatty acid-deficient diets or inclusion of eicosapentaenoic acid have similar beneficial effects and led them to investigate arachidonic acid metabolism in response to feeding DHA. The arachidonic acid content of plasma cholesteryl ester decreased from 37.4 +/- 2.2 to 28.2 +/- 1.3 mg%. In total liver phospholipid the value decreased from 18.1 +/- 0.52 to 13.7 +/- 1.3 mg%, in total kidney phospholipid the value decreased from 24.10 +/- 0.87 to 20.7 +/- 0.32 mg% and in resident peritoneal macrophages the value decreased from 15.4 +/- 4.6 to 3.6 +/- 1.4 mg%. The metabolism of exogenous (1-/sup 14/C)arachidonic acid by resident peritoneal macrophages in response to Zymosan stimulation for 2 hr was examined by extraction of metabolites and separation by HPLC. Cells isolated from DHA-fed animals produced less PGE2 than controls, yet similar amounts of 6-keto PGF1..cap alpha.. were produced. Arachidonic acid metabolites have significant effects on the immune system and may be a mechanism involved in the benefits obtained by inclusion of DHA in the diet.

  18. Heating of vegetable oils influences the activity of enzymes participating in arachidonic acid formation in Wistar rats. (United States)

    Stawarska, Agnieszka; Białek, Agnieszka; Tokarz, Andrzej


    Dietary intake of lipids and their fatty acids profile influence many aspects of health. Thermal processing changes the properties of edible oils and can also modify their metabolism, for example, eicosanoids formation. The aim of our study was to verify whether the activity of desaturases can be modified by lipids intake, especially by the fatty acids content. The experimental diets contained rapeseed oil, sunflower oil, and olive oil, both unheated and heated (for 10 minutes at 200 °C each time before administration), and influenced the fatty acids composition in serum and the activity of enzymes participating in arachidonic acid (AA) formation. The activity of desaturases was determined by measuring the amounts of AA formed in vitro derived from linoleic acid as determined in liver microsomes of Wistar rats. In addition, the indices of ∆(6)-desaturase (D6D) and ∆(5)-desaturase (D5D) have been determined. To realize this aim, the method of high-performance liquid chromatography has been used with ultraviolet-visible spectrophotometry detection. Diet supplementation with the oils rich in polyunsaturated fatty acids affects the fatty acids profile in blood serum and the activity of D6D and ∆(5)-desaturase in rat liver microsomes, the above activities being dependent on the kind of oil applied. Diet supplementation with heated oils has been found to increase the amount of AA produced in hepatic microsomes; and in the case of rapeseed oil and sunflower oil, it has also increased D6D activity.

  19. Biochemical and pharmacological effects of dipyrone and its metabolites in model systems related to arachidonic acid cascade. (United States)

    Weithmann, K U; Alpermann, H G


    The metabolites of dipyrone (metamizol, Novalgin) were compared with appropriate standard drugs for their influences on the pathways of the arachidonic acid metabolism. The drugs in this study had no significant effects on the lipoxygenase pathway in human neutrophils in vitro. The dipyrone metabolites 4-methylaminoantipyrine (MAAP) and 4-aminoantipyrine (AAP) inhibited prostaglandin synthesis in the 10(-3) to 10(-4) mol/l range thus being comparable to acetylsalicylic acid (ASA), whereas the two additional metabolites 4-acetylaminoantipyrine (AAAP) and 4-formylaminoantipyrine (FAAP) were practically inactive. This result is in accordance with the effects of the metabolites on the formation of oedema in the arthritis rat model, and supports published data showing that MAAP and AAP are the metabolites responsible for the clinical effects of dipyrone. Further systems in our study depending at least partially on the prostaglandin pathway were the release of antiaggregatory activity from rat aortae in vitro and the aggregation of human platelets induced by arachidonic acid in vitro. MAAP exhibits antiaggregatory activity (IC50 5 x 10(-6) mol/l), whereas the inhibitory effect on the vascular antiaggregatory release is much weaker. Compared to normals platelet aggregability ex vivo is enhanced in arthritic rats, but could significantly be lowered again by treatment of the rats with MAAP. A further system studied was the release of 6-keto-PGF1 alpha from rat mucosa in vitro and ex vivo. In vitro there is inhibition to be found with MAAP as well as with ASA. Ex vivo, however, dipyrone or MAAP slightly stimulates mucosal 6-keto-PGF1 alpha rather than inhibiting it, whereas ASA exerts inhibition, as expected.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Targeting arachidonic acid pathway to prevent programmed hypertension in maternal fructose-fed male adult rat offspring. (United States)

    Tain, You-Lin; Lee, Wei-Chia; Wu, Kay L H; Leu, Steve; Chan, Julie Y H


    Hypertension can be programmed in response to nutritional insults in early life. Maternal high-fructose (HF) intake induced programmed hypertension in adult male offspring, which is associated with renal programming and arachidonic acid metabolism pathway. We examined whether early treatment with a soluble epoxide hydrolase (SEH) inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) or 15-Deoxy-Δ(12,14)-prostagandin J2 (15dPGJ2) can prevent HF-induced programmed hypertension. Pregnant Sprague Dawley rats received regular chow or chow supplemented with fructose (60% diet by weight) during the whole period of pregnancy and lactation. Four groups of male offspring were studied: control, HF, HF+AUDA and HF+15dPGJ2. In HF+AUDA group, mother rats received AUDA 25 mg/L in drinking water during lactation. In the HF+15dPGJ2 group, male offspring received 15dPGJ2 1.5 mg/kg body weight by subcutaneous injection once daily for 1 week after birth. Rats were sacrificed at 12 weeks of age. Maternal HF-induced programmed hypertension is associated with increased renal protein level of SEH and oxidative stress, which early AUDA therapy prevents. Comparison of AUDA and 15dPGJ2 treatments demonstrated that AUDA was more effective in preventing HF-induced programmed hypertension. AUDA therapy increases angiotensin converting enzyme-2 (ACE2) protein levels and PGE2 levels in adult offspring kidney exposed to maternal HF. 15dPGJ2 therapy increases plasma asymmetric dimethylarginine (ADMA) levels and decreases L-arginine-to-ADMA ratio. Better understanding of the impact of arachidonic acid pathway, especially inhibition of SEH, on renal programming may aid in developing reprogramming strategy to prevent programmed hypertension in children exposed to antenatal HF intake.

  1. Synergism between thapsigargin and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate on the release of [C]arachidonic acid and histamine from rat peritoneal mast cells

    DEFF Research Database (Denmark)

    Jacobsen, S.; Hansen, Harald S.; Jensen, B.


    Thapsigargin is a potent skin irritating sesquiterpene lactone isolated from the roots of Thapsia garganica L. (Apiaceae). In rat peritoneal mast cells thapsigargin induced a calcium-dependent non-cytotoxic [C]arachidonic acid and histamine release. A minor amount of the released [C...

  2. Evaluation of a subchronic (13-week) oral toxicity study, preceded by an in utero exposure phase, with arachidonic acid oil derived from Mortierella alpina in rats

    NARCIS (Netherlands)

    Hempenius, R.A.; Lina, B.A.R.; Haggitt, R.C.


    Arachidonic acid oil (ARA-oil) derived from the fungus Mortierella alpina for use in infant nutrition was tested in a subchronic (13-week) oral toxicity study in rats, preceded by an in utero exposure phase. The ARA-oil was administered as admixture to the rodent diet at dose levels of 3000 ppm, 15,

  3. The relation between the omega-3 index and arachidonic acid is bell shaped : Synergistic at low EPA plus DHA status and antagonistic at high EPA plus DHA status

    NARCIS (Netherlands)

    Luxwolda, Martine F.; Kuipers, Remko S.; Smit, Ella N.; Velzing-Aarts, Francien V.; Dijck-Brouwer, D. A. Janneke; Muskiet, Frits A. J.


    Introduction: The relation between docosahexaenoic (DHA) and eicosapentaenoic (EPA) vs. arachidonic acid (AA) seems characterized by both synergism and antagonism. Materials and methods: Investigate the relation between EPA + DHA and AA in populations with a wide range of EPA + DHA status and across

  4. 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

  5. Stimulation of arachidonic acid metabolism in primary cultures of osteoblast-like cells by hormones and drugs

    Energy Technology Data Exchange (ETDEWEB)

    Feyen, J.H.; van der Wilt, G.; Moonen, P.; Di Bon, A.; Nijweide, P.J.


    The effects of parathyroid hormone (PTH), dihydroxycholecalciferol (1,25-(OH)2 D3), thrombin, epidermal growth factor (EGF) and 12-o-tetradecanoylphorbol-13-acetate (PMA) on the biosynthesis and release of arachidonic acid metabolites were studied in primary cultures of osteoblast-like cells isolated from 18-day-old chick embryo calvaria. Cells were labelled with (/sup 14/C)-arachidonic acid for 30 h. The radioactive eicosanoids were extracted from the cell culture media after a further 30 h stimulation period and analysed on a PRP-1 column by HPLC. The radioactive products were characterized by co-elution of (/sup 3/H) standard prostanoids. Osteoblasts showed a basal release of the prostanoids 6-keto-PGF1 alpha, TXB2, PGF2 alpha, PGE2, PGD2 and PGB2, the latter being the most abundant one. Indomethacin (10(-5) M) effectively inhibited the basal release, but not that of an as yet unidentified compound. The release of prostanoids was stimulated by PTH (2 U/ml), thrombin (0.4 NIH/ml), EGF (50 ng/ml) and PMA (25 ng/ml), the latter being by far the most potent one. 1,25-(OH)2D3 was found to slightly inhibit the prostanoid release. These results indicate: (1) primary cultures of osteoblasts synthesize several prostaglandins, thromboxane B2 and one unidentified product. (2) the action on bone of PTH and the various drugs tested may be, at least partly, mediated by an increased prostaglandin production by osteoblasts. Clearly this does not apply to 1,25-(OH)2D3.

  6. Generation of trans-arachidonic acid under nitrative stress is associated with upregulation of thromponsdin-1 in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    XU Lin; XU Xun; LIU Yu-min; YAO Zhu-jun; XUN Guo-liang; YU Wen-juan; LIU Kun; SUN Xiao-dong; QIU Yun-ping; WU Hai-xiang


    Background Trans-arachidonic acids (TAAs), newly discovered markers of nitrative stress and the major products of nitrogen dioxide (NO2)-mediated isomerization of arachidonic acid (AA), represent a new mechanism of NO2-induced toxicity. It has been reported that TAAs were generated in oxygen-induced microvascular degeneration model and TAAs were also generated in a diabetic retinopathy (DR) model. In this study, we examined high glucose-induced nitrative stress damage and TAAs levels and explored the possible mechanisms for DR caused by reactive nitrogen species. Methods Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ) at 60 mg/kg. Bovine retinal capillary endothelial cells (BRECs) were selectively cultured and incubated with normal or high glucose. The serum TAAs and AA in diabetic rats were measured by the gas chromatography and mass spectrometry (GC/MS) method. The ratio of peak area of TAAs to AA with selected ion of 79 was estimated by a group (-test. Thrombospondin-1 (TSP-1) in the rat retinas and BRECs extracts were examined by Western blotting. The phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) protein was examined by Western blotting in BRECs incubated with high glucose.Results The TAAs to AA ratio (TAAs/AA) was significantly increased in the serum at 8, 12 and 16 weeks after STZ injection (P 0.05). Expression of TSP-1 in the retina of diabetic rats was progressively elevated according to the duration of diabetes. TSP-1 expression was increased in BRECs incubated with high glucose at 48 hours. Moreover, high glucose also increased ERK1/2 expression, which peaked at 30 minutes and then decreased in the following 48 hours.Conclusion An elevation of TAAs/AA is associated with high glucose-induced nitrative stress, which probably involves upregulation of TSP-1 through activating ERK1/2.

  7. Cytochrome P450 CYP2J9, a new mouse arachidonic acid omega-1 hydroxylase predominantly expressed in brain. (United States)

    Qu, W; Bradbury, J A; Tsao, C C; Maronpot, R; Harry, G J; Parker, C E; Davis, L S; Breyer, M D; Waalkes, M P; Falck, J R; Chen, J; Rosenberg, R L; Zeldin, D C


    A cDNA encoding a new cytochrome P450 was isolated from a mouse brain library. Sequence analysis reveals that this 1,958-base pair cDNA encodes a 57-58-kDa 502-amino acid polypeptide that is 70-91% identical to CYP2J subfamily P450s and is designated CYP2J9. Recombinant CYP2J9 was co-expressed with NADPH-cytochrome P450 oxidoreductase (CYPOR) in Sf9 cells using a baculovirus system. Microsomes of CYP2J9/CYPOR-transfected cells metabolize arachidonic acid to 19-hydroxyeicosatetraenoic acid (HETE) thus CYP2J9 is enzymologically distinct from other P450s. Northern analysis reveals that CYP2J9 transcripts are present at high levels in mouse brain. Mouse brain microsomes biosynthesize 19-HETE. RNA polymerase chain reaction analysis demonstrates that CYP2J9 mRNAs are widely distributed in brain and most abundant in the cerebellum. Immunoblotting using an antibody raised against human CYP2J2 that cross-reacts with CYP2J9 detects a 56-kDa protein band that is expressed in cerebellum and other brain segments and is regulated during postnatal development. In situ hybridization of mouse brain sections with a CYP2J9-specific riboprobe and immunohistochemical staining with the anti-human CYP2J2 IgG reveals abundant CYP2J9 mRNA and protein in cerebellar Purkinje cells. Importantly, 19-HETE inhibits the activity of recombinant P/Q-type Ca(2+) channels that are known to be expressed preferentially in cerebellar Purkinje cells and are involved in triggering neurotransmitter release. Based on these data, we conclude that CYP2J9 is a developmentally regulated P450 that is abundant in brain, localized to cerebellar Purkinje cells, and active in the biosynthesis of 19-HETE, an eicosanoid that inhibits activity of P/Q-type Ca(2+) channels. We postulate that CYP2J9 arachidonic acid products play important functional roles in the brain.

  8. Arachidonic acid metabolism in TNS-induced chronic and immunologic enteritis in rats, and the effect of 5-ASA

    Directory of Open Access Journals (Sweden)

    F. J. Zijlstra


    Full Text Available Inflammation of the rat distal intestine was induced by intradermal sensitization and subsequent multiple intrajejunal challenge with the hapten 2,4,6-trinitrobenzenesulphonic acid (TNBS via an implanted catheter. The time course of the inflammatory reaction was followed by determination of the enteritis score and measurement of in vitro eicosanoid formation of homogenates of the gut after 0, 1, 2, 4, 7, 14 and 21 days of local daily challenge with 0.08% TNBS. There was a small initial increase of eicosanoid formation, reached at days 1 and 2, followed by a significant increase in metabolism of arachidonic acid on day 21. Although at day 1 a four-fold increase in inflammation score was reached, no further significant changes were observed during the following 3 weeks. The greatest increase in metabolite formation was observed in prostanoids TxB2, PGE2. and PGD2 and the 5-lipoxygenase product LTC4, whereas minor changes were found for LTB4 and other lipoxygenase products such as 12- and 15-HETE. The formation of these metabolites was already inhibited by low-dose 5-aminosalicylic acid (5-ASA, given orally twice daily during the 3 weeks challenge period, while the enteritis score was affected dosedependently.

  9. Mechanisms of formation and function of eosinophil lipid bodies: inducible intracellular sites involved in arachidonic acid metabolism

    Directory of Open Access Journals (Sweden)

    Bozza Patricia T


    Full Text Available Lipid bodies, inducible lipid-rich cytoplasmic inclusions, are characteristically abundant in cells associated with inflammation, including eosinophils. Here we reviewed the formation and function of lipid bodies in human eosinophils. We now have evidence that the formation of lipid bodies is not attributable to adverse mechanisms, but is centrally mediated by specific signal transduction pathways. Arachidonic acid and other cis fatty acids by an NSAID-inhibitable process, diglycerides, and PAF by a 5-lipoxygenase dependent pathway are potent stimulators of lipid body induction. Lipid body formation develops rapidly by processes that involve PKC, PLC, and de novo mRNA and protein synthesis. These structures clearly serve as repositoires of arachidonyl-phospholipids and are more than inert depots. Specific enzymes, including cytosolic phospholipase A2, MAP kinases, lipoxygenases and cyclooxygenases, associate with lipid bodies. Lipid bodies appear to be dynamic, organelle-like structures involved in intracellular pathways of lipid mobilization and metabolism. Indeed, increases in lipid body numbers correlated with enhanced production of both lipoxygenase- and cyclooxygenase-derived eicosanoids. We hypothesize that lipid bodies are distinct inducible sites for generating eicosanoids as paracrine mediators with varied activities in inflammation. The capacity of lipid body formation to be specifically and rapidly induced in leukocytes enhances eicosanoid mediator formation, and conversely pharmacologic inhibition of lipid body induction represents a potential novel and specific target for anti-inflammatory therapy.

  10. Effects of organometals on cellular signaling. I. Influence of metabolic inhibitors on metal-induced arachidonic acid liberation. (United States)

    Käfer, A; Krug, H F


    Organic lead and tin compounds stimulate an increase of free arachidonic acid (AA) in HL-60 cells. This fatty acid is involved in numerous health problems and physiological mechanisms. Three major pathways result in a liberation of AA from membrane phospholipids and there is evidence that G-proteins serve as couplers within all three pathways. Therefore we investigated the influence of pertussis toxin (PT) on the organometallic-induced AA liberation. The effect of all studied compounds (organotin and organo-lead) was diminished by PT. We conclude that the organometals activate PLA2 to some extent via a PT-sensitive pathway. The ionophor A 23187 (1-10 microM) led to an increase of free AA by raising the intracellular Ca2+ level. One of the postulated ways of AA release is via Ca2+ channel activation; phospholipases are Ca2+ dependent. Thus, we examined the necessity of free intracellular Ca2+ for the organometallic effect. The Ca2+ chelator EGTA inhibited the increase of free AA induced by organometals. This is true also for verapamil, a Ca2+ channel blocker. Quinacrine, which is thought to be an inhibitor of phospholipase A2 (PLA2), prevented the AA liberation from membrane phospholipids induced by organometals. This could be due to the inhibition of PLA2, but it could also be the result of an inhibited Ca2+ influx.

  11. Aureispira marina gen. nov., sp. nov., a gliding, arachidonic acid-containing bacterium isolated from the southern coastline of Thailand. (United States)

    Hosoya, Shoichi; Arunpairojana, Vullapa; Suwannachart, Chatrudee; Kanjana-Opas, Akkharawit; Yokota, Akira


    Three strains of gliding bacteria, 24(T), 62 and 71, isolated from a marine sponge and algae from the southern coastline of Thailand, were studied using a polyphasic approach to clarify their taxonomic positions. A phylogenetic analysis based on 16S rRNA gene sequences showed that the three isolates formed a distinct lineage within the family 'Saprospiraceae' of the phylum Bacteroidetes and were related to members of the genus Saprospira. The G+C contents of the isolates were in the range 38-39 mol%. The major respiratory quinone was MK-7. The predominant cellular fatty acids were 20 : 4omega6c (arachidonic acid), 16 : 0 and iso-17 : 0. On the basis of morphological, physiological and chemotaxonomic characteristics, together with DNA-DNA hybridization data and 16S rRNA gene sequences, the isolates represent a novel species of a novel genus, for which the name Aureispira marina gen. nov., sp. nov. is proposed. The type strain of Aureispira marina is 24(T) (=IAM 15389(T)=TISTR 1719(T)).

  12. Mechanism of angiotensin II-induced arachidonic acid metabolite release in aortic smooth muscle cells: involvement of phospholipase D. (United States)

    Shinoda, J; Kozawa, O; Suzuki, A; Watanabe-Tomita, Y; Oiso, Y; Uematsu, T


    In a previous study, we have shown that angiotensin II (Ang II) activates phosphatidylcholine-hydrolyzing phospholipase D due to Ang II-induced Ca2+ influx from extracellular space in subcultured rat aortic smooth muscle cells. In the present study, we have investigated the role of phospholipase D in Ang II-induced arachidonic acid (AA) metabolite release and prostacyclin synthesis in subcultured rat aortic smooth muscle cells. Ang II significantly stimulated AA metabolite release in a concentration-dependent manner in the range between 1 nmol/I and 0.1 mumol/I. D.L.-Propranolol hydrochloride (propranolol), an inhibitor of phosphatidic acid phosphohydrolase, significantly inhibited the Ang II-induced release of AA metabolites. The Ang II-induced AA metabolite release was reduced by chelating extracellular Ca2+ with EGTA. Genistein, an inhibitor of protein tyrosine kinases, significantly suppressed the Ang II-induced AA metabolite release. 1,6-Bis-(cyclohexyloximinocarbonylamino)-hexane (RHC-80267), a potent and selective inhibitor of diacylglycerol lipase, significantly inhibited the Ang II-induced AA metabolite release. Both propranolol and RHC-80267 inhibited the Ang II-induced synthesis of 6-keto-prostaglandin F1 alpha, a stable metabolite of prostacyclin. The synthesis was suppressed by genistein. These results strongly suggest that the AA metabolite release induced by Ang II is mediated, at least in part, through phosphatidylcholine hydrolysis by phospholipase D activation in aortic smooth muscle cells.

  13. The effects on plasma, red cell and platelet fatty acids of taking 12 g/day of ethyl-eicosapentaenoate for 16 months : dihomogammalinolenic, arachidonic and docosahexaenoic acids and relevance to Inuit metabolism

    NARCIS (Netherlands)

    Horrobin, David; Fokkema, M Rebecca; Muskiet, Frits A J


    A patient with mantle cell lymphoma took 12g/day of ethyl-eicosapentaenoate for 16 months. Compared to reference values, eicosapentaenoic and docosapentaenoic acids were elevated in plasma, red cells and platelets but docosahexaenoic acid levels were in the normal range. Arachidonic acid levels were

  14. Phospholipid, arachidonate and eicosanoid signaling in schizophrenia

    Directory of Open Access Journals (Sweden)

    Messamore Erik


    Full Text Available This paper reviews the potential role of arachidonic acid in the pathophysiology of schizophrenia. We discuss how abnormal levels of arachidonic acid may arise, and how dysregulation of signaling molecules derived from it have the potential to disrupt not only dopamine signaling, but numerous other physiological processes associated with the illness. Pharmacological doses of niacin stimulate the release of arachidonic acid; and arachidonic acid-derived molecules in turn dilate blood vessels in the skin. A blunted skin flush response to niacin is reliably observed among patients with schizophrenia. The niacin response abnormality may thus serve as a biomarker to identify a physiological subtype of schizophrenia associated with defective arachidonic acid-derived signaling.

  15. Arachidonic acid drives postnatal neurogenesis and elicits a beneficial effect on prepulse inhibition, a biological trait of psychiatric illnesses.

    Directory of Open Access Journals (Sweden)

    Motoko Maekawa

    Full Text Available Prepulse inhibition (PPI is a compelling endophenotype (biological markers for mental disorders including schizophrenia. In a previous study, we identified Fabp7, a fatty acid binding protein 7 as one of the genes controlling PPI in mice and showed that this gene was associated with schizophrenia. We also demonstrated that disrupting Fabp7 dampened hippocampal neurogenesis. In this study, we examined a link between neurogenesis and PPI using different animal models and exploring the possibility of postnatal manipulation of neurogenesis affecting PPI, since gene-deficient mice show biological disturbances from prenatal stages. In parallel, we tested the potential for dietary polyunsaturated fatty acids (PUFAs, arachidonic acid (ARA and/or docosahexaenoic acid (DHA, to promote neurogenesis and improve PPI. PUFAs are ligands for Fabp members and are abundantly expressed in neural stem/progenitor cells in the hippocampus. Our results are: (1 an independent model animal, Pax6 (+/- rats, exhibited PPI deficits along with impaired postnatal neurogenesis; (2 methylazoxymethanol acetate (an anti-proliferative drug elicited decreased neurogenesis even in postnatal period, and PPI defects in young adult rats (10 weeks when the drug was given at the juvenile stage (4-5 weeks; (3 administering ARA for 4 weeks after birth promoted neurogenesis in wild type rats; (4 raising Pax6 (+/- pups on an ARA-containing diet enhanced neurogenesis and partially improved PPI in adult animals. These results suggest the potential benefit of ARA in ameliorating PPI deficits relevant to psychiatric disorders and suggest that the effect may be correlated with augmented postnatal neurogenesis.

  16. COX-2, aspirin and metabolism of arachidonic, eicosapentaenoic and docosahexaenoic acids and their physiological and clinical significance. (United States)

    Poorani, R; Bhatt, Anant N; Dwarakanath, B S; Das, Undurti N


    Polyunsaturated fatty acids (PUFAs) are vital for normal growth and development and physiological function of various tissues in humans. PUFAs have immunomodulatory actions in addition to their ability to modulate inflammation, vascular reactivity, neurotransmission and stem cell biology. PUFAs and their metabolites possess both pro- and anti-inflammatory properties that underlie their actions and involvement in several diseases. Aspirin, a non-steroidal anti-inflammatory drug (NSAID), possesses both cyclo-oxygenase (COX) and lipoxygenase (LOX) inhibitory action and enhances the production of anti-inflammatory lipoxin A4 {(called as epi-lipoxin A4, aspirin-triggered lipoxins (ATLs))}. In addition, at low doses aspirin may not interfere with the production of prostacyclin (PGI2). Both lipoxin A4 and PGI2 have vasodilator, platelet anti-aggregator and anti-inflammatory actions that may underlie the beneficial actions of aspirin. Paradoxically, other NSAIDs may not have the same actions as that of aspirin on PUFA metabolism. Similar anti-inflammatory compounds are formed from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) by the action of aspirin termed as resolvins (from EPA and DHA) and protectins and maresins from DHA. PUFAs: arachidonic acid (AA), EPA and DHA and their various products modulate not only inflammation and immune response but also possess actions on various genes, nuclear factors, cyclic AMP and GMP, G-protein coupled receptors (GPRs), hypothalamic neurotransmitters, hormones, cytokines and enzymes, and interact with nitric oxide, carbon monoxide, and hydrogen sulfide to regulate their formation and action and to form new compounds that have several biological actions. These pleiotropic actions of PUFAs and their metabolites may explain their ability to play a role in several physiological actions and diseases. The big challenge is to harness these actions to prevent and manage clinical conditions.

  17. Upregulated expression of brain enzymatic markers of arachidonic and docosahexaenoic acid metabolism in a rat model of the metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Taha Ameer Y


    Full Text Available Abstract Background In animal models, the metabolic syndrome elicits a cerebral response characterized by altered phospholipid and unesterified fatty acid concentrations and increases in pro-apoptotic inflammatory mediators that may cause synaptic loss and cognitive impairment. We hypothesized that these changes are associated with phospholipase (PLA2 enzymes that regulate arachidonic (AA, 20:4n-6 and docosahexaenoic (DHA, 22:6n-6 acid metabolism, major polyunsaturated fatty acids in brain. Male Wistar rats were fed a control or high-sucrose diet for 8 weeks. Brains were assayed for markers of AA metabolism (calcium-dependent cytosolic cPLA2 IVA and cyclooxygenases, DHA metabolism (calcium-independent iPLA2 VIA and lipoxygenases, brain-derived neurotrophic factor (BDNF, and synaptic integrity (drebrin and synaptophysin. Lipid concentrations were measured in brains subjected to high-energy microwave fixation. Results The high-sucrose compared with control diet induced insulin resistance, and increased phosphorylated-cPLA2 protein, cPLA2 and iPLA2 activity and 12-lipoxygenase mRNA, but decreased BDNF mRNA and protein, and drebrin mRNA. The concentration of several n-6 fatty acids in ethanolamine glycerophospholipids and lysophosphatidylcholine was increased, as was unesterified AA concentration. Eicosanoid concentrations (prostaglandin E2, thromboxane B2 and leukotriene B4 did not change. Conclusion These findings show upregulated brain AA and DHA metabolism and reduced BDNF and drebrin, but no changes in eicosanoids, in an animal model of the metabolic syndrome. These changes might contribute to altered synaptic plasticity and cognitive impairment in rats and humans with the metabolic syndrome.

  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. Involvement of Oxidative Stress and Down-Regulation of Bcl-2 in Arachidonic Acid-Induced Apoptosis in HUVECs

    Institute of Scientific and Technical Information of China (English)

    WANG Bing-hua; WANG Yun; CHEN Li-da; CAO Jin-xiu; ZHOU Wen-jing


    Human umbilical vein endothelial cells (HUVECs) were treated with arachidonic acid (AA). After 24 h exposure to AA, typical morphological changes of apoptosis were observed by Giemsa stain and transmission electron microscopy. The apoptotic ratio in HUVECs treated with 50 μmol/L, 100 μmol/L and 150 μmol/L AA were (20.7±3.6) %, (38.6±4.3) % and (52.5±7.5) % respectively. Contrarily, low concentration of AA (≤25 μmol/L) exerted no influence on cell viability by MTT assay. Intracellular malondialdehyde increased significantly in a dose-dependent manner upon AA treatment and the opposite tendency was found for the reduced glutathione. Western Blots show that apoptosis triggered by AA was associated with the down-regulation of Bcl-2 expression, but not with Bax and p53. Pretreatment with 50 μmol/L α-tocopherol reduced AA-induced oxidative stress and apoptosis, also inhibited the down-regulation of Bcl-2/Bax ratio. These results suggested that high concentration of free AA could induce apoptosis in HUVECs probably via oxidative stress and down-regulation of Bcl-2.

  20. Lipid droplets in activated mast cells - a significant source of triglyceride-derived arachidonic acid for eicosanoid production. (United States)

    Dichlberger, Andrea; Schlager, Stefanie; Kovanen, Petri T; Schneider, Wolfgang J


    Mast cells are potent effectors of immune reactions and key players in various inflammatory diseases such as atherosclerosis, asthma, and rheumatoid arthritis. The cellular defense response of mast cells represents a unique and powerful system, where external signals can trigger cell activation resulting in a stimulus-specific and highly coordinated release of a plethora of bioactive mediators. The arsenal of mediators encompasses preformed molecules stored in cytoplasmic secretory granules, as well as newly synthesized proteinaceous and lipid mediators. The release of mediators occurs in strict chronological order and requires proper coordination between the endomembrane system and various enzymatic machineries. For the generation of lipid mediators, cytoplasmic lipid droplets have been shown to function as a major intracellular pool of arachidonic acid, the precursor for eicosanoid biosynthesis. Recent studies have revealed that not only phospholipids in mast cell membranes, but also triglycerides in mast cell lipid droplets are a substrate source for eicosanoid formation. The present review summarizes current knowledge about mast cell lipid droplet biology, and discusses expansions and challenges of traditional mechanistic models for eicosanoid production.

  1. The effect of antibiotic exposure on eicosanoid generation from arachidonic acid and gene expression in a primitive chordate, Branchiostoma belcheri. (United States)

    Yuan, Dongjuan; Pan, Minming; Zou, Qiuqiong; Chen, Chengyong; Chen, Shangwu; Xu, Anlong


    Chloramphenicol (Chl) is an effective antimicrobial agent widely used in veterinary medicine and commonly used in fish. Its use is restricted in the clinic because of adverse effects on the immune system and oxidative stress in mammals. However, the effects of Chl treatment on invertebrates remain unclear. Amphioxus, a basal chordate, is an ideal model to study the origin and evolution of the vertebrate immune system as it has a primary vertebrate-like arachidonic acid (AA) metabolic system. Here, we combined transcriptomic and lipidomic approaches to investigate the immune system and observe the oxygenated metabolites of AA to address the antibiotic effects on amphioxus. Tissue necrosis of the gill slits occurred in the Chl-treated amphioxus, but fewer epithelial cells were lost when treated with both Chl and ampicillin (Amp). The immune related pathways were dysregulated in both of the antibiotic treatment groups. The Chl alone treatment resulted in immunosuppression with down-regulation of the innate immune genes. In contrast, the Chl + Amp treatment resulted in immunostimulation to some extent, as shown by KEGG clustering. Furthermore, Chl induced a 3-fold reduction in the level of the eicosanoids, while the Chl + Amp treatment resulted in 1.7-fold increase of eicosanoid level. Thus in amphioxus, Amp might relieve the effects of the Chl-induced immune suppression and increase the level of eicosanoids from AA. Finally, the oxygenated metabolites from AA might be crucial to evaluate the effects of Chl treatment in animals.

  2. [Effect of dauricine on rat and human platelet aggregation and metabolism of arachidonic acid in washed rat platelets]. (United States)

    Tong, L; Yue, T L


    Dauricine (Dau), an isoquinoline alkaloid extracted from the roots of Menispermum dauricum D. C. and used as an antiarrhythmic agent in China recently, was shown to inhibit rat platelet aggregation induced by arachidonic acid (AA) and ADP, as well as human platelet aggregation induced by AA, ADP and adrenaline (Adr) in vitro in a dose-dependent manner. The concentration of Dau required for 50% inhibition (IC50) of rat platelet aggregation induced by AA and ADP was 26 and 37 mumol/L, respectively. For human platelet aggregation induced by AA, ADP and Adr the IC50 of Dau was found to be 39, 55 and 43 mumol/L, respectively. Dau inhibited the cyclooxygenase pathway metabolites of AA (TXB2 and HHT) in washed intact rat platelets. The production of TXB2 and HHT was reduced by 26% and 19%, respectively, when the Dau concentration was 50 mumol/L and by 46 and 45%, respectively, when the concentration of Dau was 100 mumol/L. The formation of 12-HETE was also inhibited at 100 mumol/L of Dau. The inhibitory effect of Dau on AA metabolism may be one of the mechanisms related to its inhibition of platelet aggregation.

  3. Production of arachidonic acid metabolites by macrophages exposed in vitro to asbestos, carbonyl iron particles, or calcium ionophore. (United States)

    Kouzan, S; Brody, A R; Nettesheim, P; Eling, T


    Consequent to asbestos deposition, alveolar macrophages (AM) accumulate at alveolar duct bifurcations where they phagocytize fibers. Because phagocytosis can stimulate the release of arachidonic acid (AA) metabolites, the possibility that secretion of these powerful mediators of inflammation might be induced by chrysotile asbestos was investigated in vitro. Rat AM were treated in vitro with chrysotile asbestos, and the cyclooxygenase products--prostaglandins, thromboxane B2 (TXB2), 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT)--and lipoxygenase products--leukotrienes (LT), hydroxyeicosatetraenoic acids (HETE)--secreted in the medium were isolated by high-performance liquid chromatography. Composition of the AA metabolites released was compared with that from those stimulated by the calcium ionophore A 23187 (20 microM) and by another particulate phagocytic stimulus, i.e., carbonyl iron beads. Calcium ionophore stimulation induced a marked release of various AA metabolites in the medium from both the cyclooxygenase pathway (HHT, TXB2, and PGE2, in decreasing quantities, respectively) and the lipoxygenase pathway (LTB4, 5-HETE, 12-HETE, and LTC4). The major product was LTB4. Treatment of the macrophages with asbestos fibers induced the release of a similar array of AA metabolites, although there were smaller amounts of LTC4 and 12-HETE, but increased quantities of PGF2 alpha. A time course study showed a steady increase in metabolite production for 1 h, followed by a plateau. In addition, the amount of metabolites released was dependent on asbestos concentrations. Phagocytosis of iron beads induced the secretion of the same metabolites as asbestos stimulation, but in larger quantities, probably reflecting the lack of cytotoxicity of the particle.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Hydroxyurea Therapy Mobilises Arachidonic Acid from Inner Cell Membrane Aminophospholipids in Patients with Homozygous Sickle Cell Disease

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    A. A. Daak


    Full Text Available The cytotoxic compound hydroxyurea (HU is effective therapy for sickle cell disease. However, its effect on unsaturated membrane lipids is unknown. Red cell fatty acids were investigated in HU-treated (n=19 and HU-untreated (n=17 sickle cell patients and controls (n=20. The HU-treated compared with the HU-untreated patients had lower arachidonic (AA acid level in ethanolamine, physphoglycerids (EPG (22.9±1.2   versus   24.0±1.1%,  P<0.05 serine SPG (22.13±2.2   versus   24.9±2.3%,  P<0.01 phosphoglycerides. The treated patients and controls had comparable levels of docosahexaenoic (DHA and total n-3 fatty acids in EPG and choline phosphoglycerides (CPG. In contrast, the untreated group had significantly (P<0.05 lower DHA and total n-3 compared with the controls in EPG (2.7±0.4   versus   3.2±0.6% and 4.6±0.5   versus   5.2±0.7% and CPG (0.7±0.2   versus   1.0±0.2% and 1.2±0.2   versus   1.4±0.3. HU is known to activate cytosolic phospholipase A2 and cyclooxygenase 2, and from this study, it appears to induce mobilisation of AA from the inner cell membrane EPG and SPG. Hence, eicosanoids generated from the released AA may play a role in clinical improvements which occur in HU-treated patients.

  5. Role of arachidonic acid in hyposmotic membrane stretch-induced increase in calcium-activated potassium currents in gastric myocytes

    Institute of Scientific and Technical Information of China (English)

    Meng YANG; Wen-xie XU; Xing-lan LI; Hui-ying XU; Jia-bin SUN; Bin MEI; Hai-feng ZHENG; Lian-hua PIAO; De-gang XING; Zhai-liu LI


    Aim: To study effects of arachidonic acid (AA) and its metabolites on the hyposmotic membrane stretch-induced increase in calcium-activated potassium currents (IKCa) in gastric myocytes. Methods: Membrane currents were recorded by using a conventional whole cell patch-clamp technique in gastric myocytes isolated with collagenase. Results: Hyposmotic membrane stretch and AA increased both IK(Ca) and spontaneous transient outward currents significantly.Exogenous AA could potentiate the hyposmotic membrane stretch-induced increase in IK(Ca). The hyposmotic membrane stretch-induced increase in IK(Ca) was significantly suppressed by dimethyleicosadienoic acid (100 μmol/L in pipette solution), an inhibitor of phospholipase A2. Nordihydroguaiaretic acid, a lipoxygenase inhibitor, significantly suppressed AA and hyposmotic membrane stretch-induced increases in IK(Ca). External calcium-free or gadolinium chloride, a blocker of stretch-activated channels, blocked the AA-induced increase in IK(Ca) significantly, but it was not blocked by nicardipine, an L-type calcium channel blocker. Ryanodine, a calcium-induced calcium release agonist, completely blocked the AA-induced increase in IK(Ca); however, heparin, a potent inhibitor of inositol triphosphate receptor, did not block the AA-induced increase in IK(Ca). Conclusion:Hyposmotic membrane stretch may activate phospholipase A2, which hydrolyzes membrane phospholipids to ultimately produce AA; AA as a second messenger mediates Ca2+ influx, which triggers Ca2+-induced Ca2+ release and elicits activation of IK(Ca) in gastric antral circular myocytes of the guinea pig.

  6. Effect of dietary fat saturation on lipid metabolism, arachidonic acid turnover and peritoneal macrophage oxidative stress in mice

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    L.B. Oliveros


    Full Text Available We investigated the effects of a saturated fat diet on lipid metabolism and arachidonic acid (AA turnover in mouse resident peritoneal macrophages. The pro-oxidative effect of this diet was also studied. Female C57BL/6 mice were weaned at 21 days of age and assigned to either the experimental diet containing coconut oil (COCO diet, or the control diet containing soybean oil as fat source (10 mice per group. The fat content of each diet was 15% (w/w. Mice were fed for 6 weeks and then sacrificed. The concentration of total lipids, triglycerides, (LDL + VLDL-cholesterol, thiobarbituric acid-reactive substances (TBARS and reduced glutathione were increased in the plasma of mice fed the COCO diet, without changes in phospholipid or total cholesterol concentrations compared to control. The concentrations of total cholesterol, free and esterified cholesterol, triglycerides, and TBARS were increased in the macrophages of COCO-fed mice, while the content of total phospholipids did not change. The phospholipid composition showed an increase of phosphatidylcholine and a decrease of phosphatidylethanolamine. The [³H]-AA distribution in the phospholipid classes showed an increase in phosphatidylcholine and phosphatidylethanolamine. Incorporation of [³H]-cholesterol into the macrophages of COCO-fed mice and into the cholesterol ester fraction was increased. The COCO diet did not affect [³H]-AA uptake but induced an increase in [³H]-AA release. The COCO diet also enhanced AA mobilization induced by lipopolysaccharide. These results indicate that the COCO diet, high in saturated fatty acids, alters the lipid metabolism and AA turnover of peritoneal macrophages in female mice and also produces a significant degree of oxidative stress.

  7. Food sources of arachidonic acid (PFA 20:4), listed in descending order by percentages of their contribution to intake, based on data from the National Health and Nutrition Examination Survey 2005-2006 (United States)

    Food sources of arachidonic acid (PFA 20:4), listed in descending order by percentages of their contribution to intake, based on data from the National Health and Nutrition Examination Survey 2005-2006

  8. Blockade by metal complexing agents and by catalase of the effects of arachidonic acid on platelets: relevance to the study of anti-inflammatory mechanisms. (United States)

    Vargaftig, B B; Tranier, Y; Chignard, M


    Metal-chelating agents inhibited platelet aggregation and the accompanying generation of rabbit aorta contracting and PG-like activities, when platelets were challenged with arachidonic acid. Inhibition required the presence of the chelating agents in the medium, and was insured by reagents avid for free or protein-bound copper. Catalase also prevented aggregation and generation of pharmacologically active substances; its activity was reversed by aminothiol agents and by Cu2+ and Zn2+, shown previously to potentiate the platelet effects of arachidonic acid. Inhibition by indomethacin was not prevented by amino-thiol drugs nor by Cu2+ or Zn2+. The catalase-induced inhibition was not affected by scavenging of thiol groups; this rules out, as a mechanism of action of catalase, the increased destruction of popoperoxides by glutathione peroxidase, which requires reduced glutathione as hydrogen donor. The results are compatible with the hypothesis that the agent that mediates platelet aggregation by arachidonic acid is a popoperoxide, requiring the presence either of H2O2 or of a similarly catalase-sensitive substance to be generated.

  9. Differential age- and disease-related effects on the expression of genes related to the arachidonic acid signaling pathway in schizophrenia. (United States)

    Tang, Bin; Capitao, Cristina; Dean, Brian; Thomas, Elizabeth A


    We have previously identified differential effects of age on global brain gene expression profiles in subjects with schizophrenia compared to normal controls. Here, we have focused on age-related effects of genes associated with the arachidonic acid-related inflammation pathway. Linear correlation analysis of published microarray expression data reveal strong age- and cell-type- specific-effects on the expression of genes related to the arachidonic acid signaling pathway, which differed in control subjects compared to those with schizophrenia. Using real-time qPCR analysis, we validated age and disease effects of arachidonic acid-related genes in a large cohort of subjects with schizophrenia and matched controls (n=76 subjects in total). We found that levels of prostaglandin-endoperoxide synthase 1 (PTGS1; aka COX-1) and prostaglandin-endoperoxide receptor 3 (PTGER3) mRNA are increased, and levels of prostaglandin-endoperoxide synthase 2 (PTGS2; aka COX-2) mRNA are decreased, in older subjects with schizophrenia (> 40years of age) compared to matched normal controls or younger subjects with schizophrenia (schizophrenia and further suggest that age may be an important factor in the potential use of anti-inflammatory therapies.

  10. The influence of dietary concentrations of arachidonic acid and eicosapentaenoic acid at various stages of larval ontogeny on eye migration, pigmentation and prostaglandin content of common sole larvae ( Solea solea L.)

    DEFF Research Database (Denmark)

    Lund, Ivar; Steenfeldt, Svend Jørgen; Banta, G.;


    Dietary manipulations of arachidonic acid, ARA and eicosapentaenoic acid, EPA may have an influence on pigmentation in common sole larvae (Solea solea L., Linnaeus 1758) which may be related to a "pigmentation window". This is a specific period in the larval ontogeny where nutritional factors...

  11. Novel liquid chromatography–mass spectrometry method shows that vitamin E deficiency depletes arachidonic and docosahexaenoic acids in zebrafish (Danio rerio embryos

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    Katie M. Lebold


    Full Text Available To test the hypothesis that embryogenesis depends upon α-tocopherol (E to protect embryo polyunsaturated fatty acids (PUFAs from lipid peroxidation, new methodologies were applied to measure α-tocopherol and fatty acids in extracts from saponified zebrafish embryos. A solid phase extraction method was developed to separate the analyte classes, using a mixed mode cartridge (reverse phase, π–π bonding, strong anion exchange, then α-tocopherol and cholesterol were measured using standard techniques, while the fatty acids were quantitated using a novel, reverse phase liquid chromatography–mass spectrometry (LC–MS approach. We also determined if α-tocopherol status alters embryonic lipid peroxidation products by analyzing 24 different oxidized products of arachidonic or docosahexaenoic (DHA acids in embryos using LC with hybrid quadrupole-time of flight MS. Adult zebrafish were fed E− or E+ diets for 4 months, and then were spawned to obtain E− and E+ embryos. Between 24 and 72 hours post-fertilization (hpf, arachidonic acid decreased 3-times faster in E− (21 pg/h compared with E+ embryos (7 pg/h, P<0.0001, while both α-tocopherol and DHA concentrations decreased only in E− embryos. At 36 hpf, E− embryos contained double the 5-hydroxy-eicosatetraenoic acids and 7-hydroxy-DHA concentrations, while other hydroxy-lipids remained unchanged. Vitamin E deficiency during embryogenesis depleted DHA and arachidonic acid, and increased hydroxy-fatty acids derived from these PUFA, suggesting that α-tocopherol is necessary to protect these critical fatty acids.

  12. Effect of some saturated and unsaturated fatty acids on prostaglandin biosynthesis in washed human blood platelets from (1-/sup 14/ C)arachidonic acid

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, K.C.; Awasthi, K.K.; Lindegard, P.; Tiwari, K.P.


    The effects of some saturated (lauric, palmitic and stearic) an unsaturated (linoleic, gamma-linolenic, alpha-linolenic and oleic) fatty acids at 0.1. 0.25 and 0.5 mM concentrations on the in vitro metabolization of (1-14 C) arachidonic acid by washed human blood platelets have been studied. Effects of these fatty acids were studied with intact as well as lysed platelet preparations. With intact platelet preparations it was found that (i) all unsaturated fatty acids enhanced the biosynthesis of TxB2, PGE2, PGD2 and PGF2 alpha, (ii) unsaturated fatty acids reduced the formation of HHT and HETE with the exception of oleic acid which showed very little effect, (iii) unsaturated fatty acids reduced the formation of MDA, whereas palmitic and stearic acids increased its formation and (iv) all unsaturated fatty acids reduced the synthesis of prostaglandin endoperoxides. These results support our previous observations where effects of fatty acids were examined at higher concentrations (10). At 0.1 mM FA concentration, inconsistent results were obtained. With lysed platelet preparations all cyclooxygenase products were reduced in presence of unsaturated fatty acids, whereas HETE formation was reduced only in presence of linoleic and gamma-linolenic acids. Electron micrographs of washed platelet suspensions were obtained with untreated platelet preparations and platelet preparations treated with 0.25 and 0.5 mM linoleic acid concentrations. The results are discussed in the light of a possible soap-like effect of FA salt on platelets.

  13. Associations between dietary n-6 and n-3 fatty acids and arachidonic acid compositions in plasma and erythrocytes in young and elderly Japanese volunteers

    Directory of Open Access Journals (Sweden)

    Kawabata Terue


    Full Text Available Abstract Background We reported that the compositions of arachidonic acid (ARA in erythrocytes and plasma phospholipids (PL in the elderly were lower than those in the young, though the ARA intake was nearly identical. Objective We further analyzed data in four study groups with different ages and sexes, and determined that the blood ARA levels were affected by the kinds of dietary fatty acids ingested. Methods One hundred and four healthy young and elderly volunteers were recruited. Dietary records together with photographic records from 28 consecutive days were reviewed and the fatty acid composition in plasma lipid fractions and erythrocyte PL was analyzed. Results No correlations for ARA between dietary fatty acids and blood lipid fractions were observed. A significant negative correlation between eicosapentaenoic acid (EPA + docosahexaenoic acid (DHA intake and ARA composition in erythrocyte PL was observed. ARA composition in erythrocyte PL was significantly lower in elderly subjects than in young subjects, because EPA and DHA intake in elderly subjects was higher than in young subjects. However, after removing the effect of dietary EPA+DHA intake, the ARA composition in erythrocyte PL in elderly subjects was significantly lower than that in young subjects. Conclusions Changes in physical conditions with aging influenced the low ARA composition of erythrocyte in elderly subjects in addition to the effects of dietary EPA and DHA.

  14. Pregnancy duration and the ratio of long-chain n-3 fatty acids to arachidonic acid in erythrocytes from Faroese women

    DEFF Research Database (Denmark)

    Olsen, S.F.; Hansen, Harald S.; Jensen, B.;


    of long-chain n-3 FA to arachidonic acid (the (3/6) ratio) was used as the most relevant single measure of exposure. In 18 women with certain gestational age and with spontaneous onset of delivery, gestational age was significantly associated with the (3/6) ratio quantified in PC (correlation coefficient...... 0.50, P = 0.035), but not with the (3/6) radio in PE (correlation coefficient 0.21, P = 0.40) or TL (correlation coefficient 0.29, P = 0.26). The association with the (3/6) ratio in PC could not be attributed to confounding by maternal age, weight, marital status or smoking....

  15. Mechanisms for the formation of isoprostane endoperoxides from arachidonic acid. "Dioxetane" intermediate versus beta-fragmentation of peroxyl radicals. (United States)

    Yin, Huiyong; Havrilla, Christine M; Gao, Ling; Morrow, Jason D; Porter, Ned A


    The isoprostanes are a class of autoxidation products generated from arachidonic acid (or its esters) by a free radical initiated process. The potent biological activity of these compounds has been attracting intense research interest since they were detected in humans as well as animal models in the early 1990s. The measurement of these compounds has been regarded as one of the most useful non-invasive biomarkers for oxidative stress status. Two mechanisms for the formation of these compounds have been proposed. In the first mechanism, a peroxyl radical undergoes successive 5-exo cyclizations analogous to the enzymatic mechanism proposed for prostaglandin biosynthesis. The second mechanism starts with a 4-exo cyclization of a peroxyl radical leading to an intermediate dioxetane, a mechanism that has also been proposed for prostaglandin biosynthesis as well as for the formation of 4-hydroxy nonenal (HNE). Autoxidation of cholesteryl-15-HpETE under free radical conditions provides Type IV isoprostanes. The "dioxetane" mechanism for isoprostane generation from 15-HpETE requires that optically pure products are formed from an optically pure reactant, whereas an alternate mechanism for the process involving beta-fragmentation of the 15-peroxyl would give racemic isoprostane products. We have carried out a test of the mechanism based upon these stereochemical requirements. The results of analysis of the product mixture derived from autoxidation of optically pure Ch-15-HpETE by atmospheric pressure chemical ionization-mass spectrometry coupled with chiral high performance liquid chromatography indicate that the major isoprostane diastereomers are formed as a racemic mixture. These experimental results are consistent with a mechanism for isoprostane formation involving beta-fragmentation of the 15-peroxyl radical followed by re-addition of oxygen to form the 11-HPETE peroxyl, and they exclude a mechanism proceeding through the formation of a dioxetane intermediate.

  16. Effects of Arachidonic Acid Supplementation on Acute Anabolic Signaling and Chronic Functional Performance and Body Composition Adaptations.

    Directory of Open Access Journals (Sweden)

    Eduardo O De Souza

    Full Text Available The primary purpose of this investigation was to examine the effects of arachidonic acid (ARA supplementation on functional performance and body composition in trained males. In addition, we performed a secondary study looking at molecular responses of ARA supplementation following an acute exercise bout in rodents.Thirty strength-trained males (age: 20.4 ± 2.1 yrs were randomly divided into two groups: ARA or placebo (i.e. CTL. Then, both groups underwent an 8-week, 3-day per week, non-periodized training protocol. Quadriceps muscle thickness, whole-body composition scan (DEXA, muscle strength, and power were assessed at baseline and post-test. In the rodent model, male Wistar rats (~250 g, ~8 weeks old were pre-fed with either ARA or water (CTL for 8 days and were fed the final dose of ARA prior to being acutely strength trained via electrical stimulation on unilateral plantar flexions. A mixed muscle sample was removed from the exercised and non-exercised leg 3 hours post-exercise.Lean body mass (2.9%, p<0.0005, upper-body strength (8.7%, p<0.0001, and peak power (12.7%, p<0.0001 increased only in the ARA group. For the animal trial, GSK-β (Ser9 phosphorylation (p<0.001 independent of exercise and AMPK phosphorylation after exercise (p-AMPK less in ARA, p = 0.041 were different in ARA-fed versus CTL rats.Our findings suggest that ARA supplementation can positively augment strength-training induced adaptations in resistance-trained males. However, chronic studies at the molecular level are required to further elucidate how ARA combined with strength training affect muscle adaptation.

  17. Ethanol Promotes Chemically Induced Oral Cancer in Mice through Activation of the 5-Lipoxygenase Pathway of Arachidonic Acid Metabolism (United States)

    Guo, Yizhu; Wang, Xin; Zhang, Xinyan; Sun, Zheng; Chen, Xiaoxin


    Alcohol drinking is a known risk factor for oral cancer in humans. However, previous animal studies on the promoting effect of ethanol on oral carcinogenesis were inconclusive. It is necessary to develop an animal model with which the molecular mechanism of ethanol-related oral carcinogenesis may be elucidated in order to develop effective prevention strategies. In this study, mice were first treated with 4-nitroquinoline-1-oxide (4NQO, 100μg/ml in drinking water) for 8 weeks, and then given water or ethanol (8%) as the sole drink for another 16 weeks. During the experiment, 8% ethanol was well tolerated by mice. The incidence of squamous cell carcinoma (SCC) increased from 20% (8/41) to 43% (17/40; p<0.05). Expression of 5-lipoxygenase (5-Lox) and cyclooxygenase 2 (Cox-2) was increased in dysplasia and SCC of 4NQO-treated tongues, and further enhanced by ethanol. Using this mouse model, we further demonstrated that fewer cancers were induced in Alox5−/− mice, as were cell proliferation, inflammation, and angiogenesis in the tongue, as compared with Alox5+/+ mice. Interestingly, Cox-2 expression was induced by ethanol in knockout mice, while 5-Lox and leukotriene A4 hydrolase (LTA4H) expression and leukotriene B4 (LTB4) biosynthesis were dramatically reduced. Moreover, ethanol enhanced expression and nuclear localization of 5-Lox and stimulated LTB4 biosynthesis in human tongue SCC cells (SCC-15 and SCC-4) in vitro. In conclusion, this study clearly demonstrated that ethanol promoted 4NQO-induced oral carcinogenesis, at least in part, through further activation of the 5-Lox pathway of arachidonic acid metabolism. PMID:21881027

  18. Platelet-activating factor induces phospholipid turnover, calcium flux, arachidonic acid liberation, eicosanoid generation, and oncogene expression in a human B cell line

    Energy Technology Data Exchange (ETDEWEB)

    Schulam, P.G.; Kuruvilla, A.; Putcha, G.; Mangus, L.; Franklin-Johnson, J.; Shearer, W.T. (Baylor College of Medicine, Houston, TX (USA))


    Platelet-activating factor is a potent mediator of the inflammatory response. Studies of the actions of platelet-activating factor have centered mainly around neutrophils, monocytes, and platelets. In this report we begin to uncover the influence of platelet-activating factor on B lymphocytes. Employing the EBV-transformed human B cell line SKW6.4, we demonstrate that platelet-activating factor significantly alters membrane phospholipid metabolism indicated by the incorporation of 32P into phosphatidylcholine, phosphatidylinositol, and phosphatidic acid but not significantly into phosphatidylethanolamine at concentrations ranging from 10(-9) to 10(-6) M. The inactive precursor, lyso-platelet-activating factor, at a concentration as high as 10(-7) M had no effect on any of the membrane phospholipids. We also show that platelet-activating factor from 10(-12) to 10(-6) M induced rapid and significant elevation in intracellular calcium levels, whereas lyso-platelet-activating factor was again ineffective. We further demonstrate the impact of platelet-activating factor binding to B cells by measuring platelet-activating factor induced arachidonic acid release and 5-hydroxyeicosatetraenoic acid production. Moreover, platelet-activating factor was capable of inducing transcription of the nuclear proto-oncogenes c-fos and c-jun. Finally we explored the possible role of 5-hydroxyeicosatetraenoic acid as a regulator of arachidonic acid liberation demonstrating that endogenous 5-lipoxygenase activity modulates platelet-activating factor induced arachidonic acid release perhaps acting at the level of phospholipase A2. In summary, platelet-activating factor is shown here to have a direct and profound effect on a pure B cell line.

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

    Directory of Open Access Journals (Sweden)

    Roberts Matthew A


    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.

  20. Low Na intake suppresses expression of CYP2C23 and arachidonic acid-induced inhibition of ENaC. (United States)

    Sun, Peng; Lin, Dao-Hong; Wang, Tong; Babilonia, Elisa; Wang, Zhijian; Jin, Yan; Kemp, Rowena; Nasjletti, Alberto; Wang, Wen-Hui


    We previously demonstrated that arachidonic acid (AA) inhibits epithelial Na channels (ENaC) through the cytochrome P-450 (CYP) epoxygenase-dependent pathway (34). In the present study, we tested the hypothesis that low Na intake suppresses the expression of CYP2C23, which is mainly responsible for converting AA to epoxyeicosatrienoic acid (EET) in the kidney (11) and attenuates the AA-induced inhibition of ENaC. Immunostaining showed that CYP2C23 is expressed in the Tamm-Horsfall protein (THP)-positive and aquaporin 2 (AQP2)-positive tubules. This suggests that CYP2C23 is expressed in the thick ascending limb (TAL) and collecting duct (CD). Na restriction significantly suppressed the expression of CYP2C23 in the TAL and CD. Western blot also demonstrated that the expression of CYP2C23 in renal cortex and outer medulla diminished in rats on Na-deficient diet (Na-D) but increased in those on high-Na diet (4%). Moreover, the content of 11,12-epoxyeicosatrienoic acid (EET) decreased in the isolated cortical CD from rats on Na-D compared with those on a normal-Na diet (0.5%). Patch-clamp study showed that application of 15 microM AA inhibited the activity of ENaC by 77% in the CCD of rats on a Na-D for 3 days. However, the inhibitory effect of AA on ENaC was significantly attenuated in rats on Na-D for 14 days. Furthermore, inhibition of CYP epoxygenase with MS-PPOH increased the ENaC activity in the CCD of rats on a control Na diet. We also used microperfusion technique to examine the effect of MS-PPOH on Na transport in the distal nephron. Application of MS-PPOH significantly increased Na absorption in the distal nephron of control rats but had no significant effect on Na absorption in rats on Na-D for 14 days. We conclude that low Na intake downregulates the activity and expression of CYP2C23 and attenuates the inhibitory effect of AA on Na transport.

  1. Leukotrienes and other lipoxygenase products of arachidonic acid synthesized in the kidney. (United States)

    Ardaillou, R; Baud, L; Sraer, J


    Lipoxygenase products are synthesized in the kidney. Rabbit medulla and murine and human glomeruli produce 12- and 15-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE). Minor amounts of leukotrienes are formed under normal conditions, but it is likely that the resident renal cells are capable of synthesizing these metabolites. Rat glomeruli and papillae possess the enzymes necessary to process leukotriene C4 into leukotrienes D4 and E4. However, the enzyme activity of the papillae is masked due to the presence of an inhibitor detected in the 10,000 g supernate of the papillary homogenate. 12-HETE synthesis is markedly increased in glomeruli from rats with nephrotoxic serum nephritis and leukotriene B4 synthesis in glomeruli from rats with cationic bovine gamma-globulin-induced glomerulonephritis. In vivo consequences of the association between the resident glomerular cells and the bone marrow-derived cells have been studied in vitro in co-incubation experiments. Glomeruli release factors that stimulate the cyclo-oxygenase and lipoxygenase pathways in macrophages. Co-incubation of glomeruli, platelets, and polymorphonuclear leukocytes results in the formation of 12,20-diHETE and an excess of 12-HETE. Lipoxygenase products, regardless of their origin, modify the renal functions. Leukotriene C4 binds specifically to rat glomeruli and human cultured glomerular epithelial cells. Leukotrienes C4 or D4 administered in vivo cause renal vasoconstriction and a decline in the glomerular filtration rate. In vitro, these two sulfidopeptide leukotrienes promote epithelial cell proliferation and produce mesangial cell contraction. The lipoxygenase pathway is also implicated in the attachment of macrophages to glomeruli and in the oxidative burst of glomerular mesangial cells during phagocytosis. The future use of specific inhibitors of the synthesis or antagonists of the lipoxygenase products, particularly the leukotrienes, should provide a tool for evaluating the role of these

  2. Arachidonic acid has a dominant effect to regulate lipogenic genes in 3T3-L1 adipocytes compared to omega-3 fatty acids

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    Hitesh Vaidya


    Full Text Available Background: The effects of long-chain n-3 and n-6 polyunsaturated fatty acids (PUFA on the regulation of adipocytes metabolism are well known. These fatty acids are generally consumed together in our diets; however, the metabolic regulation of adipocytes in the presence of these fatty acids when given together is not known. Objective: To investigate the effects of n-3 PUFA and arachidonic acid (AA, an n-6 PUFA, on the regulation of adipogenic and lipogenic genes in mature 3T3-L1 adipocytes. Methods: 3T3-L1 adipocytes were incubated in the presence or absence of 100 µM of eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA; docosapentaenoic acid, DPA and AA, either alone or AA+n-3 PUFA; control cells received bovine serum albumin alone. The mRNA expression of adipogenic and lipogenic genes was measured. The fatty acid composition of adipocytes was analyzed using gas chromatography. Results: Individual n-3 PUFA or AA had no effect on the mRNA expression of peroxisome-proliferator-activated receptor-γ; however, AA+EPA and AA+DPA significantly increased (P<0.05 the expression compared to control cells (38 and 42%, respectively. AA and AA+EPA increased the mRNA expression of acetyl-CoA carboxylase 1 (P<0.05. AA treatment decreased the mRNA expression of stearoyl-CoA desaturase (SCD1 (P<0.01, while n-3 PUFA, except EPA, had no effect compared to control cells. AA+DHA and AA+DPA inhibited SCD1 gene expression (P<0.05 suggesting a dominant effect of AA. Fatty acids analysis of adipocytes revealed a higher accretion of AA compared to n-3 PUFA. Conclusions: Our findings reveal that AA has a dominant effect on the regulation of lipogenic genes in adipocytes.

  3. Arachidonic acid triggers [Ca2+]i increases in rat round spermatids by a likely GPR activation, ERK signalling and ER/acidic compartments Ca2+ release (United States)

    Paillamanque, Joaquin; Sanchez-Tusie, Ana; Carmona, Emerson M.; Treviño, Claudia L.; Sandoval, Carolina; Nualart, Francisco; Osses, Nelson


    Arachidonic acid (AA), a compound secreted by Sertoli cells (SC) in a FSH-dependent manner, is able to induce the release of Ca2+ from internal stores in round spermatids and pachytene spermatocytes. In this study, the possible site(s) of action of AA in round spermatids, the signalling pathways associated and the intracellular Ca2+ stores targeted by AA-induced signalling were pharmacologically characterized by measuring intracellular Ca2+ using fluorescent Ca2+ probes. Our results suggest that AA acts by interacting with a fatty acid G protein coupled receptor, initiating a G protein signalling cascade that may involve PLA2 and ERK activation, which in turn opens intracellular ryanodine-sensitive channels as well as NAADP-sensitive channels in acidic intracellular Ca2+ stores. The results presented here also suggest that AMPK and PKA modulate this AA-induced Ca2+ release from intracellular Ca2+ stores in round spermatids. We propose that unsaturated free fatty acid lipid signalling in the seminiferous tubule is a novel regulatory component of rat spermatogenesis. PMID:28192519

  4. Competitive Interaction Between Plasma Omega-3 Fatty Acids and Arachidonic Acid is Related to Down-Regulation of A Signaling Mediator. (United States)

    Yui, Kunio; Imataka, George; Kawasaki, Yohei


    Autism spectrum disorders (ASD) may be attributed to altered composition of polyunsaturated fatty acids. We examined the relationships between the plasma ratios of docosahexaenoic acid (DHA)/arachidonic acid (AA) and eicosapentaenoic acid (EPA)/AA, and biomarkers of AA-related signaling mediators, i.e., ceruloplasmin, transferrin and superoxide dismutase, with the behavioral symptoms of 30 individuals with ASD (mean age, 13.0 years old) and 20 age- and gender-matched normal controls (mean age, 13.6 years old). Behavioral symptoms were assessed using the Aberrant Behavior Checklists (ABC). The ASD group had significantly higher plasma DHA/AA and EPA/AA ratios, as well as ABC scores, compared to the control group. The plasma ceruloplasmin levels in the ASD group were significantly reduced compared to those in the control group. Multiple linear regression demonstrated that plasma DHA/AA ratio was a fitting model for distinguishing the ASD group from the control group. These findings suggested that increased plasma DHA/AA ratio may be related to lower plasma levels of ceruloplasmin, which may contribute to the pathophysiology of behavioral symptoms in 30 individuals with ASD.

  5. Long-term modifications of blood pressure in normotensive and spontaneously hypertensive rats by gene delivery of rAAV-mediated cytochrome P450 arachidonic acid hydroxylase

    Institute of Scientific and Technical Information of China (English)


    Arachidonic acid cytochrome P-450 (CYP) hydroxylase 4A isoforms, including 4A1, 4A2, 4A3 and 4A8 in the rat kidney, catalyze arachidonic acid to produce 19/20-Hydroxyeicosatetraenoic acids (20-HETE), a biologically active metabolite, which plays an important role in the regulation of blood pressure. However, controversial results have been reported regarding the exact role of 20-HETE on blood pressure. In the present study, we used recombinant adenoassociated viral vector (rAAV) to deliver CYP 4A1 cDNA and antisense 4A1 cDNA into Sprague-Dawley (SD) rats and spontaneously hypertensive rats (SHR), respectively, to investigate the effects of long-term modifications of blood pressure and the potential for gene therapy of hypertension. The mean systolic pressure increased by 14.2±2.5 mm Hg in rAAV.4A1-treated SD rats and decreased by 13.7±2.2 mm Hg in rAAV.anti4A1-treated SHR rats 5 weeks after the injection compared with controls and these changes in blood pressure were maintained until the experiments ended at 24weeks. In 4A1 treated animals CYP4A was overexpressed in various tissues, but preferentially in the kidney at both mRNA and protein levels. In anti-4A1-treated SHR, CYP4A mRNA in various tissues was probed, especially in kidneys,but 4A1 protein expression was almost completely inhibited. These results suggest that arachidonic acid CYP hydroxylases contribute not only to the maintenance of normal blood pressure but also to the development of hypertension.rAAV-mediated anti4A administration strategy has the potential to be used as targeted gene therapy in human hypertension by blocking expression of CYP 4A in kidneys.

  6. Interrelated effects of dihomo-γ-linolenic and arachidonic acids, and sesamin on hepatic fatty acid synthesis and oxidation in rats. (United States)

    Ide, Takashi; Ono, Yoshiko; Kawashima, Hiroshi; Kiso, Yoshinobu


    Interrelated effects of dihomo-γ-linolenic acid (DGLA) and arachidonic acid (ARA), and sesamin, a sesame lignan, on hepatic fatty acid synthesis and oxidation were examined in rats. Rats were fed experimental diets supplemented with 0 or 2 g/kg sesamin (1:1 mixture of sesamin and episesamin), containing 100 g/kg of maize oil or fungal oil rich in DGLA or ARA for 16 d. Among the groups fed sesamin-free diets, oils rich in DGLA or ARA, especially the latter, compared with maize oil strongly reduced the activity and mRNA levels of various lipogenic enzymes. Sesamin, irrespective of the type of fat, reduced the parameters of lipogenic enzymes except for malic enzyme. The type of dietary fat was rather irrelevant in affecting hepatic fatty acid oxidation among rats fed the sesamin-free diets. Sesamin increased the activities of enzymes involved in fatty acid oxidation in all groups of rats given different fats. The extent of the increase depended on the dietary fat type, and the values became much higher with a diet containing sesamin and oil rich in ARA in combination than with a diet containing lignan and maize oil. Analyses of mRNA levels revealed that the combination of sesamin and oil rich in ARA compared with the combination of lignan and maize oil markedly increased the gene expression of various peroxisomal fatty acid oxidation enzymes but not mitochondrial enzymes. The enhancement of sesamin action on hepatic fatty acid oxidation was also confirmed with oil rich in DGLA but to a lesser extent.

  7. Effects of naturally occurring dihydroflavonols from Inula viscosa on inflammation and enzymes involved in the arachidonic acid metabolism. (United States)

    Hernández, Victoriano; Recio, M Carmen; Máñez, Salvador; Giner, Rosa M; Ríos, José-Luis


    The anti-inflammatory properties of three flavanones isolated from Inula viscosa, sakuranetin, 7-O-methylaromadendrin, and 3-acetyl-7-O-methylaromadendrin, have been tested both in vitro and in vivo. Acute inflammation in vivo was induced by means of topical application of 12-O-tetradecanoylphorbol 13-acetate (TPA) to mouse ears or by subcutaneous injection of phospholipase A(2) (PLA(2)) into mouse paws. The test compounds were evaluated in vitro for their effect on both the metabolism of arachidonic acid and on the release and/or activity of enzymes involved in the inflammatory response such as elastase, myeloperoxidase (MPO), and protein kinase C (PKC). The most active compounds in vivo against PLA(2)-induced paw oedema were 7-O-methylaromadendrin (ED(50)=8 mg/kg) and sakuranetin (ED(50)=18 mg/kg). In contrast, the most potent compound against TPA-induced ear oedema was 3-acetyl-7-O-methylaromadendrin (ED(50)=185 microg/ear), followed by sakuranetin (ED(50)=205 microg/ear). In vitro, the latter compound was the most potent inhibitor of leukotriene (LT) B(4) production by peritoneal rat neutrophils (IC(50)=9 microM) and it was also the only compound that directly inhibited the activity of 5-lipoxygenase (5-LOX). 3-Acetyl-7-O-methylaromadendrin also inhibited LTB(4) production (IC(50)=15 microM), but had no effect on 5-LOX activity. The only flavanone that inhibited the secretory PLA(2) activity in vitro was 7-O-methylaromadendrin. This finding may partly explain the anti-inflammatory effect observed in vivo, although other mechanisms such as the inhibition of histamine release by mast cells may also be implicated. Sakuranetin at 100 microM was found to inhibit elastase release, although this result is partly due to direct inhibition of the enzyme itself. At the same concentration, 7-O-methylaromadendrin only affected the enzyme release. Finally, none of the flavanones exhibited any effect on MPO or PKC activities. Taken together, these findings indicate that


    Institute of Scientific and Technical Information of China (English)


    The changes in arachidonic acid (AA) and fatty acids profiles along the growth curve of Parietochloris incisa, a coccoid snow green alga, were studied in a 2.8 cm light-path flat photobioreactor, exposed to strong photon flux density [PFD, 2400 μEmol/(m2*s)]. Sixteen fatty acids were identified by gas chromatography showing that AA was the dominant fatty acid (33%-41%) followedby linoleic acid (17%-21%). AA content was closely investigated with respect tototal fatty acids (TFA), ash free dry weight (AFDW) of cell mass as well as total culture content. These parameters were influenced significantly in a similar manner by culture growth phase, i.e., slightly decreasing in the lag period, gradually increasing in the logarithmic phase, becoming maximal at the early stationary phase, starting to decrease at the late stationary phase, sharply dropping at the decline phase. The increase in AA per culture volume during the logarithmic phase was not only associated with the increase in AFDW but also connected with a corresponding increase in AA/TFA, TFA/AFDW as well as AA/AFDW. The sharp decrease in AA content of the culture during the decline phase was mainly due to the decrease in AA/TFA, TFA/AFDW and AA/AFDW, although AFDW declined only a smallextent. Maximal AA concentration, obtained at the early stationary phase, was 900 mg/L culture volume, and the average daily net increase of AA during 9 days logarithmic growth was 1.7 g/(m2*day). Therefore, harvesting prior to the declinephase in a batch culture, or at steady state in continuous culture mode seems best for high AA production. The latter possibility was also further confirmed bycontinuous culture with 5 gradients of harvesting rate. ``

  9. An Optimized High Throughput Clean-Up Method Using Mixed-Mode SPE Plate for the Analysis of Free Arachidonic Acid in Plasma by LC-MS/MS. (United States)

    Wang, Wan; Qin, Suzi; Li, Linsen; Chen, Xiaohua; Wang, Qunjie; Wei, Junfu


    A high throughput sample preparation method was developed utilizing mixed-mode solid phase extraction (SPE) in 96-well plate format for the determination of free arachidonic acid in plasma by LC-MS/MS. Plasma was mixed with 3% aqueous ammonia and loaded into each well of 96-well plate. After washing with water and methanol sequentially, 3% of formic acid in acetonitrile was used to elute arachidonic acid. The collected fraction was injected onto a reversed phase column at 30°C with mobile phase of acetonitrile/water (70 : 30, v/v) and detected by LC-MS/MS coupled with electrospray ionization (ESI) in multiple reaction monitoring (MRM) mode. The calibration curve ranged from 10 to 2500 ng/mL with sufficient linearity (r (2) = 0.9999). The recoveries were in the range of 99.38% to 103.21% with RSD less than 6%. The limit of detection is 3 ng/mL.

  10. A quantitiative LC-MS/MS method for the measurement of arachidonic acid, prostanoids, endocannabinoids, N-acylethanolamines and steroids in human plasma. (United States)

    Gachet, María Salomé; Rhyn, Peter; Bosch, Oliver G; Quednow, Boris B; Gertsch, Jürg


    Free arachidonic acid is functionally interlinked with different lipid signaling networks including those involving prostanoid pathways, the endocannabinoid system, N-acylethanolamines, as well as steroids. A sensitive and specific LC-MS/MS method for the quantification of arachidonic acid, prostaglandin E2, thromboxane B2, anandamide, 2-arachidonoylglycerol, noladin ether, lineoyl ethanolamide, oleoyl ethanolamide, palmitoyl ethanolamide, steroyl ethanolamide, aldosterone, cortisol, dehydroepiandrosterone, progesterone, and testosterone in human plasma was developed and validated. Analytes were extracted using acetonitrile precipitation followed by solid phase extraction. Separations were performed by UFLC using a C18 column and analyzed on a triple quadrupole MS with electron spray ionization. Analytes were run first in negative mode and, subsequently, in positive mode in two independent LC-MS/MS runs. For each analyte, two MRM transitions were collected in order to confirm identity. All analytes showed good linearity over the investigated concentration range (r>0.98). Validated LLOQs ranged from 0.1 to 190ng/mL and LODs ranged from 0.04 to 12.3ng/mL. Our data show that this LC-MS/MS method is suitable for the quantification of a diverse set of bioactive lipids in plasma from human donors (n=32). The determined plasma levels are in agreement with the literature, thus providing a versatile method to explore pathophysiological processes in which changes of these lipids are implicated.

  11. Exogenous arachidonic acid mediates permeability of human brain microvessel endothelial cells through prostaglandin E2 activation of EP3 and EP4 receptors. (United States)

    Dalvi, Siddhartha; Nguyen, Hieu H; On, Ngoc; Mitchell, Ryan W; Aukema, Harold M; Miller, Donald W; Hatch, Grant M


    The blood-brain barrier, formed by microvessel endothelial cells, is the restrictive barrier between the brain parenchyma and the circulating blood. Arachidonic acid (ARA; 5,8,11,14-cis-eicosatetraenoic acid) is a conditionally essential polyunsaturated fatty acid [20:4(n-6)] and is a major constituent of brain lipids. The current study examined the transport processes for ARA in confluent monolayers of human brain microvascular endothelial cells (HBMEC). Addition of radioactive ARA to the apical compartment of HBMEC cultured on Transwell(®) inserts resulted in rapid incorporation of radioactivity into the basolateral medium. Knock down of fatty acid transport proteins did not alter ARA passage into the basolateral medium as a result of the rapid generation of prostaglandin E2 (PGE2 ), an eicosanoid known to facilitate opening of the blood-brain barrier. Permeability following ARA or PGE2 exposure was confirmed by an increased movement of fluorescein-labeled dextran from apical to basolateral medium. ARA-mediated permeability was attenuated by specific cyclooxygenase-2 inhibitors. EP3 and EP4 receptor antagonists attenuated the ARA-mediated permeability of HBMEC. The results indicate that ARA increases permeability of HBMEC monolayers likely via increased production of PGE2 which acts upon EP3 and EP4 receptors to mediate permeability. These observations may explain the rapid influx of ARA into the brain previously observed upon plasma infusion with ARA. The blood-brain barrier, formed by microvessel endothelial cells, is a restrictive barrier between the brain parenchyma and the circulating blood. Radiolabeled arachidonic acid (ARA) movement across, and monolayer permeability in the presence of ARA, was examined in confluent monolayers of primary human brain microvessel endothelial cells (HBMECs) cultured on Transwell(®) plates. Incubation of HBMECs with ARA resulted in a rapid increase in HBMEC monolayer permeability. The mechanism was mediated, in part

  12. The effect of trinitrobenzene sulfonic acid on gut-derived smooth muscle cell arachidonic acid metabolism: role of endogenous prostanoids

    Directory of Open Access Journals (Sweden)

    W. E. Longo


    Full Text Available The contribution of smooth muscle cells as a potential source of eicosanoid production during inflammatory states remains to be elucidated. We investigated the effect of trinitrobenzene sulfonic acid (TNB, a known pro-inflammatory agent, on jejunal smooth muscle cell eicosanoid production. Human gut-derived smooth muscle cells (HISM were incubated with TNB for 1 hour. Additionally, some cells were preincubated with either dimethylthiourea, or indomethacin for 1 hour before exposure to identical concentrations of TNB. Incubation with TNB led to significant increases in PGE2 and 6-keto PGF-1α release, but not leukotriene B4 release; responses which were both inhibited by dimethylthiourea and indomethacin treatment. Our results suggest that gutderived smooth muscle cells may represent an important source of proinflammatory prostanoids but not leukotrienes during inflammatory states of the intestine. The inhibition of prostanoid activity by thiourea may be mediated by suppression of cyclooxygenase activity in this cell line.

  13. The effect of non-steroidal anti-inflammatory drugs on the metabolism of /sup 14/C-arachidonic acid by human gingival tissue in vitro

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    Elattar, T.M.; Lin, H.S.; Tira, D.E.


    We investigated the effect of non-steroidal anti-inflammatory drugs on prostaglandins (PGs) and 12-hydroxyeicosatetraenoic acid (12-HETE) formation by inflamed human gingival tissues. Gingival tissue homogenates were incubated with /sup 14/C-arachidonic acid in the presence of indomethacin, piroxicam, or ibuprofen, and the organic solvent extracts were chromatographed on silica gel plates with standards for radiometric assay. There was a significant negative trend between the doses (10(-7)-10(-3) M) of each of indomethacin, piroxicam, and ibuprofen, and the amounts of PGF2 alpha, PGE2, PGD2, and 15-keto-PGE2 produced. All three drugs have a significant inhibitory effect on PGs and 12-HETE production at 10(-3) M when compared with the control. The rank order effectiveness of the drugs, at 10(-3) M, on PG inhibition was indomethacin greater than piroxicam greater than ibuprofen, and on 12-HETE inhibition was indomethacin greater than ibuprofen greater than piroxicam.

  14. Arachidonate metabolism in bovine gallbladder muscle

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    Nakano, M.; Hidaka, T.; Ueta, T.; Ogura, R.


    Incubation of (1-/sup 14/C)arachidonic acid (AA) with homogenates of bovine gallbladder muscle generated a large amount of radioactive material having the chromatographic mobility of 6-keto-PGF1 alpha (stable product of PGI2) and smaller amounts of products that comigrated with PGF2 alpha PGE2. Formation of these products was inhibited by the cyclooxygenase inhibitor indomethacin. The major radioactive product identified by thin-layer chromatographic mobility and by gas chromatography - mass spectrometric analysis was found to be 6-keto-PGF1 alpha. The quantitative metabolic pattern of (1-/sup 14/C)PGH2 was virtually identical to that of (1-/sup 14/C)AA. Incubation of arachidonic acid with slices of bovine gallbladder muscle released labile anti-aggregatory material in the medium, which was inhibited by aspirin or 15-hydroperoxy-AA. These results indicate that bovine gallbladder muscle has a considerable enzymatic capacity to produce PGI2 from arachidonic acid.

  15. Isoliquiritigenin induces growth inhibition and apoptosis through downregulating arachidonic acid metabolic network and the deactivation of PI3K/Akt in human breast cancer

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    Li, Ying; Zhao, Haixia [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Wang, Yuzhong [Key Laboratory for Oral Biomedical Engineering of Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan 430079 (China); Zheng, Hao; Yu, Wei; Chai, Hongyan [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Zhang, Jing [Animal Experimental Center of Wuhan University, Wuhan 430071 (China); Falck, John R. [Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390,USA (United States); Guo, Austin M. [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Department of Pharmacology, New York Medical College, Valhalla, NY 10595 (United States); Yue, Jiang; Peng, Renxiu [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Yang, Jing, E-mail: [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)


    Arachidonic acid (AA)-derived eicosanoids and its downstream pathways have been demonstrated to play crucial roles in growth control of breast cancer. Here, we demonstrate that isoliquiritigenin, a flavonoid phytoestrogen from licorice, induces growth inhibition and apoptosis through downregulating multiple key enzymes in AA metabolic network and the deactivation of PI3K/Akt in human breast cancer. Isoliquiritigenin diminished cell viability, 5-bromo-2′-deoxyuridine (BrdU) incorporation, and clonogenic ability in both MCF-7 and MDA-MB-231cells, and induced apoptosis as evidenced by an analysis of cytoplasmic histone-associated DNA fragmentation, flow cytometry and hoechst staining. Furthermore, isoliquiritigenin inhibited mRNA expression of multiple forms of AA-metabolizing enzymes, including phospholipase A2 (PLA2), cyclooxygenases (COX)-2 and cytochrome P450 (CYP) 4A, and decreased secretion of their products, including prostaglandin E{sub 2} (PGE{sub 2}) and 20-hydroxyeicosatetraenoic acid (20-HETE), without affecting COX-1, 5-lipoxygenase (5-LOX), 5-lipoxygenase activating protein (FLAP), and leukotriene B{sub 4} (LTB{sub 4}). In addition, it downregulated the levels of phospho-PI3K, phospho-PDK (Ser{sup 241}), phospho-Akt (Thr{sup 308}), phospho-Bad (Ser{sup 136}), and Bcl-x{sub L} expression, thereby activating caspase cascades and eventually cleaving poly(ADP-ribose) polymerase (PARP). Conversely, the addition of exogenous eicosanoids, including PGE{sub 2}, LTB{sub 4} and a 20-HETE analog (WIT003), and caspase inhibitors, or overexpression of constitutively active Akt reversed isoliquiritigenin-induced apoptosis. Notably, isoliquiritigenin induced growth inhibition and apoptosis of MDA-MB-231 human breast cancer xenografts in nude mice, together with decreased intratumoral levels of eicosanoids and phospho-Akt (Thr{sup 308}). Collectively, these data suggest that isoliquiritigenin induces growth inhibition and apoptosis through downregulating AA metabolic

  16. Targeted profiling of arachidonic acid and eicosanoids in rat tissue by UFLC-MS/MS: Application to identify potential markers for rheumatoid arthritis. (United States)

    Wang, Nannan; Zhao, Xiaoning; Wang, Weihui; Peng, Yan; Bi, Kaishun; Dai, Ronghua


    We describe a method for the targeted analysis of bioactive arachidonic acid metabolites through cyclooxygenase (COX) and lipoxygenase (LOX) pathway in knee joint, liver, kidney, spleen and heart using an ultra-fast liquid chromatography-tandem mass (UFLC-MS/MS) method. Method validation was investigated, including linearity, precision, accuracy, matrix effect, extraction recovery and stability for the simultaneous analysis of prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs) and hydroxyeicosatetraenoic acids (HETEs). The method enables us to chromatographically separate branched-chain species from their straight-chain isomers as well as separate biologically important eicosanoids. The concentrations of the following major eicosanoids were significantly increased in rheumatoid arthritis model rats than in normal ones: 5-HETE, 8-HETE, 12-HETE, 15-HETE, PGF2α, TXB2, 5-HpETE, LTE4, PGE2, PGD2, LTB4. Further multivariate data analysis (partial least square-discriminant analysis) showed COX products (PGs, TXs) were readily distributed towards liver and kidney, LOX products (LTs, HETEs) towards knee joint and spleen, and heart had no characteristic metabolites. The method described here offers a useful tool for the evaluation of complex regulatory eicosanoids responses in RA disease states and provides support for use of dual inhibitors of COX and LOX enzymes on RA treatment.

  17. Analysis of cytochrome P450 metabolites of arachidonic acid by stable isotope probe labeling coupled with ultra high-performance liquid chromatography/mass spectrometry. (United States)

    Zhu, Quan-Fei; Hao, Yan-Hong; Liu, Ming-Zhou; Yue, Jiang; Ni, Jian; Yuan, Bi-Feng; Feng, Yu-Qi


    Cytochrome P450 metabolites of arachidonic acid (AA) belong to eicosanoids and are potent lipid mediators of inflammation. It is well-known that eicosanoids play an important role in numerous pathophysiological processes. Therefore, quantitative analysis of cytochrome P450 metabolites of AA, including hydroxyeicosatetraenoic acids (HETEs), epoxyeicosatreinoic acids (EETs), and dihydroxyeicosatrienoic acids (DHETs) can provide crucial information to uncover underlying mechanisms of cytochrome P450 metabolites of AA related diseases. Herein, we developed a highly sensitive method to identify and quantify HETEs, EETs, and DHETs in lipid extracts of biological samples based on stable isotope probe labeling coupled with ultra high-performance liquid chromatography/mass spectrometry. To this end, a pair of stable isotope probes, 2-dimethylaminoethylamine (DMED) and d4-2-dimethylaminoethylamine (d4-DMED), were utilized to facilely label eicosanoids. The heavy labeled eicosanoid standards were prepared and used as internal standards for quantification to minimize the matrix and ion suppression effects in mass spectrometry analysis. In addition, the detection sensitivities of DMED labeled eicosanoids improved by 3-104 folds in standard solution and 5-138 folds in serum matrix compared with unlabeled analytes. Moreover, a good separation of eicosanoids isomers was achieved upon DMED labeling. The established method provided substantial sensitivity (limit of quantification at sub-picogram), high specificity, and broad linear dynamics range (3 orders of magnitude). We further quantified cytochrome P450 metabolites of AA in rat liver, heart, brain tissues and human serum using the developed method. The results showed that 19 eicosanoids could be distinctly detected and the contents of 11-, 15-, 16-, 20-HETE, 5,6-EET, and 14,15-EET in type 2 diabetes mellitus patients and 5-, 11-, 12-, 15-, 16-, 20-HETE, 8,9-EET, and 5,6-DHET in myeloid leukemia patients had significant changes

  18. AD6 (8-monochloro-3-beta-diethylamino-ethyl-4-methyl-7-ethoxycarbonyl-meth oxy coumarin) inhibits the release of arachidonic acid in human platelets stimulated by thrombin

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    Porcellati, S.; Costantini, V.; Prosdocimi, M.; Pistolesi, R.; Porrovecchio, P.; Nenci, G.G.; Goracci, G.


    The coumarin derivative AD6 is known to inhibit platelet aggregation and release and it possesses vasodilatory properties on coronary arteries of laboratory animals. Furthermore, the inhibition of the production of TxB2 from endogenous substrates after stimulation of human platelets with collagen has been demonstrated. The present report demonstrates that AD6 inhibits the production of labeled arachidonic acid and diglycerides from phospholipids of platelets stimulated with thrombin. This effect is dose-dependent and is already evident at a concentration of the drug (25 microM) which is unable to prevent the aggregation. Apparently, AD6 inhibits the release of arachidonic acid from phosphatidylinositol and choline phosphoglycerides which are the main sources of the substrate for the synthesis of prostaglandins and thromboxanes.

  19. 内皮源性缩血管因子花生四烯酸代谢物的作用多样性%Diversity of endothelium-derived vasocontracting factors--arachidonic acid metabolites

    Institute of Scientific and Technical Information of China (English)

    KURAHASHI Kazuyoshi; NISHIHASHI Tsuyoshi; TRANDAFIR Cristina Corina; WANG Ai-Min; MURAKAMI Shizuka; JI Xu


    Vascular endothelium releases vasocontracting and/or vasorelaxing substances. Here, we report the diversity of endothelium-derived vasocontracting factors (EDCFs), arachidonic acid metabolites, and discuss the pathophysiological significance. In the canine basilar artery and the rabbit intrapulmonary artery, acetylcholine-induced contractions (Ach-induced EDC) are due to endothelial thromboxane A2 (TXA2) (TXA2-type). The Ach-induced EDC in the rabbit coronary artery is due to endothelial leukotrienes (LTs) (LTs-type). In addition, in the rat coronary artery, nicotine and noradrenaline (Nad)-induced EDCs are due to endothelial COX-metabolites (COX metabolite-type). These arachidonic acid metabolites derived from endothelium (activation by vasoactive substances including Ach, Nad and nicotine) cause a contraction of vascular smooth muscle cells and may disturb the local circulation. These EDCFs (TXA2, LTs and COX-metabolites) may be involved in the pathophysiology of cardiovascular immuno-inflammatory diseases.

  20. Dose-dependent changes in neuroinflammatory and arachidonic acid cascade markers with synaptic marker loss in rat lipopolysaccharide infusion model of neuroinflammation

    Directory of Open Access Journals (Sweden)

    Kellom Matthew


    Full Text Available Abstract Background Neuroinflammation, caused by six days of intracerebroventricular infusion of bacterial lipopolysaccharide (LPS, stimulates rat brain arachidonic acid (AA metabolism. The molecular changes associated with increased AA metabolism are not clear. We examined effects of a six-day infusion of a low-dose (0.5 ng/h and a high-dose (250 ng/h of LPS on neuroinflammatory, AA cascade, and pre- and post-synaptic markers in rat brain. We used artificial cerebrospinal fluid-infused brains as controls. Results Infusion of low- or high-dose LPS increased brain protein levels of TNFα, and iNOS, without significantly changing GFAP. High-dose LPS infusion upregulated brain protein and mRNA levels of AA cascade markers (cytosolic cPLA2-IVA, secretory sPLA2-V, cyclooxygenase-2 and 5-lipoxygenase, and of transcription factor NF-κB p50 DNA binding activity. Both LPS doses increased cPLA2 and p38 mitogen-activated protein kinase levels, while reducing protein levels of the pre-synaptic marker, synaptophysin. Post-synaptic markers drebrin and PSD95 protein levels were decreased with high- but not low-dose LPS. Conclusions Chronic LPS infusion has differential effects, depending on dose, on inflammatory, AA and synaptic markers in rat brain. Neuroinflammation associated with upregulated brain AA metabolism can lead to synaptic dysfunction.

  1. Chronic dietary n-6 PUFA deprivation leads to conservation of arachidonic acid and more rapid loss of DHA in rat brain phospholipids. (United States)

    Lin, Lauren E; Chen, Chuck T; Hildebrand, Kayla D; Liu, Zhen; Hopperton, Kathryn E; Bazinet, Richard P


    To determine how the level of dietary n-6 PUFA affects the rate of loss of arachidonic acid (ARA) and DHA in brain phospholipids, male rats were fed either a deprived or adequate n-6 PUFA diet for 15 weeks postweaning, and then subjected to an intracerebroventricular infusion of (3)H-ARA or (3)H-DHA. Brains were collected at fixed times over 128 days to determine half-lives and the rates of loss from brain phospholipids (J out). Compared with the adequate n-6 PUFA rats, the deprived n-6-PUFA rats had a 15% lower concentration of ARA and an 18% higher concentration of DHA in their brain total phospholipids. Loss half-lives of ARA in brain total phospholipids and fractions (except phosphatidylserine) were longer in the deprived n-6 PUFA rats, whereas the J out was decreased. In the deprived versus adequate n-6 PUFA rats, the J out of DHA was higher. In conclusion, chronic n-6 PUFA deprivation decreases the rate of loss of ARA and increases the rate of loss of DHA in brain phospholipids. Thus, a low n-6 PUFA diet can be used to target brain ARA and DHA metabolism.

  2. Nrf2 is crucial for the down-regulation of Cyp7a1 induced by arachidonic acid in Hepg2 cells. (United States)

    Zhang, Jin-Ming; Wang, Xing-He; Hao, Li-Hong; Wang, He; Zhang, Xiu-Ying; Muhammad, Ishfaq; Qi, Yue; Li, Guang-Liang; Sun, Xiao-Qi


    In former research, cyp7a1 expression was decreased but Nrf2 transcription and hepatic arachidonic acid (AA) concentration were increased in high-fat diet fed mice. This study aims to investigate the influence of AA in CYP7A1 expression and the role of Nrf2 in regulating CYP7A1 in the process. HepG2 cells were administered with different concentrations of AA. Nrf2 and CYP7A1 expressions were analyzed by real-time PCR and western blot. Nrf2 silenced and over-expressed cell models were constructed by Nrf2 siRNA and eukaryotic expression vector transient transfections and were used to investigate the role of Nrf2 in regulating CYP7A1 following AA administration. The results showed that Nrf2 was increased dose-dependently but CYP7A1 was decreased dose-dependently in cells treated with increasing concentrations of AA. The expression of CYP7A1 was increased by Nrf2 silence and was decreased by Nrf2 over-expression in HepG2 cells treated with different concentrations of AA. In conclusion, Nrf2 plays a significant role in the down-regulation of CYP7A1 induced by AA in HepG2 cells.

  3. Determination of arachidonic acid by on-line solid-phase extraction HPLC with UV detection for screening of cytosolic phospholipase A2α inhibitors. (United States)

    Hanekamp, Walburga; Lehr, Matthias


    An on-line solid-phase extraction (SPE)-liquid chromatographic method with ultraviolet detection at 200nm for screening of inhibitors of cytosolic phospholipase A(2)α (cPLA(2)α) was developed and validated. cPLA(2)α was isolated from porcine platelets. Enzyme activity was determined by measuring the release of arachidonic acid from a phospholipid substrate using automated on-line sample clean up on a trap column followed by isocratic back-flush elution on a RP18 analytical column. While the use of a conventional RP18 column for trapping the analyte led to peak broadening only after a few runs due to pollution of the column by binding of components present in the enzyme preparation, the application of a turbulent flow column (TurboFlow Cyclone™) resulted in sharp peaks even after a plurality of injections. Interestingly, for sample introduction a turbulent flow of the mobile phase produced by high flow rates was not necessary to maintain good peak shapes. The same result could also be achieved applying low flow rates (0.5 mL/min). Several known cPLA(2)α inhibitors were used to validate the test system.

  4. Arachidonic acid affects biofilm formation and PGE2 level in Candida albicans and non-albicans species in presence of subinhibitory concentration of fluconazole and terbinafine. (United States)

    Mishra, Nripendra Nath; Ali, Shakir; Shukla, Praveen K


    Candida albicans utilizes arachidonic acid (AA) released during the course of infection (Candidiasis) from phospholipids of infected host cell membranes and synthesizes extracellular prostaglandin(s) which play an important role in hyphae formation and host cell damage. C. albicans biofilms secrete significantly more prostaglandin(s) and evidence suggests that Candida biofilms have dramatically reduced susceptibility to majority of antifungal drugs. AA influences the saturation level of lipids and fluidity of yeast cell membranes. Therefore the aim of this study was to evaluate the effect of AA alone or in combination with antifungal agents on biofilm formation and production of prostaglandin (PGE2) in C. albicans, C. parapsilosis, C. glabrata, C. tropicalis, and C. albicans amphotericin B resistant strain (AmBR). Maximum biofilm formation was found to be in the case of C. albicans compared to C. non-albicans species. However, among the non-albicans species C. tropicalis exhibited highest biofilm formation. Treatment with AA in combination with subinhibitory concentrations of fluconazole and terbinafine separately exhibited significant (p<0.05) reduction in biofilm formation against C. glabrata, C. parapsilosis, C. tropicalis and AmBR as compared to their individual effect. Further, these two antifungal agents in combination with AA caused an increase in production of prostaglandin from fungal cell itself which was significant (p<0.05) in case of all the strains tested.

  5. Prostaglandin E2 and the protein kinase A pathway mediate arachidonic acid induction of c-fos in human prostate cancer cells (United States)

    Chen, Y.; Hughes-Fulford, M.


    Arachidonic acid (AA) is the precursor for prostaglandin E2 (PGE2) synthesis and increases growth of prostate cancer cells. To further elucidate the mechanisms involved in AA-induced prostate cell growth, induction of c-fos expression by AA was investigated in a human prostate cancer cell line, PC-3. c-fos mRNA was induced shortly after addition of AA, along with a remarkable increase in PGE2 production. c-fos expression and PGE2 production induced by AA was blocked by a cyclo-oxygenase inhibitor, flurbiprofen, suggesting that PGE2 mediated c-fos induction. Protein kinase A (PKA) inhibitor H-89 abolished induction of c-fos expression by AA, and partially inhibited PGE2 production. Protein kinase C (PKC) inhibitor GF109203X had no significant effect on c-fos expression or PGE2 production. Expression of prostaglandin (EP) receptors, which mediate signal transduction from PGE2 to the cells, was examined by reverse transcription polymerase chain reaction in several human prostate cell lines. EP4 and EP2, which are coupled to the PKA signalling pathway, were expressed in all cells tested. Expression of EP1, which activates the PKC pathway, was not detected. The current study showed that induction of the immediate early gene c-fos by AA is mediated by PGE2, which activates the PKA pathway via the EP2/4 receptor in the PC-3 cells.

  6. Identification of a cyclooxygenase gene from the red alga Gracilaria vermiculophylla and bioconversion of arachidonic acid to PGF(2α) in engineered Escherichia coli. (United States)

    Kanamoto, Hirosuke; Takemura, Miho; Ohyama, Kanji


    Prostaglandins (PGs) are important local messenger molecules in many tissues and organs of animals including human. For applications in medicine and animal care, PGs are mostly purified from animal tissues or chemically synthesized. To generate a clean, reliable, and inexpensive source for PGs, we have now engineered expression of a suitable cyclooxygenase gene in Escherichia coli and achieved production levels of up to 2.7 mg l(-1) PGF(2α). The cyclooxygenase gene cloned from the red alga Gracilaria vermiculophylla appears to be fully functional without any eukaryotic modifications in E. coli. A crude extract of the recombinant E. coli cells is able to convert in vitro the substrate arachidonic acid (AA) to PGF(2α). Furthermore, these E. coli cells produced PGF(2α) in a medium supplemented with AA and secreted the PGF(2α) product. To our knowledge, this is the first report of the functional expression of a cyclooxygenase gene and concomitant production of PGF(2α) in E. coli. The successful microbial synthesis of PGs with reliable yields promises a novel pharmaceutical tool to produce PGF(2α) at significantly reduced prices and greater purity.

  7. Comparison of the effect of timegadine, levamisole, and D-penicillamine on human neutrophil metabolism of endogenous arachidonic acid and chemotaxis

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    Nielsen, O.H.; Ahnfelt-Roenne, I. Department of Pharmacology, Leo Pharmaceutical Products, Ballerup; Elmgreen, J.


    The effect of timegadine, a novel experimental antirheumatic drug, on human neutrophil (PMN) 5-lipoxygenase activity and leukotriene B/sub 4/ (LTB/sub 4/) chemotaxis was compared with that of two second-line antiinflammatory drugs, D-penicillamine and levamisole. 1-/sup 14/C-Arachidonic acid (AA) was incorporated into the purified cells until steady state conditions were obtained. After preincubation with serial dilutions of the three drugs, AA release and metabolism was stimulated with calcium ionophore A23187. The radioactive eicosanoids released were extracted and separated by thinlayer chromatography, followed by autoradiography and quantitative laser densitometry. Chemotaxi of PMNs towards LTB/sub 4/ was measured in a modified Boyden chamber. Timegardine showed dose-dependent inhibition of both the 5-lipoxygenase pathway (IC50 3.4 x 10/sup -5/ M), and of chemotaxis (IC50 3 x 10/sup -4/ M). Inhibition of the release of AA from phospholipids, however, occurred only at therapeutically irrelevant doses (millimolar concentrations). Levamisole and D-penicillamine did not inhibit any of the cell functions investigated. Inhibition of both neutrophil motility and cellular synthesis of pro-inflammatory eicosanoids, may thus contribute to the clinical effects of timegadine in rheumatoid arthritis.

  8. Arachidonic acid alters tomato HMG expression and fruit growth and induces 3-hydroxy-3-methylglutaryl coenzyme A reductase-independent lycopene accumulation

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez-Concepcion, M.; Gruissem, W. [Univ. of California, Berkeley, CA (United States). Dept. of Plant and Microbial Biology


    Regulation of isoprenoid end-product synthesis required for normal growth and development in plants is not well understood. To investigate the extent to which specific genes for the enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) are involved in end-product regulation, the authors manipulated expression of the HMG1 and HMG2 genes in tomato (Lycopersicon esculentum) fruit using arachidonic acid (AA). In developing young fruit AA blocked fruit growth, inhibited HMG1, and activated HMG2 expression. These results are consistent with other reports indicating that HMG1 expression is closely correlated with growth processes requiring phytosterol production. In mature-green fruit AA strongly induced the expression of HMG2, PSY1 (the gene for phytoene synthase), and lycopene accumulation before the normal onset of carotenoid synthesis and ripening. The induction of lycopene synthesis was not blocked by inhibition of HMGR activity using mevinolin, suggesting that cytoplasmic HMGR is not required for carotenoid synthesis. Their results are consistent with the function of an alternative plastid isoprenoid pathway (the Rohmer pathway) that appears to direct the production of carotenoids during tomato fruit ripening.

  9. The role of the arachidonic acid cascade in the species-specific X-ray-induced inflammation of the rabbit eye

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    Bito, L.Z.; Klein, E.M.


    To identify the mediator(s) of the apparently species-specific X-ray-induced inflammation of the rabbit eye, inhibitors of the synthesis and/or release of known or putative mediators of ocular inflammation were administered prior to irradiation. The X-ray-induced ocular inflammation, particularly the rise in intraocular pressure, was found to be inhibited by intravenous pretreatment of rabbits with flurbiprofen, indomethacin, or imidazole (1, 10, and 100 mg/kg i.v., respectively), or by combined intravitreal and topical administration of flurbiprofen. Systemic, intravitreal, and/or topical pretreatment with prednisolone or disodium cromoglycate or the retrobulbar injection of ethyl alcohol or capsaicin failed to block the inflammatory response, whereas vitamin E apparently exerted some protective effect. These findings show that the X-ray-induced inflammation of the rabbit eye is mediated, at least in part, by prostaglandins (PGs) and/or related autacoids. In addition, these results suggest that the unique sensitivity of the rabbit eye to X-ray-induced inflammation is due either to the presence in this species of a unique or uniquely effective triggering mechanism for the release of PG precursors or to the greater sensitivity of this species to the ocular inflammatory effects of PGs. Thus the rabbit eye may provide a unique model for studying some aspects of arachidonic acid release or ocular PG effects, but extreme caution must be exercised in generalizing such findings to other species.

  10. Inhibition of protein kinase B by Palmitate in the insulin signaling of HepG2 cells and the preventive effect of Arachidonic acid on insulin resistance

    Institute of Scientific and Technical Information of China (English)

    XIA Yanzhi; WAN Xuedong; DUAN Qiuhong; HE Shansu; WANG Ximing


    Elevated plasma levels of free fatty acids(FFAs)may contribute to insulin resistance (IR)that is characteristic of type 2 diabetes mellitus.In this study,we investigated the effects of two fatty acids,palmitate(PA)and arachidonic acid (AA)on glycogenesis under insulin signaling in HepG2cells,a transformed hepatic carcinoma cell line.In the presence of 200 μmol of palmitate,insulin(10-7 mol/L)stimulation of glycogenesis was inhibited,as evidenced by increased glucose in the medium and decreased intracellular glycogen.Wortmannin(WM),a specific inhibitor of PI3K,dramatically decreased the amount of intracellular glycogen in cells without PA incubation.However,glycogen in PA treated cells was not significantly changed by WM,indicating that PA may also act on PI3K.Interestingly,AA restored the effects of WM inhibition on glycogenesis in PA cells.Western blot analysis demonstrated that PA in the absence of WM increased phosphorylated glycogen synthase(inactive form of GS)and decreased phosphorylated protein kinase B(active form of PKB),causing a reduction of intracellular glycogen.AA,however,reversed the effects of PA on GS and PKB.Furthermore,inhibition of protein kinase C(PKC)by a specific inhibitor chelerythrine chloride (CC)abolished the inhibitory efrect of PA on glycogen synthesis by decreasing phosphorylated GS and increasing phosphorylated PKB.However,the effect of CC in the presence of PA disappeared when AA was also present.Our results suggest that there is a disruption of the insulin signaling pathway between PKB and GS when the cells were exposed to PA,contributing to IR.PA may also interrupt the PKC signaling pathway.In contrast,AA could rescue glycogenesis impaired by PA.

  11. Consumption of Red Meat, but Not Cooking Oils High in Polyunsaturated Fat, Is Associated with Higher Arachidonic Acid Status in Singapore Chinese Adults (United States)

    Seah, Jowy Yi Hoong; Gay, Gibson Ming Wei; Su, Jin; Tai, E-Shyong; Yuan, Jian-Min; Koh, Woon-Puay; Ong, Choon Nam; van Dam, Rob M.


    High arachidonic acid (AA; 20:4n-6) status may have adverse effects on inflammation and risk of cardiovascular diseases. Concerns about high intake of n-6 polyunsaturated fatty acids (PUFAs) are based on the premise that endogenous conversion from linoleic acid (LA; 18:2n-6) is an important source of AA, but few population-based studies have investigated dietary determinants of AA status. In this study, we examined habitual food consumption in relation to plasma concentrations of AA and other PUFAs in population-based studies. We used cross-sectional data from 269 healthy, ethnic Chinese participants (25–80 years old) with contrasting intakes of fish and red meat from the Singapore Prospective Study Program and 769 healthy participants (44–74 years old) from the Singapore Chinese Health Study as a validation set. Multivariable linear regression was used to examine PUFA intake (% energy) and food sources of PUFA (fish, red meat, poultry, soy and cooking oils) in relation to plasma PUFAs (AA, LA, dihomo-gamma-linolenic acid (DGLA; 20:3n-6), alpha-linolenic acid (ALA; 18:3n-3), eicosapentaenoic acid (EPA; 20:5n-3), and docosahexaenoic acid (DHA; 22:6n-3)) concentrations. Higher intake of red meat was associated with higher plasma AA concentrations. High intake of PUFA or PUFA-rich oils was associated with higher plasma ALA but not with plasma AA. Higher intakes of soy were associated with higher ALA and fish with higher DHA and EPA concentrations. These associations were statistically significant (p < 0.05) in both studies. Red meat consumption, but not PUFA or PUFA-rich cooking oil, was associated with circulating AA suggesting that intake of pre-formed AA rather than LA is an important determinant of AA status. A diet high in fish, soy products and polyunsaturated cooking oil, and low in red meat may be associated with an optimal plasma profile of PUFA in this Chinese population. PMID:28146136

  12. Consumption of Red Meat, but Not Cooking Oils High in Polyunsaturated Fat, Is Associated with Higher Arachidonic Acid Status in Singapore Chinese Adults

    Directory of Open Access Journals (Sweden)

    Jowy Yi Hoong Seah


    Full Text Available High arachidonic acid (AA; 20:4 n − 6 status may have adverse effects on inflammation and risk of cardiovascular diseases. Concerns about high intake of n − 6 polyunsaturated fatty acids (PUFAs are based on the premise that endogenous conversion from linoleic acid (LA; 18:2 n − 6 is an important source of AA, but few population-based studies have investigated dietary determinants of AA status. In this study, we examined habitual food consumption in relation to plasma concentrations of AA and other PUFAs in population-based studies. We used cross-sectional data from 269 healthy, ethnic Chinese participants (25–80 years old with contrasting intakes of fish and red meat from the Singapore Prospective Study Program and 769 healthy participants (44–74 years old from the Singapore Chinese Health Study as a validation set. Multivariable linear regression was used to examine PUFA intake (% energy and food sources of PUFA (fish, red meat, poultry, soy and cooking oils in relation to plasma PUFAs (AA, LA, dihomo-gamma-linolenic acid (DGLA; 20:3 n − 6, alpha-linolenic acid (ALA; 18:3 n − 3, eicosapentaenoic acid (EPA; 20:5 n − 3, and docosahexaenoic acid (DHA; 22:6 n − 3 concentrations. Higher intake of red meat was associated with higher plasma AA concentrations. High intake of PUFA or PUFA-rich oils was associated with higher plasma ALA but not with plasma AA. Higher intakes of soy were associated with higher ALA and fish with higher DHA and EPA concentrations. These associations were statistically significant (p < 0.05 in both studies. Red meat consumption, but not PUFA or PUFA-rich cooking oil, was associated with circulating AA suggesting that intake of pre-formed AA rather than LA is an important determinant of AA status. A diet high in fish, soy products and polyunsaturated cooking oil, and low in red meat may be associated with an optimal plasma profile of PUFA in this Chinese population.

  13. Arachidonic acid metabolism in TNS-induced chronic and immunologic enteritis in rats, and the effect of 5-ASA

    NARCIS (Netherlands)

    F.J. Zijlstra (Freek); A.P.J. van Dijk (Arie); N. Selve (N.); J.H.P. Wilson (Paul)


    textabstractInflammation of the rat distal intestine was induced by intradermal sensitization and subsequent multiple intrajejunal challenge with the hapten 2,4,6-trinitrobenzenesulphonic acid (TNBS) via an implanted catheter. The time course of the inflammatory reaction was followed by determinatio

  14. Arachidonic acid enhances TPA-induced differentiation in human leukemia HL-60 cells via reactive oxygen species-dependent ERK activation. (United States)

    Chien, Chih-Chiang; Wu, Ming-Shun; Shen, Shing-Chuan; Yang, Liang-Yo; Wu, Wen-Shin; Chen, Yen-Chou


    The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), is a potent stimulator of differentiation in human leukemia cells; however, the effects of arachidonic acid (AA) on TPA-induced differentiation are still unclear. In the present study, we investigated the contribution of AA to TPA-induced differentiation of human leukemia HL-60 cells. We found that treatment of HL-60 cells with TPA resulted in increases in cell attachment and nitroblue tetrazolium (NBT)-positive cells, which were significantly enhanced by the addition of AA. Stimulation of TPA-induced intracellular reactive oxygen species (ROS) production by AA was detected in HL-60 cells via a DCHF-DA analysis, and the addition of the antioxidant, N-acetyl-cysteine (NAC), was able to reduce TPA+AA-induced differentiation in accordance with suppression of intracellular peroxide elevation by TPA+AA. Furthermore, activation of extracellular-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) by TPA+AA was identified in HL-60 cells, and the ERK inhibitor, PD98059, but not the JNK inhibitor, SP600125, inhibited TPA+AA-induced NBT-positive cells. Suppression of TPA+AA-induced ERK protein phosphorylation by PD98059 and NAC was detected, and AA enhanced ERK protein phosphorylation by TPA was in HL-60 cells. AA clearly increased TPA-induced HL-60 cell differentiation, as evidenced by a marked increase in CD11b expression, which was inhibited by NAC and PD98059 addition. Eicosapentaenoic acid (EPA) as well as AA showed increased intracellular peroxide production and differentiation of HL-60 cells elicited by TPA. Evidence of AA potentiation of differentiation by TPA in human leukemia cells HL-60 via activation of ROS-dependent ERK protein phosphorylation was first demonstrated herein.

  15. Antagonizing arachidonic acid-derived eicosanoids reduces inflammatory Th17 and Th1 cell-mediated inflammation and colitis severity. (United States)

    Monk, Jennifer M; Turk, Harmony F; Fan, Yang-Yi; Callaway, Evelyn; Weeks, Brad; Yang, Peiying; McMurray, David N; Chapkin, Robert S


    During colitis, activation of two inflammatory T cell subsets, Th17 and Th1 cells, promotes ongoing intestinal inflammatory responses. n-6 polyunsaturated fatty acid- (PUFA-) derived eicosanoids, such as prostaglandin E2 (PGE2), promote Th17 cell-mediated inflammation, while n-3 PUFA antagonize both Th17 and Th1 cells and suppress PGE2 levels. We utilized two genetic mouse models, which differentially antagonize PGE2 levels, to examine the effect on Th17 cells and disease outcomes in trinitrobenzene sulfonic acid- (TNBS-) induced colitis. Fat-1 mice contain the ω3 desaturase gene from C. elegans and synthesize n-3 PUFA de novo, thereby reducing the biosynthesis of n-6 PUFA-derived eicosanoids. In contrast, Fads1 Null mice contain a disrupted Δ5 desaturase gene and produce lower levels of n-6 PUFA-derived eicosanoids. Compared to Wt littermates, Fat-1 and Fads1 Null mice exhibited a similar colitic phenotype characterized by reduced colonic mucosal inflammatory eicosanoid levels and mRNA expression of Th17 cell markers (IL-17A, RORγτ, and IL-23), decreased percentages of Th17 cells and, improved colon injury scores (P ≤ 0.05). Thus, during colitis, similar outcomes were obtained in two genetically distinct models, both of which antagonize PGE2 levels via different mechanisms. Our data highlight the critical impact of n-6 PUFA-derived eicosanoids in the promotion of Th17 cell-mediated colonic inflammation.

  16. Antagonizing Arachidonic Acid-Derived Eicosanoids Reduces Inflammatory Th17 and Th1 Cell-Mediated Inflammation and Colitis Severity

    Directory of Open Access Journals (Sweden)

    Jennifer M. Monk


    Full Text Available During colitis, activation of two inflammatory T cell subsets, Th17 and Th1 cells, promotes ongoing intestinal inflammatory responses. n-6 polyunsaturated fatty acid- (PUFA- derived eicosanoids, such as prostaglandin E2 (PGE2, promote Th17 cell-mediated inflammation, while n-3 PUFA antagonize both Th17 and Th1 cells and suppress PGE2 levels. We utilized two genetic mouse models, which differentially antagonize PGE2 levels, to examine the effect on Th17 cells and disease outcomes in trinitrobenzene sulfonic acid- (TNBS- induced colitis. Fat-1 mice contain the ω3 desaturase gene from C. elegans and synthesize n-3 PUFA de novo, thereby reducing the biosynthesis of n-6 PUFA-derived eicosanoids. In contrast, Fads1 Null mice contain a disrupted Δ5 desaturase gene and produce lower levels of n-6 PUFA-derived eicosanoids. Compared to Wt littermates, Fat-1 and Fads1 Null mice exhibited a similar colitic phenotype characterized by reduced colonic mucosal inflammatory eicosanoid levels and mRNA expression of Th17 cell markers (IL-17A, RORγτ, and IL-23, decreased percentages of Th17 cells and, improved colon injury scores (P≤0.05. Thus, during colitis, similar outcomes were obtained in two genetically distinct models, both of which antagonize PGE2 levels via different mechanisms. Our data highlight the critical impact of n-6 PUFA-derived eicosanoids in the promotion of Th17 cell-mediated colonic inflammation.

  17. Effects of arachidonic acid supplementation in maturation diet on female reproductive performance and larval quality of giant river prawn (Macrobrachium rosenbergii) (United States)

    Pratoomyot, Jarunan; Siranonthana, Nisa; Senanan, Wansuk


    The giant river prawn (Macrobrachium rosenbergii) is one of the most farmed freshwater crustaceans in the world. Its global production has been stalling in the past decade due to the inconsistent quality of broodstock and hatchery-produced seeds. A better understanding of the role of nutrition in maturation diets will help overcome some of the production challenges. Arachidonic acid (20:4 n-6, ARA) is a fatty acid precursor of signaling molecules important for crustacean reproduction, prostaglandins E and F of the series II (PGE2 and PGF2α), and is often lacking in maturation diets of shrimp and prawns. We examined the effects of ARA in a combination of different fish oil (FO) and soybean oil (SO) blends on females’ reproductive performance and larval quality. Adult females (15.22 ± 0.13 g and 11.12 ± 0.09 cm) were fed six isonitrogenous and isolipidic diets containing one of two different base compositions (A or B), supplemented with one of three levels of Mortierella alpine-derived ARA (containing 40% active ARA): 0, 1 or 2% by ingredient weight. The two base diets differed in the percentages of (FO and SO with diet A containing 2% SO and 2% FO and diet B containing 2.5% SO and 1.5% FO, resulting in differences in proportional contents of dietary linoleic acid (18:2n-6, LOA) and docosahexaenoic acid (22:6n-3, DHA)). After the eight-week experiment, prawns fed diet B with 1 and 2% ARA supplement (B1 and B2) exhibited the highest gonadosomatic index (GSI), hepatosomatic index (HSI), egg clutch weight, fecundity, hatching rate, number of larvae, and reproductive effort compared to those fed other diets (p ≤ 0.05). Larvae from these two dietary treatments also had higher tolerance to low salinity (2 ppt). The maturation period was not significantly different among most treatments (p ≥ 0.05). ARA supplementation, regardless of the base diet, significantly improved GSI, HSI, egg clutch weight and fecundity. However, the diets with an enhanced ARA and LOA

  18. Role for calcium signaling and arachidonic acid metabolites in the activity-dependent increase of AHP amplitude in leech T sensory neurons. (United States)

    Scuri, Rossana; Mozzachiodi, Riccardo; Brunelli, Marcello


    Previous studies have revealed a new form of activity-dependent modulation of the afterhyperpolarization (AHP) in tactile (T) neurons of the leech Hirudo medicinalis. The firing of T cells is characterized by an AHP, which is mainly due to the activity of the Na+/K+ ATPase. Low-frequency repetitive stimulation of T neurons leads to a robust increment of the AHP amplitude, which is correlated with a synaptic depression between T neuron and follower cells. In the present study, we explored the molecular cascades underlying the AHP increase. We tested the hypothesis that this activity-dependent phenomenon was triggered by calcium influx during neural activity by applying blockers of voltage-dependent Ca2+ channels. We report that AHP increase requires calcium influx that, in turn, induces release of calcium from intracellular stores so sustaining the enhancement of AHP. An elevation of the intracellular calcium can activate the cytosolic isoforms of the phosholipase A2 (PLA2). Therefore we analyzed the role of PLA2 in the increase of the AHP, and we provide evidence that not only PLA2 but also the recruitment of arachidonic acid metabolites generated by the 5-lipoxygenase pathway are necessary for the induction of AHP increase. These data indicate that a sophisticated cascade of intracellular signals links the repetitive discharge of T neurons to the activation of molecular pathways, which finally may alter the activity of critical enzymes such as the Na+/K+ ATPase, that sustains the generation of the AHP and its increase during repetitive stimulation. These results also suggest the potential importance of the poorly studied 5-lipoxygenase pathway in forms of neuronal plasticity.

  19. Effects of fluticasone propionate on arachidonic acid metabolites in BAL-fluid and methacholine dose-response curves in non-smoking atopic asthmatics

    Directory of Open Access Journals (Sweden)

    S. E. Overbeek


    Full Text Available Hyperresponsiveness of the airways to nonspecific stimuli is a characteristic feature of asthma. Airway responsiveness is usually characterized in terms of the position and shape of the dose–response curve to methacholine (MDR. In the study we have investigated the influence of fluticasone propionate (FP, a topically active glucocorticoid, on arachidonic acid (AA metabolites in broncho-alveolar lavage (BAL fluid (i.e. TxB2, PGE2, PGD2, 6kPGF1α and LTC4 on the one hand and MDR curves on the other hand. The effect of FP was studied in a randomized, double-blind, placebo-controlled design in 33 stable nonsmoking asthmatics; 16 patients received FP (500 μg b.i.d. whereas 17 patients were treated with placebo. We found that the forced expiratory volume in 1s (FEV1 % predicted increased, the log2PC20 methacholine increased and the plateau value (% fall in FEV1 decreased after a 12 week treatment period. No changes in AA-metabolites could be determined after treatment except for PGD2 which decreased nearly significantly (p = 0.058 within the FP treated group, whereas the change of PGD2 differed significantly (p = 0.05 in the FP treated group from placebo. The levels of the other AA metabolites (i.e. TxB2, PGE2, 6kPGF1α and LTC4 remained unchanged after treatment and were not significantly different from the placebo group. Our results support the hypothesis that although FP strongly influences the position, the shape and also the maximum response plateau of the MDR curve, this effect is not mainly achieved by influence on the level of AA metabolites. Other pro-inflammatory factors may be of more importance for the shape of the MDR curve. It is suggested that these pro-inflammatory factors are downregulated by FP.

  20. Molecular cloning and functional characterization of arachidonate 5-lipoxygenase (Alox5), and its expression in response to the ratio of linolenic acid to linoleic acid in diets of large yellow croaker (Larmichthys crocea). (United States)

    Wang, Tianjiao; Zuo, Rantao; Mai, Kangsen; Xu, Wei; Ai, Qinghui


    This study was conducted to clone and functionally characterize a full-length cDNA encoding arachidonate 5-lipoxygenase (Alox5) from large yellow croaker (Larmichthys crocea) and investigate its gene expression in response to graded dietary ratio of linolenic acid (ALA) to linoleic acid (LNA) (0.03, 0.06, 0.45, 0.90 and 1.51). An isolated 2372bp cDNA clone of Alox5 contained an open reading frame spanning 2025bp encoding a protein with the ability to modify arachidonate acid (AA) to 5-hydroxyeicosatetraenoic (5-HETE). In the liver, the Alox5 mRNA expression levels significantly increased to the maximum when the dietary ALA/LNA increased from 0.03 to 0.06, and then significantly decreased with dietary ALA/LNA increased to 1.51 (P<0.05). In the kidney, the expression levels of Alox5 of fish fed diets with low dietary ALA/LNA (0.03-0.06) were significantly higher than those of fish fed diets with high dietary ALA/LNA (0.45-1.51) (P<0.05). The dual-luciferase reporter assays showed that the nuclear factor kappa B (NF-κB) could act on cognate cis-acting elements in the promoter of Alox5 and increased the transcription of Alox5. Results of the present study suggested that the expression of Alox5 is higher in croakers fed high concentrations of LNA compared to those fed high concentrations of ALA, which might be regulated by NF-κB and contribute to the inflammation process by catalyzing the dioxygenation of AA.

  1. 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.


    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...... to increased dietary ARA content. However, pigmentation was not affected by inclusion levels of EPA or DHA when ARA was high. This, and no relation between DHA: EPA or ARA: EPA ratios and pigmentation and only a weak relation to ARA: DHA ratio, advocate for that it is the absolute concentration of ARA...... resulted in a lower growth rate, which suggests that visual aberrations affected prey capture. (C) 2007 Elsevier B.V. All rights reserved....

  2. The application of arachidonic acid in dairy products%花生四烯酸在乳制品中的应用

    Institute of Scientific and Technical Information of China (English)

    詹现璞; 吕银德; 赵俊芳


    花生四烯酸(AA)是一种人体必需的多不饱和脂肪酸,是人体生长因子,影响婴幼儿大脑和神经发育.AA具有改善记忆力和视力、调节血脂和血糖、降低血清胆固醇、预防心血管疾病、辅助抑制肿瘤、预防癌变、神经功能调节等作用.人体自身不能合成AA,必需从食物补充才能满足机体代谢的需要,牛乳是人体补充营养物质的载体,而AA在牛乳中几乎不存在,所以在牛乳中强化AA已显得非常必要.本文介绍了AA添加带配方奶粉中的工艺流程和操作要点;AA应用于纯牛奶中的工艺流程和操作要点;开发富含AA酸牛奶的生产工艺和操作要点;开发富含AA乳饮料的工艺流程和操作要点.研究发现,AA在酸牛奶和乳饮料中的应用将是新的发展趋势,富含AA的乳制品将会给企业带来巨大的经济效益和社会效益.%Arachidonic acid(AA)is an essential polyunsaturated fatty acids for human.It is a human growth factor,which can greatly affect infant brain and neurological development.AA can improve the memory and vision,regulate blood lipids and blood sugar,reduce cholesterol,and prevent cardiovascular disease and cancer.AA can not be synthesized by human body,it can only be obtained through food.Milk contains rich nutrients except AA,so AA fortified milk has become necessary.In this paper,the formula and process for adding AA into milk has been studied.It is found that AA in the acidophilus milk and milk drinks will be the new trend of dairy products.AA enrichment products will bring enormous economic and social benefits.

  3. Essential function of linoleic acid esterified in acylglucosylceramide and acylceramide in maintaining the epidermal water permeability barrier. Evidence from feeding studies with oleate, linoleate, arachidonate, columbinate and a-linolenate

    DEFF Research Database (Denmark)

    Hansen, Harald S.; Jensen, B.


    Essential fatty acid-deficient rats were supplemented with 300 mg per day of pure fatty acid esters: oleate (O), linoleate (L), arachidonate (A), and columbinate (C) for 10 days. During this period, the rats in groups L, A, and C all showed a decrease in their initially high trans-epidermal water...... loss, a classical essential fatty acid-deficiency symptom, to a level seen in non-deficient rats (group N). The trans-epidermal water loss in rats of group O was unaffected by the supplementation. Fatty acid composition of two epidermal sphingolipids, acylglucosylceramide and acylceramide, from...... the skin were determined. The results indicate that re-establishment of a low trans-epidermal water loss was associated with incorporation of linolenate into the two epidermal sphingolipids. Supplementation with columbinate resulted in relatively high amounts of this fatty acid in the investigated...

  4. Understanding the Mechanism of the Hydrogen Abstraction from Arachidonic Acid Catalyzed by the Human Enzyme 15-Lipoxygenase-2. A Quantum Mechanics/Molecular Mechanics Free Energy Simulation. (United States)

    Suardíaz, Reynier; Jambrina, Pablo G; Masgrau, Laura; González-Lafont, Àngels; Rosta, Edina; Lluch, José M


    Lipoxygenases (LOXs) are a family of enzymes involved in the biosynthesis of several lipid mediators. In the case of human 15-LOX, the 15-LOX-1 and 15-LOX-2 isoforms show slightly different reaction regiospecificity and substrate specificity, indicating that substrate binding and recognition may be different, a fact that could be related to their different biological role. Here, we have used long molecular dynamics simulations, QM(DFT)/MM potential energy and free energy calculations (using the newly developed DHAM method), to investigate the binding mode of the arachidonic acid (AA) substrate into 15-LOX-2 and the rate-limiting hydrogen-abstraction reaction 15-LOX-2 catalyzes. Our results strongly indicate that hydrogen abstraction from C13 in 15-LOX-2 is only consistent with the "tail-first" orientation of AA, with its carboxylate group interacting with Arg429, and that only the pro-S H13 hydrogen will be abstracted (being the pro-R H13 and H10 too far from the acceptor oxygen atom). At the B3LYP/6-31G(d) level the potential and free energy barriers for the pro-S H13 abstraction of AA by 15-LOX-2 are 18.0 and 18.6 kcal/mol, respectively. To analyze the kinetics of the hydrogen abstraction process, we determined a Markov model corresponding to the unbiased simulations along the state-discretized reaction coordinate. The calculated rates based on the second largest eigenvalue of the Markov matrices agree well with experimental measurements, and also provide the means to directly determine the pre-exponential factor for the reaction by comparing with the free energy barrier height. Our calculated pre-exponential factor is close to the value of kBT/h. On the other hand, our results suggest that the spin inversion of the complete system (including the O2 molecule) that is required to happen at some point along the full process to lead to the final hydroperoxide product, is likely to take place during the hydrogen transfer, which is a proton coupled electron transfer

  5. An arachidonic acid-enriched diet does not result in more colonic inflammation as compared with fish oil- or oleic acid-enriched diets in mice with experimental colitis. (United States)

    Ramakers, Julian D; Mensink, Ronald P; Verstege, Marleen I; te Velde, Anje A; Plat, Jogchum


    Fish oils (FO) - rich in EPA and DHA - may protect against colitis development. Moreover, inflammatory bowel disease patients have elevated colonic arachidonic acid (AA) proportions. So far, effects of dietary AA v. FO on colitis have never been examined. We therefore designed three isoenergetic diets, which were fed to mice for 6 weeks preceding and during 7 d dextran sodium sulfate colitis induction. The control diet was rich in oleic acid (OA). For the other two diets, 1.0 % (w/w) OA was exchanged for EPA+DHA (FO group) or AA. At 7 d after colitis induction, the AA group had gained weight (0.46 (sem 0.54) g), whereas the FO and OA groups had lost weight (- 0.98 (SEM 0.81) g and - 0.79 (SEM 1.05) g, respectively; P diet increased colonic AA content, but did not result in more colonic inflammation as compared with FO- and OA-enriched diets. As we only examined effects after 7 d and because the time point for evaluating effects seems to be important, the present results should be regarded as preliminary. Future studies should further elucidate differential effects of fatty acids on colitis development in time.

  6. Irradiation of human skin by short wavelength ultraviolet radiation (100--290 nm) (u.v.C): increased concentrations of arachidonic acid and prostaglandines E2 and F2alpha. (United States)

    Camp, R D; Greaves, M W; Hensby, C N; Plummer, N A; Warin, A P


    1. Human abdominal skin was irradiated with six times the minimal erythema dose of ultraviolet C (100--290 nm) radiation. Erythema appeared at 3 h, was of moderate degree by 6 h and was maximal at 12--24 h. It was reduced at 48 h and by 72 h had disappeared. 2. A suction bulla technique was used for the recovery of exudate from normal and inflamed skin at 6, 18, 24 and 48 h after irradiation. 3. Prostaglandin-like activity, estimated by bioassay, showed maximum increase at 18 h, when erythema was also maximum. PGF 2alpha, measured by both radioimmunoassay and by combined gas-liquid chromatography--gas spectrometry, followed a similar time course then fell to normal, or near normal, levels at 48 h. 4. Prostaglandin E2 and arachidonic acid concentrations, measured by gas chromatography--mass spectrometry, were maximally raised at 18--24 h. At 48 h, when some erythema was still present, though reduced, prostaglandin E2 concentrations were still raised above control values. 5. The results provide direct evidence in support of the view that the erythma following irradiation of human skin by u.v.C involves activation of arachidonic acid metabolism. However, the relationship between the erythema and increased prostaglandin activity is not fully understood.

  7. Effects of large doses of arachidonic acid added to docosahexaenoic acid on social impairment in individuals with autism spectrum disorders: a double-blind, placebo-controlled, randomized trial. (United States)

    Yui, Kunio; Koshiba, Mamiko; Nakamura, Shun; Kobayashi, Yuji


    Autism spectrum disorders are a neurodevelopmental disorders with reduced cortical functional connectivity relating to social cognition. Polyunsaturated fatty acids arachidonic acid (ARA) and docosahexaenoic acid (DHA) may have key role in brain network maturation. In particularly, ARA is important in signal transduction related to neuronal maturation. Supplementation with larger ARA doses added to DHA may therefore mitigate social impairment. In a 16-week, double-blind, randomized, placebo-controlled trial, we evaluated the efficacy of supplementation with large doses of ARA added to DHA (n = 7) or placebo (n = 6) in 13 participants (mean age, 14.6 [SD, 5.9] years). To examine underlying mechanisms underlying the effect of our supplementation regimen, we examined plasma levels of antioxidants transferrin and superoxide dismutase, which are useful markers of signal transduction. The outcome measures were the Social Responsiveness Scale and the Aberrant Behavior Checklist-Community. Repeated-measures analysis of variance revealed that our supplementation regimen significantly improved Aberrant Behavior Checklist-Community-measured social withdrawal and Social Responsiveness Scale-measured communication. Treatment effect sizes were more favorable for the treatment group compared with the placebo group (communication: treatment groups, 0.87 vs, placebo, 0.44; social withdrawal: treatment groups, 0.88, vs placebo, 0.54). There was a significant difference in the change in plasma transferrin levels and a trend toward a significant difference in the change in plasma superoxide dismutase levels between the 2 groups. This preliminary study suggests that supplementation with larger ARA doses added to DHA improves impaired social interaction in individuals with autism spectrum disorder by up-regulating signal transduction.

  8. Synthesis of (9Z, 12E-, (9E, 12Z-[1-14C]-linoleic acid, (9Z, 12Z, 15E-, (9E, 12Z, 15Z-[1-14C]-linolenic acid and (5Z, 8Z, 11Z, 14E-[1-14C]-arachidonic acid

    Directory of Open Access Journals (Sweden)

    Enard, Thierry


    Full Text Available Trans polyunsaturated fatty acids are produced in vegetable oils during heat treatment (240-250 °C.ln order to study the metabolic pathway of 9c, 12t and 9t, 12c linoleic acid and 9c, 12c, 15t and 9t, 12c, 15c linolenic acid, these products were prepared labelled with carbon 14 in the carboxylic position. 5c, 8c, 11c, 14t-Arachidonic acid was also labelled on the carboxylic position with carbon 14 in order to study its physiological effects. To introduce the labelling (E-bromo precursors with a 17 carbons chain or a 19 carbon chain were needed. The different syntheses were done by elongation steps and creation of cis double bonds via highly stereospecific Wittig reactions. The radioactive carbon atom was introduced from [14C]-potassium cyanide. The final radioactive fatty acids had a specific activity greater than 50 mCi/mmol and a radioactive purity better than 99 % for linoleic and linolenic and better than 98.6 % for arachidonic acid.

  9. Recent advances on the correlation between 5-LOX pathway of arachidonic acid and periodontitis%5-LOX代谢途径与牙周炎相关性的研究进展

    Institute of Scientific and Technical Information of China (English)



    The metabolism of arachidonic acid plays a signiifcant role in the pathological process of inlfammatory bone destruction disease. The main pathomechanism is osteoclast formation and activation. In recent years, evidence suggests that the level of LTB4 metabolized by LOX enzymatic pathway is elevated in gingival crevicular fluid of patients with periodontitis compared with periodontal health. Giving inhibitor of 5-LOX to the inlfammation model showed that the number of osteoclast and the degree of bone destruction are al below when compared with normal control. Therefore, discuss arachidonic acid metabolized by 5-LOX enzymatic pathway how to influence as wel as mechanism on periodontitis wil be conducive to expound pathogenesis of periodontitis. It proposes a new idea for the prevention and treatment of periodontitis. In this article the relationship between 5-LOX pathway of arachidonic acid and periodontitis will be reviewed.%花生四烯酸的代谢产物在炎症性骨破坏疾病的病理过程中发挥着重的作用,其主病理机制为破骨细胞的形成和活化,近年来发现花生四烯酸经脂氧酶(1ipoxygenase,LOX)途径代谢的产物LTB4在牙周炎患者龈沟液中的含量高于正常者,给予5-LOX抑制剂的炎症模型中破骨细胞的数量和骨破坏的程度均低于对照组,因而探讨花生四烯酸经5-LOX途径代谢对牙周炎的影响及其机制将有利于进一步阐明牙周炎的发病机理,为牙周炎的防治提出新的思路,本文就有关花生四烯酸脂氧酶代谢途径与牙周炎关系的研究做一综述.

  10. Effects of arachidonic acid on L-type calcium channel and its mechanism of antiarrhythmia%花生四烯酸对L-型钙通道的作用及其抗心律失常机制

    Institute of Scientific and Technical Information of China (English)

    刘承云; 陈桂青; 耿小晶; 陈心; 万晶晶


    目的 研究花生四烯酸(arachidonic acid,AA)对家兔单个心室肌细胞L-广型钙通道的作用及其抗心律失常作用的机制.方法 采用酶解法分离得到家兔单个心室肌细胞,全细胞膜片钳技术记录单个心室肌细胞L-型钙电流(L-type calcium current,Ica-L),用累积给药的方法在灌流液中加入不同浓度的AA,观察给药前后L-型钙电流的变化,统计学方法采用单因素方差分析.结果 不同浓度的从均能明显抑制心室肌细胞,Ica-L.3 μmol/L,μmol/L,20,μmol/L的AA使Ica-L峰电流密度从(10.79±0.93)pA/pF分别减少剑(8.99 ±0.43)pA/pF、(7.60 ±0.35)pA/pF和(5.60±0.30)pA/pF(n=7,P<0.05),经冲洗后Ica-L可部分恢复,并且AA可使Ica-L的I-V关系曲线上移,其形状和峰值电压保持不变;20 μmol/L的AA使Ica-L失活曲线左移,失活后恢复时间明显延长,但对激活曲线无明显影响.结论 花生四烯酸可通过加快L-型钙通道失活,延长其失活后的恢复过程而减少细胞外钙离子的内流,延长有效不应期,从而发挥抗心律失常作用.%Objective To study the influence of arachidonic acid (AA) on L-type calcium channel in rabbits sin-gle cardiomyocyte and its mechanism of antiarrhythmia. Method The single ventricular cardiomyocyte was isolat-ed by using enzyme dispersion method and whole-cell clamp-patch technique was used to record L-type calcium current.All data were analyzed using ANOVA. Results AA inhibited Ica-L in a concentration-dependent manner. The application of 3 μmol/L, 10 μmol/L and 20 μmol/L arachidonic acid reduced the density of peak Ica-L from (10.79±0.93)pA/pF to (8.99±0.43)pA/pF to (7.60±0.35)pA/pF and to (5.60±0.30)pA/pF, respctive-ly (n=7, P<0. O1 ). The Ica-Lpartially resumed after washout. The AA up-shifted the I-V curves of Ica-L without changes of their shape,peak and reverse potentials. The AA also markedly shifted the inactivation curve to left, and prolonged the recorvery time from inactivation

  11. Inhibitory effects of Tabebuia impetiginosa inner bark extract on platelet aggregation and vascular smooth muscle cell proliferation through suppressions of arachidonic acid liberation and ERK1/2 MAPK activation. (United States)

    Son, Dong-Ju; Lim, Yong; Park, Young-Hyun; Chang, Sung-Keun; Yun, Yeo-Pyo; Hong, Jin-Tae; Takeoka, Gary R; Lee, Kwang-Geun; Lee, Sung-Eun; Kim, Mi-Ran; Kim, Jeong-Han; Park, Byeoung-Soo


    The antiplatelet and antiproliferative activities of extract of Tabebuia impetiginosa inner bark (taheebo) were investigated using washed rabbit platelets and cultured rat aortic vascular smooth muscle cells (VSMCs) in vitro. n-Hexane, chloroform and ethyl acetate fractions showed marked and selective inhibition of platelet aggregation induced by collagen and arachidonic acid (AA) in a dose-dependent manner. These fractions, especially the chloroform fraction, also significantly suppressed AA liberation induced by collagen in [(3)H]AA-labeled rabbit platelets. The fractions, especially the chloroform fraction, potently inhibited cell proliferation and DNA synthesis induced by platelet derived growth factor (PDGF)-BB, and inhibited the levels of phosphorylated extracellular signal regulated kinase (ERK1/2) mitogen activated protein kinase (MAPK) stimulated by PDGF-BB, in the same concentration range that inhibits VSMC proliferation and DNA synthesis.

  12. A rapid method for determining arachidonic:eicosapentaenoic acid ratios in whole blood lipids: correlation with erythrocyte membrane ratios and validation in a large Italian population of various ages and pathologies

    Directory of Open Access Journals (Sweden)

    Corsetto Paola


    Full Text Available Abstract Background Omega-3 and -6 polyunsaturated fatty acids (LCPUFA, are important for good health conditions. They are present in membrane phospholipids. The ratio of total n-6:n-3 LCPUFA and arachidonic acid:eicosapentaenoic acid (AA and EPA, should not exceed 5:1. Increased intake of n-6 and decreased consumption of n-3 has resulted in much higher, ca 10/15:1 ratio in RBC fatty acids with the possible appearance of a pathological "scenario". The determination of RBC phospholipid LCPUFA contents and ratios is the method of choice for assessing fatty acid status but it is labour intensive and time consuming. Aims of the study [i] To describe and validate a rapid method, suitable for large scale population studies, for total blood fatty acid assay; [ii] to verify a possible correlation between total n-6:n-3 ratio and AA:EPA ratios in RBC phospholipids and in whole-blood total lipids, [iii] to assess usefulness of these ratio as biomarkers of LCPUFA status. Methods 1 Healthy volunteers and patients with various pathologies were recruited. 2 Fatty acid analyses by GC of methyl esters from directly derivatized whole blood total lipids and from RBC phospholipids were performed on fasting blood samples from 1432 subjects categorised according to their age, sex and any existing pathologies. AA:EPA ratio and the total n-6:n-3 ratio were determined. Results AA:EPA ratio is a more sensitive and reliable index for determining changes in total blood fatty acid and it is correlated with the ratio derived from extracted RBC phospholipids. Conclusions The described AA:EPA ratio is a simple, rapid and reliable method for determining n-3 fatty acid status.

  13. Selective Inhibition of Human Group IIA-secreted Phospholipase A2 (hGIIA) Signaling Reveals Arachidonic Acid Metabolism Is Associated with Colocalization of hGIIA to Vimentin in Rheumatoid Synoviocytes* (United States)

    Lee, Lawrence K.; Bryant, Katherine J.; Bouveret, Romaric; Lei, Pei-Wen; Duff, Anthony P.; Harrop, Stephen J.; Huang, Edwin P.; Harvey, Richard P.; Gelb, Michael H.; Gray, Peter P.; Curmi, Paul M.; Cunningham, Anne M.; Church, W. Bret; Scott, Kieran F.


    Human group IIA secreted phospholipase A2 (hGIIA) promotes tumor growth and inflammation and can act independently of its well described catalytic lipase activity via an alternative poorly understood signaling pathway. With six chemically diverse inhibitors we show that it is possible to selectively inhibit hGIIA signaling over catalysis, and x-ray crystal structures illustrate that signaling involves a pharmacologically distinct surface to the catalytic site. We demonstrate in rheumatoid fibroblast-like synoviocytes that non-catalytic signaling is associated with rapid internalization of the enzyme and colocalization with vimentin. Trafficking of exogenous hGIIA was monitored with immunofluorescence studies, which revealed that vimentin localization is disrupted by inhibitors of signaling that belong to a rare class of small molecule inhibitors that modulate protein-protein interactions. This study provides structural and pharmacological evidence for an association between vimentin, hGIIA, and arachidonic acid metabolism in synovial inflammation, avenues for selective interrogation of hGIIA signaling, and new strategies for therapeutic hGIIA inhibitor design. PMID:23482564

  14. 品种与部位对羊肌肉中亚麻酸与花生四烯酸含量的影响%Study on the Linolenic Acid and Arachidonic Acid Content in Different Breeds and Parts of Sheep

    Institute of Scientific and Technical Information of China (English)

    罗玉龙; 杨晶; 刘夏炜; 靳志敏; 段艳; 靳烨


    Linolenic acid and Arachidonic acid content of biceps femoris,triceps brachii and longissimus dorsi from 5 months Sunite sheep,Small tailed han sheep and Bahan F2 sheep were detected by gas chromatography to explore the effect of breeds and anatomical locations.The results showed breeds and anatomical locations had significantly influence on Linolenic acid and Arachidonic acid content.Content of Linolenic acid was the highest in the longissimus muscles of Small tailed han sheep;In the same breed,Arachidonic acid content in the longissimus dorsi significantly higher than other anatomical locations.In the different breeds,content of Arachidonic acid in Sunite sheep was higher than other breeds.Compared comprehensively,content of Arachidonic acid in the longissimus dorsi of Sunite lamb was the highest.As the standard evaluation of mutton nutrition value,meat of Sunite sheep was the better than meat of Small tailed han sheep and Bahan F2 sheep,the longissimus dorsi of Sunite sheep was best.%通过选择5月龄苏尼特羊、小尾寒羊及巴寒F2各5只,每只羊就其背最长肌,股二头肌、臂三头肌3个部位用气相色谱法测定其脂肪酸含量,来进一步研究不同品种不同部位羊肉亚麻酸与花生四烯酸的含量,阐明品种及部位对羊肉中亚麻酸与花生四烯酸含量的影响.结果表明:品种和部位都对羊肉中亚麻酸与花生四烯酸的含量有一定影响,小尾寒羊背最长肌部位的亚麻酸含量最高;同一品种,背最长肌部位花生四烯酸含量显著高于其他部位.不同品种的羊,苏尼特羊的花生四烯酸含量高于小尾寒羊和巴寒F2,综合比较得出苏尼特羊背最长肌部位的花生四烯酸含量最高.以这2种酸作为评价羊肉营养价值的标准时,苏尼特肉质较小尾寒羊和巴寒F2好,其中背最长肌肉质为最佳.

  15. Intake of farmed Atlantic salmon fed soybean oil increases hepatic levels of arachidonic acid-derived oxylipins and ceramides in mice (United States)

    Introduction of vegetable ingredients in fish feed has affected the fatty acid composition in farmed Atlantic salmon (Salmo salar L). Here we investigated how changes in fish feed affected the metabolism of mice fed diets containing fillets from such farmed salmon. We demonstrate that replacement of...

  16. Virus-induced enhancement of arachidonate metabolism by bovine alveolar macrophages in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Laegreid, W.W.; Taylor, S.M.; Leid, R.W.; Silflow, R.M.; Evermann, J.R.; Breeze, R.G.; Liggitt, H.D.


    Virus infection of alveolar macrophages both in vivo and in vitro has been associated with a variety of changes in cellular function. Some of these changes are identical to the effects that arachidonate-derived mediators, prostaglandins, leukotrienes, and hydroxyeicosatetraenoic acids, have on macrophage function. Virus infection of macrophages has been previously shown to increase the output of some arachidonate metabolites, most notably PGE2. However, the effect of virus infection on arachidonate metabolism in general has not been well described. In our experiments, primary cultures of alveolar macrophages obtained from normal cattle by bronchoalveolar lavage, were infected in vitro with parainfluenza type 3 virus. At days 0 to 4 post-infection (p.i.) these cells were labelled with 3H-arachidonic acid and stimulated with either serum-coated zymosan, the calcium ionophore A23187, or phorbol myristate acetate. The complete spectrum of arachidonate-derived metabolites was determined by reverse-phase high performance liquid chromatography with UV and on-line radiometric monitoring of column eluant. The total output of metabolites of arachidonic acid by virus-infected alveolar macrophages was increased over that of noninfected controls (with all stimuli tested) by day 4 p.i. (P less than or equal to 0.05). The production of metabolites by the cyclooxygenase, 12- and 5-lipoxygenase enzyme systems was significantly increased, as was the release of 3H-arachidonate. The lack of stimulus specificity and the increases in arachidonate release suggest that greater substrate availability, due either to increased phospholipase activity or direct virus-membrane interaction, may be responsible for the virus-induced enhancement of metabolite output.

  17. Effect of resveratrol, tyrosol and beta-sitosterol on oxidised low-density lipoprotein-stimulated oxidative stress, arachidonic acid release and prostaglandin E2 synthesis by RAW 264.7 macrophages. (United States)

    Vivancos, Marta; Moreno, Juan J


    Oxidation of LDL is hypothesised as an early and critical event in atherogenesis. Oxidised LDL (oxLDL) favour the transformation of macrophages into foam cells, an important cell involved in atherosclerosis. Furthermore, oxLDL cause multiple changes in macrophage functions. Thus, oxLDL induces certain genes, suppresses others and alters cell lipid metabolism. Consumption of a Mediterranean diet is associated with a low incidence of atherosclerotic disease, but data about the specific dietary constituents involved and mechanisms conferring cardioprotection are still sparse. The aim of the present study was to determine the effect of representative minor components of wine and olive oil on reactive oxygen species and eicosanoid synthesis induced by oxLDL-stimulated macrophages. We observed that exposure to non-toxic oxLDL concentrations leads to the production of H2O2 by RAW 264.7 macrophages and this effect was reverted by apocynin, a NADPH oxidase inhibitor. Moreover, oxLDL induced arachidonic acid (AA) release, cyclo-oxygenase-2 overexpression and subsequent PGE2 release. We observed that resveratrol and tyrosol revert H2O2 production induced by oxLDL as well as AA release and PGE2 synthesis and that these effects were not as a consequence of these compounds interfering with the oxLDL binding to their receptors. Interestingly, beta-sitosterol presence enhances these polyphenol actions. Thus, we found a synergistic action of polyphenols of olive oil and wine and beta-sitosterol of olive oil led to the modulation of the effects of oxLDL on oxidative stress and PGE2 synthesis.

  18. 花生四烯酸、二十二碳六烯酸和二十碳五烯酸在炎症中的作用概述%Roles of arachidonic acid, docosahexaenoic acid and eicosapentaenoic acid in inflammation

    Institute of Scientific and Technical Information of China (English)

    柳泽深; 姜悦; 陈峰


    心脑血管疾病、肿瘤、糖尿病、神经系统疾病、自身免疫等疾病严重危害着人类的生命和健康,并消耗着大量医疗资源。事实上,很多疾病发生和发展的背后都伴随着炎症反应,炎症是众多疾病的病理基础,甚至是导致这些疾病的诱因。炎症本身是机体的防御性反应,但过度的炎症反应和长期慢性炎症会损害机体的稳态。炎症的调节和控制由炎症介质介导,花生四烯酸(arachidonic acid, AA)、二十二碳六烯酸(docosahexaenoic acid, DHA)和二十碳五烯酸(eicosapentaenoic acid, EPA)等长链多不饱和脂肪酸(long-chain polyunsaturated fatty acids, LC-PUFAs)的衍生物是一类重要的调控炎症的介质。炎性细胞间的交流和细胞内信号传递与LC-PUFAs有关。AA经环氧酶和脂氧合酶合成的类二十烷酸主要起促炎作用,但有的也有抗炎作用。DHA和EPA在体内起抗炎作用,由它们合成的消退素(resolvins, Rvs)和保护素(protectin, PD)是重要的抗炎活性物质。DHA和EPA还可以干扰炎性细胞内信号传导途径来抑制炎症反应。本文从炎症与疾病的关系、LC-PUFAs的衍生物及其促炎和抗炎机制等方面综述了AA、DHA和EPA在炎症中的作用。%ABSTRACT:Cardiovascular disease, cancer, diabetes, neurological diseases and autoimmune disease are major threat to human health and long life, and a large amount of medical resources are consumed on the treatment of these diseases. In fact, the progression of these diseases is pointed out to be accompanied by inflammatory response, and inflammation is regarded as pathological basis of many diseases. Normally inflammation itself is a defensive reaction of body, but excessive inflammatory response and chronic inflammation can damage organ homeostasis. On the other side, regulation and control of inflammation can be mediated by inflammatory mediators. It is indicated that derivatives of long-chain polyunsaturated fatty acids

  19. C20∶4和C22∶6对早产儿视功能和认知功能的影响%Effects of Docosahexaenoic and Arachidonic Acid on Visual and Cognitive Function of Premature Infants

    Institute of Scientific and Technical Information of China (English)

    韩宏裕; 苏宜香


    【目的】 探讨补充模拟母乳二十二碳六烯酸(C22∶6 ,DHA)和二十碳四烯酸(C20∶4,AA)水平的脂肪酸对早产儿视功能和认知功能的影响 。【方法】 选取体质量<2 100 g ,胎龄<37周的早产儿32名,分为3组:A组,母乳组11例;B组,传统配方组10例;C组,补 充组11例。B组配方不含DHA和AA,C组配方添加了DHA和AA。补充组配方补充至婴儿体质量达 (2.50±0.10) kg。当胎龄满42周±1周时以鲍秀兰等新生儿行为神经测定方法测认知功能 ;出生后3个月时测双眼视网膜电图。【结果】 补充组早产儿在视功能、认知功能等方面都 与母乳组相近,而传统配方组则低于母乳组和补充组(P<0.05)。【结论】 给予早产儿 补充模拟母乳水平的DHA和AA,可促进其正常的脑发育和视网膜发育,使认知功能和视功能 与母乳喂养的早产儿相近。%【Objective】 To study the effects of docosahexaenoic ac id (DHA) and arachidonic acid (AA) intake on the visual and cognitive function o f preterm infants. 【Methods】 32 preterm infants (gestational age<37 weeks) wer e divided into three groups which were fed with different formula respectively: group A, breast milk(n=11); group B, a conventional formula lacking DHA and AA (n=10); group C, DHA and AA enriched formula (n=11). Group C was stop ped to fed enriched formula when infant's weight reached (2.50±0.10) kg. Cognitiv e function was evaluated by NBNA test when the corrected age of each preterm inf ant was 42 week±7 day, ERG of both eyes was tested at three-months old. The ex periment lasted for three months. 【Results】 Cognitive and visual function of g roup C were similar to group A, however, some indexes of group B were significan tly lower than group A and C (P<0.05). 【Conclusion】 Adding DHA and AA to f ormulas similar to breast milk in amounts, can improve cognitive and visual func tion of preterm infants, and help these infants

  20. Domestication of the high-sugar-tolerant Mortierella alpina on arachidonic acid (ARA) production%花生四烯酸产生菌高山被孢霉的高糖驯化研究

    Institute of Scientific and Technical Information of China (English)

    曾思钰; 凌雪萍; 张长杰; 卢英华


    [目的]提高花生四烯酸(Arachidonic acid,ARA)产量,克服ARA产生菌高山被孢霉(Mortierella alpina)在长期的保存及使用过程中易受到外界条件影响发生退化,从而导致菌种耗糖量降低、影响菌种摄入营养的能力和不利于工业化生产的缺点.[方法]首先采用固体培养基驯化,将菌种逐级涂布于梯度高糖PDA平板(含糖量分别为2%、5%、7%、10%和15%)培养,挑选经固体驯化后能耐受10%高糖浓度平板的菌种,转接到两种含不同氮源的梯度高糖(含糖量分别为3%、4%、5%和6%)液体培养基中进行驯化,最后对驯化后的菌种进行2L发酵罐放大实验.[结果]当培养基中以酵母粉为氮源时,驯化后菌体的最高耗糖量由3 g/(L·d)提高到12 g/(L·d);当培养基中以玉米浆为氮源时,驯化后菌体的最高耗糖量由7 g/(L·d)提高到12 g/(L·d).摇瓶驯化实验结果表明以玉米浆为氮源驯化的菌种发酵效果较好,发酵罐实验结果显示菌体生物量为50 g/L,总油脂为18 g/L,目的产物ARA产量为8g/L.相比未驯化之前的发酵结果,生物量和总油脂含量提高了近3倍,ARA产量提高了近4倍.[结论]经过高糖驯化,菌种的耗糖能力得到提高,生物量、总油脂及ARA的产量也都有所增加,从而可以使菌种在保存和使用过程中不易退化,保持稳定.%[Objective] In order to improve arachidonia acid (ARA) production, and prevent the degeneration of ARA-producing strain Mortierella alpina in long-term culture preservation and cultivation, which could lead to low consumption rate of substrates like carbon source. [Methods] Mortierella alpina strain was first domesticated in high-sugar PDA plate with gradient sugar content (2%, 5%, 7%, 10% and 15%). The strain which grew better in the solid medium containing 10% sugar was then selected and transferred to two liquid high-sugar media with different nitrogen sources to domesticate. The gradient sugar

  1. Oxidation of esterified arachidonate by rat liver microsomes

    Energy Technology Data Exchange (ETDEWEB)

    Davis, H.W.; Suzuki, T.; Schenkman, J.B.


    The authors have previously demonstrated a relationship between phospholipid arachidonate in liver microsomes and malondialdehyde (MDA) formation during lipid peroxidation. In this study arachidonic acid (U-/sup 14/C) was incorporated into rat liver microsomes and NADPH-supported peroxidation was carried out at 37/sup 0/C for 15 minutes. The microsomes were pelleted by centrifugation and the labeled products in the supernatant were isolated by a solid phase method. Pellets were hydrolyzed with phospholipase A/sub 2/ and extracted with diethyl ether and the products from both fractions were separated by reverse phase HPLC. The results show that (1) oxidation occurs in all of the major phospholipids but that phosphatidylethanolamine is the most susceptible; (2) a linear correlation exists between MDA formation and supernatant radioactivity; (3) several different polar products are found in both the supernatant and the hydrolyzed pellet but that the ratios of product peaks in HPLC do not change during the peroxidation, indicating no secondary metabolism or propagation; and (4) cytochrome P-450 is not involved in the peroxidative reactions since no oxidation occurs in the absence of Fe/sup 3 +/ and since product formation is unaffected in the presence of carbon monoxide.

  2. Milk in the island of Chole [Tanzania] is high in lauric, myristic, arachidonic and docosahexaenoic acids, and low in linoleic acid - Reconstructed diet of infants born to our ancestors living in tropical coastal regions

    NARCIS (Netherlands)

    Kuipers, Remko S.; Smit, Ella N.; van der Meulen, Jan; Dijck-Brouwer, D. A. Janneke; Boersma, E. Rudy; Muskiet, Frits A. J.


    Background: We need information on the diet on which our genes evolved. Objective: We studied the milk fatty acid [FA] composition of mothers living in the island of Chole [Tanzania, Indian Ocean]. These mothers have high intakes of boiled marine fish and coconut, and consume plenty amount of fruits

  3. Optimization of Mortierella Isabellina culture medium conditions in fermentation of arachidonic acid by response surface methodology%响应面法优化深黄被孢霉发酵生产花生四烯酸的培养基条件

    Institute of Scientific and Technical Information of China (English)

    于新新; 于长青


    为了降低深黄被孢霉YZ-124生产花生四烯酸的成本,研究了不同添加量的玉米黄浆水对发酵的影响,与葡萄糖培养基相比,在发酵培养基中添加一定量的玉米黄浆水对发酵产量无显著影响.在单因素实验的基础上,利用Design Expert设计了响应面实验,研究了葡萄糖浓度、不同添加量的玉米黄浆水和初始pH对花生四烯酸产量的影响.结果表明,最佳的培养基条件是葡萄糖浓度为90g/L、添加体积分数为25%的玉米黄浆水、初始pH6时,花生四烯酸(ARA)产量达到最大,为3.11g/L.%Fermentative production arachidonic acid of Mortierella isabellina using waste water from maize paste was investigated to reduce the cost,adding waste water from maize paste into the culture medium had no obvious effect on the fermentation. On the basis of single factor tests .response surface analysis was designed by Design Expert,and the glucose concentration,different quality of waste water from maize paste and pH were investigated. The results showed that the optimal culture medium conditions were the glucose concentration was 90g/L,the maize paste waste water was 25% in the culture medium and pH was 6. Under this condition,the yield of arachidonic acid was 3.11g/L.

  4. Subchronic (13-week) oral toxicity study, preceded by an in utero exposure phase, with arachidonate-enriched triglyceride oil (SUNTGA40S) in rats

    NARCIS (Netherlands)

    Lina, B.A.R.; Wolterbeek, A.P.M.; Suwa, Y.; Fujikawa, S.; Ishikura, Y.; Tsuda, S.; Dohnalek, M.


    Polyunsaturated fatty acids (PUFAs), such as arachidonic acid (ARA) and docosahexaenoic acid (DHA) are natural constituents found in human milk, fish oil or egg yolk. Until recently, infant formulas, though providing the essential fatty acid precursors for these PUFAs, did not contain preformed ARA

  5. Effects of α-linolenic acid and arachidonic acid on the expressions of nuclear transcription factor Nrf 2 and phase Ⅰ metabolism enzyme CYP7A1%α-亚麻酸和花生四烯酸对Nrf2和Ⅰ相代谢酶CYP7A1表达的影响

    Institute of Scientific and Technical Information of China (English)

    张金铭; 张秀英; 郝丽红; 马丽梅


    为了检测α-亚麻酸(α-linolenic acid,ALA)和花生四烯酸(arachidonic acid,AA)对于人肝癌细胞系(HepG2细胞)中核转录因子Nrf 2和Ⅰ相代谢酶胆固醇7α-羟化酶(CYP7A1)的mRNA和蛋白质表达的影响,并探究CYP7A1是否受Nrf2的调控,试验以不同浓度的ALA和AA诱导HepG2细胞24 h,之后采用Real-time PCR法和Western-blot法分别检测HepG2细胞内Nrf 2和CYP7A1的mRNA和蛋白质的表达量.结果表明:当使ALA浓度为0.25,0.5,1 mmol/L作用于HepG2细胞时,Nrf2和CYP7A1的mRNA和蛋白质的表达量相比于细胞对照均呈剂量依赖性升高(P<0.01);当使AA浓度为0.25,0.5,1 mmol/L作用于HepG2细胞时,Nrf 2的mRNA和蛋白质的表达量相比于细胞对照呈剂量依赖性升高(P<0.01),但CYP7A1的mRNA和蛋白质的表达量相比于细胞对照则呈剂量依赖性减少(P<0.01).说明不同剂量的ALA和AA对Nrf 2和CYP7A1的mRNA和蛋白质的表达量影响不同,Nrf 2和CYP7A1呈正相关或负相关.

  6. Sheep erythrocyte membrane binding and transfer of long-chain fatty acids

    DEFF Research Database (Denmark)

    Bojesen, Inge Norby; Bojesen, Eigil


    Palmitic acid, oleic acid, linoleic acid, arachidonic acid, sheep erythrocyte ghosts, transporting elements, transport kinetics, fatty acid transport, transport rate constants......Palmitic acid, oleic acid, linoleic acid, arachidonic acid, sheep erythrocyte ghosts, transporting elements, transport kinetics, fatty acid transport, transport rate constants...

  7. Formation of isoprostane bicyclic endoperoxides from the autoxidation of cholesteryl arachidonate. (United States)

    Yin, Huiyong; Havrilla, Christine M; Morrow, Jason D; Porter, Ned A


    Autoxidation of polyunsaturated fatty acids and esters leads to a complex mixture containing hydroperoxides and cyclic peroxides. Prostaglandin bicyclic endoperoxides have been detected from the autoxidation of cholesteryl arachidonate by LC-MS and GC-MS techniques. All four possible types (I-IV) of bicyclic endoperoxides have been found starting from different regioisomeric hydroperoxides of cholesteryl arachidonate. Furthermore, the stereochemistry of Type IV bicyclic endoperoxides has been determined by conversion to pentafluorobenzyl (PFB) ester, trimethylsilyl (TMS) derivatives, and comparison with synthetic standards by the use of GC-MS. All eight possible diastereomers of the derivatized isoprostanes were observed and were separated by gas chromatography. The bicyclic endoperoxides with the two alkyl chains syn on the cyclopentane ring were formed preferentially to those with anti configuration, a result anticipated from earlier work. Substantial amounts of the anti-substituted isoprostanes, including PGF(2)(alpha), were, however, observed in the product mixture.

  8. BIRM 270: a novel inhibitor of arachidonate release that blocks leukotriene B4 and platelet-activating factor biosynthesis in human neutrophils. (United States)

    Farina, P R; Graham, A G; Hoffman, A F; Watrous, J M; Borgeat, P; Nadeau, M; Hansen, G; Dinallo, R M; Adams, J; Miao, C K


    (S)-N-[2-Cyclohexyl-1-(2-pyridinyl)ethyl]-5-methyl-2-benzoxazolamine+ ++ (BIRM 270) was identified as a potent and enantiomerically selective inhibitor of calcium ionophore A23187-stimulated leukotriene B4 biosynthesis in human neutrophils. The (S)- and (R)-enantiomers exhibited IC50 values of 1 nM and 40 nM, respectively. BIRM 270 did not inhibit 5-lipoxygenase activity in a cell-free assay. In addition, the compound did not interfere with the conversion of exogenous 5-lipoxygenase substrate (15S)-hydroperoxyeicosatetraenoic acid to (5S, 15S)-dihydroxyeicosatetraenoic acid in intact, ionophore-stimulated neutrophils. Under the same experimental conditions, BIRM 270 inhibited the production of 5-lipoxygenase products from endogenous substrate, suggesting that the compound affected arachidonate availability rather than metabolism. Consistent with this concept, the inhibition of leukotriene B4 biosynthesis by BIRM 270 was overcome by the addition of exogenous arachidonic acid to the leukocyte preparation. Direct measurement of free arachidonate by gas chromatography-mass spectrometry confirmed that BIRM 270 inhibited arachidonate release from ionophore-stimulated neutrophils. The compound did not affect arachidonate reacylation. The blockage of arachidonate release coincided with inhibition of leukotriene B4 biosynthesis in these cells. BIRM 270 also inhibited ionophore-stimulated platelet-activating factor biosynthesis by human neutrophils. Although these results suggest that BIRM 270 inhibited phospholipase A2-mediated deacylation of membrane phospholipids, the compound did not directly inhibit the high molecular weight, cytosolic phospholipase A2 derived from human neutrophils or U937 cells. Thus, suppression of arachidonate mobilization by BIRM 270 may be due to indirect inhibition of intracellular phospholipase A2 or to inhibition of another acylhydrolase activity.

  9. Synergism interaction between arachidonic acid by 5-hydroxytryptamine in human platelet aggregation is mediated through multiple signalling pathways%多种信号途径介导花生四烯酸与5-羟色胺在促人类血小板凝集中的协同作用

    Institute of Scientific and Technical Information of China (English)

    Sheikh Arshad SAEED; Huma RASHEED; Anwar-ul-Hassan GILANI


    AIM: To examine the signalling mechanisms involved in the synergistic interaction of 5-hydroxytryptamine (5-HT)and arachidonic acid (AA) in human platelet aggregation. METHODS: Blood was obtained from healthy human subjects, mixed with 3.8 % sodium citrate (9:1), and centrifuged to prepare platelet rich plasma (PRP). Aggregation was monitored using a Dual-channel Lumi-aggregometer. The agonist-induced influx of Ca2+ was measured using Fura-2 AM. TXA2 formation was studied using radiochemical method. RESULTS: Subthreshold concentration of 5-HT (2 μmol/L) potentiated the effect of low dose of AA (0.2 mmol/L) in human platelets. This synergistic effect was blocked by 5-HT2 receptor antagonist (methysergide IC50=5.2 nmol/L; cyproheptadine IC50=0.6 nmol/L), and thromboxane A2 receptor antagonist (SQ 29 548; IC50=30 nmol/L), showing that the effect is receptor-mediated.To examine the down-stream signalling pathways, we found that such an interaction was inhibited by calcium channel blockers (diltiazem; IC50=3 μmol/L and verapamil; IC50=5 μmol/L), phospholipase C (PLC) inhibitor (U73122;IC50=4 μmol/L), cyclooxygenase inhibitor, (indomethacin; IC50=0.2 μmol/L) and mitogen-activated protein (MAP)kinase inhibitor (PD98059; IC50=3 μmol/L). The effect was also inhibited by a specific tyrosine light chain kinase (TLCK) inhibitor, herbimycin A with IC50 value of 5 μmol/L. Pretreatment of platelet with 5-HT and AA induced rise in intracellular calcium and this effect was blocked by verapamil. CONCLUSION: The synergism between 5-HT and AA in platelet aggregation involves activation of PLC/Ca2+, COX, and MAP kinase pathways.

  10. Association between polymorphisms of arachidonate 12-lipoxygenase (ALOX12 and schizophrenia in a Korean population

    Directory of Open Access Journals (Sweden)

    Park Jin


    Full Text Available Abstract Arachidonic acid (AA, an essential polyunsaturated fatty acid, is one of the major components of neural membranes, which show an altered phospholipid composition in schizophrenia. Arachidonate 12-lipoxygenase (ALOX12, an important enzyme, metabolizes AA to 12-HPETE, which affects catecholamine synthesis. However, research has yet to show the genetic association between ALOX12 and schizophrenia. Therefore, we investigated single nucleotide polymorphisms (SNP of the ALOX12 gene in schizophrenia, recruiting patients with schizophrenia (n = 289 and normal controls (n = 306 from a Korean population. We selected three SNPs (rs1126667, rs434473, and rs1042357 of the ALOX12 gene and genotyped them by direct sequencing. We reviewed the schizophrenic patients' medical records and assessed them clinically using the Brief Psychiatric Rating Scale (BPRS, the Scale for the Assessment of Negative Symptoms (SANS, and the Operational Criteria Checklist (OPCRIT. Then we statistically analyzed the genetic associations between the SNPs and schizophrenia, finding a genetic association between both rs1126667 and rs1042357 and schizophrenia, in the recessive model (p = 0.015 and 0.015, respectively. We also found an association between rs434473 and negative symptoms, defined through a factor analysis of the OPCRIT data (p = 0.040. Consequently, we suggest that SNPs of the ALOX12 gene might be associated with schizophrenia and negative symptoms in this Korean population. These weak positives require additional study.

  11. Low Penetrance Alleles in Colorectal Cancer: the arachidonic acid pathway

    NARCIS (Netherlands)

    C.L.E. Siezen


    textabstractIn summary, we can conclude that we have successfully identified low penetrance alleles in the PPAR., PLA2G2A and ALOX15 genes, conferring differential colorectal adenoma risk, and two such alleles in the PTGS2 gene, one of which is also involved in colorectal cancer risk. These resul

  12. Effect of arachidonic acid supplementation and cyclooxygenase/lipoxygenase inhibition on the development of early bovine embryos Influência do ácido araquidónico e da inibição da ciclo-oxigenase ou lipo-oxigenase no desenvolvimento inicial de embriões bovinos

    Directory of Open Access Journals (Sweden)

    Rosa Maria Pereira


    Full Text Available The effect of arachidonic acid (AA cascade on bovine embryo development in a granulosa cell co-culture system was studied. Arachidonic acid (100 µM was supplemented from 1-cell to 8-16 cell block stage (first three days of co-culture and from 1-cell to hatching. Specific cyclooxygenase (indomethacin, 28 µM and lipoxygenase (nordihydroguaiaretic acid - NDGA, 28 µM inhibitors were used from 1-cell to 8-16 cell block stage with AA. Embryo development was assessed by cleavage, day 7-day 8 and hatched embryo rates and by measuring growth rates through development stages found in days 7-10 of culture (day 0 = insemination day. Embryo quality was scored at day 8. A 6.5-10.4% increase on cleavage rate after AA supplementation was found. This AA supplementation from 1-cell to hatching delayed embryo growth rate beyond day 7 and a reduction on hatching rate was detected. When AA supplementation was restricted to the first three days of co-culture those negative effects were overcome. Also, indomethacin and NDGA prevented the positive effect of AA and induced a significant reduction on cleavage, respectively. NDGA further decreased day 7 embryo rate and quality. Results suggest that AA has a two-phase action on bovine embryos, promoting early development and impairing embryo growth from day 7 onwards and hatching rates. Both cyclooxygenase and lipoxygenase were found to be important pathways to promote cleavage.Estudou-se a influência da cascata do ácido araquidónico (AA no desenvolvimento de embriões bovinos produzidos in vitro em co-cultura com células da granulosa. Os embriões foram suplementados com AA (100 µM desde o estádio de 1 célula até 8-16 células (primeiros três dias de co-cultura ou até a eclosão. Introduziram-se inibidores específicos da ciclo-oxigenase (indometacina, 28 µM e da lipo-oxigenase (ácido nordihidroguaiarético - NDGA, 28 µM, juntamente com o ácido araquidónico, desde o estádio de 1 célula até 8-16 c

  13. Comparison of increased arachidonic acid content in Myrmecia incisa cultured during the course of nitrogen or phosphorus starvation%氮饥饿与磷饥饿促使缺刻缘绿藻花生四烯酸含量增加的比较

    Institute of Scientific and Technical Information of China (English)

    童牧; 于水燕; 欧阳珑玲; 周志刚


    The growth rate and biomass,contents of arachidonic acid(AA) and other fatty acids in Myrmecia incisa Reisigl H4301, a freshwater green microalga rich in AA, were comparatively studied while cultured between nitrogen and phosphorus starvation under different light intensities. It was found that either nitrogen or phosphorus starvation could cause a reduced growth rate of this microalga as well as a resultant biomass.If grown under a lower light intensity [ 60 μmol photons/( m2 · s) ], the lowest average growth rate [ 0.025 g/( d · L) ] of this microalga resulted from phosphorus starvation, which was nearly half of the growth rate while grown in a complete BG-11 medium. Both of nitrogen and phosphorus starvation could increase the contents of total fatty acids and AA,however, when this alga was exposed to low light intensity the positive effect of phosphorus starvation was limited. High light intensity [ 200 μmol photons/( m2 · s ) ] was not beneficial to the synthesis and accumulation of AA no matter how this microalga was cultured in the complete or nitrogen-free or phosphorus-free media. The AA content gradually increased accompanying with a decrease of linoleic acid content during the starvation. However, the oleic acid percentage also gradually increased which limited more significantly the accumulation of AA in this microalga grown under phosphorus starvation than nitrogen one. Based on the composition changes of every species of fatty acids, the main synthesis metabolic pathway of AA suggested that it proceeded from linoleic acid to γ-linolenic acid and then to 20:3ω6 under nitrogen or phosphate starvation,and that the Δ6 desaturase was a rate-limiting enzyme. The step in which ω3 desaturase played was down regulated by nitrogen or phosphorus starvation, thus ensuring the synthesis and accumulation of AA positively. Nitrogen starvation blocked the protein synthesis, and phosphorus starvation caused the disorders of nucleic acid, carbohydrate and

  14. Arachidonate metabolism increases as rat alveolar type II cells differentiate in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Lipchik, R.J.; Chauncey, J.B.; Paine, R.; Simon, R.H.; Peters-Golden, M. (Univ. of Michigan, Ann Arbor (USA))


    Rat type II alveolar epithelial cells are known to undergo morphological and functional changes when maintained in culture for several days. Having previously demonstrated that these cells can deacylate free arachidonic acid (AA) and metabolize it to products of the cyclooxygenase pathway, the present study was undertaken to determine whether in vitro differentiation was accompanied by alterations in the availability and metabolism of AA. We assessed the constitutive and ionophore A23187-induced deacylation and metabolism of endogenous AA, as well as the metabolism of exogenously supplied AA, in primary cultures of rat type II cells at days 2, 4, and 7 after isolation. Levels of free endogenous AA were increased at day 4, whereas eicosanoid synthesis, predominantly prostaglandin E2 and prostacyclin, increased markedly only at day 7. A similar time course of augmentation of prostanoid release was seen in response to exogenous AA. Type II cells cultured on fibronectin, intended to hasten cell flattening and spreading, demonstrated accelerated increases in available free AA in response to A23187; cells cultured on basement membrane derived from Engelbreth-Holm-Swarm mouse sarcoma, known to maintain the type II phenotype, exhibited diminished levels of available free AA. From these findings, we conclude that alterations in arachidonate metabolism are linked to alterations in cellular phenotype. The potentiation of eicosanoid synthesis accompanying in vitro differentiation suggests a possible role for the alveolar epithelium in the modulation of inflammation and fibrosis in the distal lung.

  15. Omega-3 Fatty Acids and Inflammatory Processes

    Directory of Open Access Journals (Sweden)

    Philip C. Calder


    Full Text Available Long chain fatty acids influence inflammation through a variety of mechanisms; many of these are mediated by, or at least associated with, changes in fatty acid composition of cell membranes. Changes in these compositions can modify membrane fluidity, cell signaling leading to altered gene expression, and the pattern of lipid mediator production. Cell involved in the inflammatory response are typically rich in the n-6 fatty acid arachidonic acid, but the contents of arachidonic acid and of the n-3 fatty acids eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA can be altered through oral administration of EPA and DHA. Eicosanoids produced from arachidonic acid have roles in inflammation. EPA also gives rise to eicosanoids and these often have differing properties from those of arachidonic acid-derived eicosanoids. EPA and DHA give rise to newly discovered resolvins which are anti-inflammatory and inflammation resolving. Increased membrane content of EPA and DHA (and decreased arachidonic acid content results in a changed pattern of production of eicosanoids and resolvins. Changing the fatty acid composition of cells involved in the inflammatory response also affects production of peptide mediators of inflammation (adhesion molecules, cytokines etc.. Thus, the fatty acid composition of cells involved in the inflammatory response influences their function; the contents of arachidonic acid, EPA and DHA appear to be especially important. The anti-inflammatory effects of marine n-3 PUFAs suggest that they may be useful as therapeutic agents in disorders with an inflammatory component.

  16. Metabolically Engineered Fungal Cells With Increased Content Of Polyunsaturated Fatty Acids

    DEFF Research Database (Denmark)


    This invention relates to the production of fatty acids and particularly to the production of the polyunsaturated fatty acids (PUFAs) arachidonic acid (ARA) and eicosapentaenoic acid (EPA) in genetically engineered fungal cells, in particular, to metabolically engineered Saccharomyces cerevisiae...

  17. Arachidonic Acid Metabolites Increased in Ulcerative Colitis Rats with Damp-heat Syndrome and were Down-regulated by Huanqin Decoction%花生四烯酸代谢物在湿热型溃疡性结肠炎大鼠的表达与调节

    Institute of Scientific and Technical Information of China (English)

    郑学宝; 戴世学; 邹颖


    Objective :To explore the role of arachidonic acid metabolites (AAMs) in ulcerative colitis (UC) rats with damp -heat syndrome (DHS), and to observe the effect of Huanqin decoction on the model. Methods: 45 rats were put into an artificial bioclimatic chamber with temperature of 36℃, humidity of 98% and feed in fat and sugar forage to establish the model for 4 weeks. After a one - week treatment by Huanqin decoction ( group H, n = 13) and by mesalazine (group M, n = 12), concentration of PGE2, LTB4, PAF and COX -2 in serum and colon were detected using ELISA.Triglycercide (TG) and T-cholesterol (CH) were also tested to reflect the degree of DHS, so were the fat globules in the feces. Histological scores for colon were rated through naked eyes to assess the severity of UC. Besides, the relations between the upper indexes were calculated by Pearson analysis. Results: Compared with the control group ( n = 15 ),PGE2, PAF, LTB4 and COX - 2 increased significantly in the model rats ( n = 12,P < 0.05 ). PGE2 and LTB4 in group H were obviously lower than that in group M, so were the TG, CH and feces fat globules(all P<0.05). But there was no statistical difference of the histological scores between group H and M. Pearson analysis showed there was a definited positive relationship between any two of PGE2,PAF,LTB4, COX -2, TG, CH, feces fat globules and histological scores (r > 0. 930, P < 0. 01 ). Conclsion: AAMs increased apparently in UC rats with DHS, which was closely related to the indexes involving both UC and damp - heat syndrome. It was proved to be more effective of Huangqin decoction to down -regulate PGE2, LTB4, TG, CH and and feces fat globules than mesalazine.%目的:探讨花生四烯酸(AA)代谢物在湿热型溃疡性结肠炎(UC)大鼠发病的作用以及黄芩汤的调节.方法:采用高脂高糖饲料结合人工气候箱法造成大鼠湿热,使用三硝基苯磺酸灌肠造成湿热型UC模型;将造模大鼠分为模型组(n=12)

  18. Comparison of arachidonate metabolism by alveolar macrophages from bighorn and domestic sheep. (United States)

    Silflow, R M; Foreyt, W J; Taylor, S M; Laegreid, W W; Liggitt, H D; Leid, R W


    We have defined the metabolites of arachidonic acid (AA) secreted by alveolar macrophages (AMs) of bighorn sheep and domestic sheep in response to three agents: calcium ionophore A23187, phorbol myristate acetate (PMA), and opsonized zymosan. Cells were labeled with [3H]AA prior to stimulation and 11 tritiated metabolites, including prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs), and hydroxyeicosatetraenoic acids (HETEs), were detected and quantitated by high-performance liquid chromotography and radiometry. Zymosan stimulation resulted in the release of significantly elevated quantities (P less than 0.05), of LTB4, [5(S), 12(R)-dihydroxy-6,14-cis-8,10-trans-eicosatetraenoic acid], 5-HETE, [5(S)-hydroxyeicosatetraenoic acid], and the nonenzymatic isomers of LTB4, [LTB I, 5(S),12(R)-6-trans-LTB4] and LTB II, [5(S), 12(S)-6-trans-LTB4], from domestic sheep AM when compared to bighorn sheep AM. Phorbol myristate acetate (PMA) stimulation released significantly elevated quantities (P less than 0.04), of TXB2, (thromboxane B2), HHT, [12(S)-12-hydroxy-5,8,10-heptadecaenoic acid], LTB I, LTB II, and 15-HETE, [15(S)-hydroxyeicosatetraenoic acid] from domestic sheep AMs when compared to bighorn sheep AMs. However, after A23187 challenge, only 15-HETE was significantly elevated (P less than 0.04) in domestic sheep AMs when compared to bighorn sheep AMs. These clear differences in AA metabolism of AMs obtained from bighorn and domestic sheep in response to three different agonists suggest not only different control mechanisms for lung metabolism of AA in the two species, but also suggest that differences in the metabolites released may lead to quite different regulation of lung defense mechanisms in the two sheep species.

  19. Carboxylic Acid Ionophores as Probes of the Role of Calcium in Biological Systems (United States)

    Reed, P. W.


    The biological effects of calcium ionophores are described, focusing on arachidonic acid oxygenation, and the formation of a number of oxygenated metabolites of arachidonic acid. These metabolites are involved in a number of bodily functions, and their production may be regulated by calcium.

  20. Urinary prostaglandin E and vasopressin excretion in essential fatty acid-deficient rats

    DEFF Research Database (Denmark)

    Hansen, Harald S.; Jensen, B.


    and the (n-3) rats, even though large differences were found in the percentage of arachidonic acid (20:4[n-6]), icosapentaenoic acid (20:5[n-3]), and icosatrienoic acid (20:3[n-9]) of total kidney fatty acids as well as of kidney phosphatidylinositol fatty acids. Fractionation of urine extracts on high...... an arachidonic acid pool, which is rather resistant to restriction in dietary linoleate. © 1983 American Oil Chemists' Society (AOCS)....

  1. Essential fatty acid nutrition of the American alligator (Alligator mississippiensis). (United States)

    Staton, M A; Edwards, H M; Brisbin, I L; Joanen, T; McNease, L


    The essential fatty acid (EFA) nutrition of young American alligators (Alligator mississippiensis) was examined by feeding a variety of fats/oils with potential EFA activity. Over a 12-wk period, alligators fed diets containing 2.5 or 5.0% chicken liver oil grew longer and heavier and converted feed to body mass more efficiently than alligators fed other fat/oil combinations that lacked or contained only trace amounts of arachidonic acid [20:4(n-6)]. Alligators fed an EFA-deficient diet (containing only coconut fat as the dietary fat) were the slowest-growing animals and converted feed to body mass least efficiently. However, over a 41-wk feeding period, alligators fed this diet showed no obvious external signs of deficiency other than being reduced in size and unthrifty. Fatty acid composition of heart, liver, muscle, skin and adipose tissue lipids was influenced markedly by dietary fat composition. Tissues varied significantly in response to dietary fat composition. Heart lipids contained the lowest levels of short- and medium-chain fatty acids and the highest levels of arachidonic acid. Arachidonic acid levels were less influenced by diet than were levels of other 20- and 22-carbon polyunsaturated fatty acids. Radiotracer studies indicated that linoleic acid was converted to arachidonic acid in the liver. Nevertheless, tissue arachidonic acid levels also appeared to be maintained by concentration from dietary sources and selective conservation. It appears that a dietary source of arachidonic acid may be required for a maximum rate of growth.

  2. Effects of ω-3 polyunsaturated fatty acids on prostaglandin E-2 and arachidonic acid in rats with senile dementia%ω-3多不饱和脂肪酸对老年痴呆大鼠前列腺素E2、花生四烯酸的影响

    Institute of Scientific and Technical Information of China (English)

    赵秀娟; 冯亚青; 李文景; 刘月欣; 张振凤; 吕佩源


    Objective To investigate the mechanism of ω-3 polyunsaturated fatty acids in senile dementi-a. Methods The normal 15 months old Wistar rats were randomly divided into normal control,model group andre-cape latency time and mistaken times were evaluated by using the step down test. The content of serum PGE2 and urachidonic acid(AA),EPA and DHA of cerebral tissue in rats were detected. Results The lingeringly latency and error times were ( 264.83±16.99) s and (4.8±1.7) times in control group, ( 189.26±31.42)s and ( 9.6± 2.2) times in model group, (230.88±29.35) s and (7.3±2.2) times in treatment group, respectively. Differences in three groups were very significantly by analyses of variance(F=20.114, F=13.638, P=0.000). Compared with model group, control group and treatment group had lingeringly latency(LSD-t=6.332,P=0.000 and LSD-t =3.987, P=0.002, respectively) and less error times (LSD-t=5.221, P=0.000 and LSD-t=3.502, P= 0.019,respectively). Serum PGE2 were in control group, model group and treatment group were very significantly by analyses of variance(F=6.851 , P=0.004). Compared with model group,control group had less serum PGE2 (LSD-t=3.684, P=0.001 ). Compared with model group,ω-3 polyunsaturated fatty acids chould decrease serum PGE2( LSD-t=2.152, P=0.041 ). AA, EPA and DHA of cerebral tissue in control group, in model group, in treatment group, respectively. Differences in three groups were very significantly by analyses of variance (F=5.538, P=0.010, F=4.240, P=0.025, F=4.633, P=0.019). Compared with model group,ω-3 polyunsaturat-ed fatty acids could decrease A A(LSD-t=2.273, P=0.031) and increase EPA and D HA (LSD-t=2.428, P= 0.022,LSD-t=2.520, P=0.018,respectively). Conclusions ω-3 polyunsaturated fatty acids can improve learning-memory function in rats,change the proportion of AA,EPA and DHA in cerebral tissue and prevent senile dementia.%目的 探讨ω-3多不饱和脂肪酸治疗老年痴呆的可能机制.方法 将15月龄雌性健

  3. The European Food Safety Authority recommendation for polyunsaturated fatty acid composition of infant formula overrules breast milk, puts infants at risk, and should be revised. (United States)

    Crawford, Michael A; Wang, Yiqun; Forsyth, Stewart; Brenna, J Thomas


    The European Food Safety Authority (EFSA) has concluded from a limited review of the literature that although docosahexaenoic acid (DHA) is required for infant formula, arachidonic acid is not required "even in the presence of DHA" (EFSA Journal, 12 (2014) 3760). This flawed opinion is grounded in human trials which tested functionality of DHA in neural outcomes and included arachidonic acid ostensibly to support growth. The EFSA report mistakes a nutrient ubiquitous in the diets of newborn infants, through breast milk and with wide-ranging health and neurodevelopmental effects, for an optional drug targeted to a particular outcome that is properly excluded when no benefit is found for that particular outcome. Arachidonic acid has very different biological functions compared to DHA, for example, arachidonic acid has unique functions in the vasculature and in specific aspects of immunity. Indeed, the overwhelming majority of trials include both DHA and arachidonic acid, and test development specific to DHA such as neural and visual development. DHA suppresses membrane arachidonic acid concentrations and its function. An infant formula with DHA and no arachidonic acid runs the risk of cardio and cerebrovascular morbidity and even mortality through suppression of the favorable oxylipin derivatives of arachidonic acid. The EFSA recommendation overruling breast milk composition should be revised forthwith, otherwise being unsafe, ungrounded in most of the evidence, and risking lifelong disability.

  4. Toxicological evaluation of arachidonic acid (ARA)-rich oil and docosahexaenoic acid (DHA)-rich oil. (United States)

    Lewis, Kara D; Huang, Weifeng; Zheng, Xiaohui; Jiang, Yue; Feldman, Robin S; Falk, Michael C


    The safety of DHA-rich oil from Schizochytrium sp. and ARA-rich oil from Mortierella alpina was separately evaluated by testing for gene mutations, clastogenicity, and aneugenicity, and by conducting 28-day and 90-day dietary studies in Wistar rats. The results of all genotoxicity tests were negative. The 28-day and 90-day studies involved dietary exposure to 1000, 2500, and 5000 mg per kg bw of the DHA-rich and ARA-rich oils and two control diets: water and corn oil (vehicle control). There were no treatment-related effects of either the DHA-rich or ARA-rich oils on clinical observations, body weight, food consumption, behavior, hematology, clinical chemistry, coagulation, urinalysis parameters, or necropsy findings. Increases in cholesterol and triglyceride levels were considered related to a high oil diet and non-adverse. The no observable adverse effect level (NOAEL) for both the DHA-rich and ARA-rich oils was 5000 mg per kg bw, the highest dose tested. The results confirm that these oils possess toxicity profiles similar to those of other currently marketed oils and support the safety of DHA-rich oil from Schizochytrium sp. and ARA-rich oil from Mortierella alpina for their proposed uses in food.

  5. n-3 Polyunsaturated Fatty Acids and their Role in Cancer Chemoprevention


    Gu, Zhennan; Shan, Kai; Chen, Haiqin; Chen, Yong Q.


    Polyunsaturated fatty acids (PUFAs), including omega-3 (n-3) and omega-6 (n-6) PUFAs, are essential for human health. Recent research shows n-3 PUFAs and their mediators can inhibit inflammation, angiogenesis and cancer via multiple mechanisms, including reduced release of n-6 fatty acid arachidonic acid from cell membranes, inhibition of enzymatic activities, and direct competition with arachidonic acid for enzymatic conversions. In this review, we discuss inflammation-related cancer, anti-i...

  6. Effects of Fish Oil Diet and Age on the Fatty Acid Composition and the Endogenous Lipase Activity in Mouse Brain. (United States)

    Suzuki, H; Jin, Z; Wada, O


    The influences of a fish oil diet and aging on the fatty acid composition in mouse brain, and the release of polyunsaturated fatty acids from brain membranes by endogenous lipase were studied. The changes in brain fatty acid composition with aging were determined in 5-weeks, 5-months and 19-months old mice fed on a commercial chow. Mice of different ages were also fed a fish oil or lard diet for 30 days, and the influence of the diets on brain fatty acid composition and endogenous lipase activity was analyzed. In aged mice fed on a commercial chow brain arachidonic acid and docosahexaenoic acid (%) decreased significantly, whereas blood arachidonic acid (%) increased and docosahexaenoic acid (%) did not change. The percentages of brain docosahexaenoic acid were significantly higher but those of arachidonic acid were lower in the fish oil diet group than in the lard diet group. However, there were no significant differences in the endogenous lipase activity between the different age or dietary groups. The release of arachidonic acid showed a tendency to decrease and docosahexaenoic acid to increase in mice fed on the fish oil diet. These results suggest that dietary lipids affect the percentages of arachidonic and docosahexaenoic acids which are released by the endogenous lipase in brain although the decreases in brain polyunsaturated fatty acid content with aging are not due to the enzyme activation, and dietary lipids do not influence the enzyme activity.

  7. Specific high-affinity binding of fatty acids to epidermal cytosolic proteins

    Energy Technology Data Exchange (ETDEWEB)

    Raza, H.; Chung, W.L.; Mukhtar, H. (Department of Dermatology, University Hospitals of Cleveland, Case Western Reserve University, OH (USA))


    Cytosol from rat, mouse, and human skin or rat epidermis was incubated with (3H)arachidonic acid, (14C)retinoic acid, (14C)oleic acid, (3H)leukotriene A4, (3H)prostaglandin E2 (PGE2) or (3H) 15-hydroxyeicosatetraenoic acid (15-HETE), and protein-bound ligands were separated using Lipidex-1000 at 4C to assess the binding specificity. The binding of oleic acid and arachidonic acid with rat epidermal cytosol was rapid, saturable, and reversible. Binding of oleic acid was competed out with the simultaneous addition of other ligands and found to be in the following order: arachidonic acid greater than oleic acid greater than linoleic acid greater than lauric acid greater than leukotriene A4 greater than 15-HETE = PGE1 greater than PGE2 = PGF2. Scatchard analysis of the binding with arachidonic acid, oleic acid, and retinoic acid revealed high-affinity binding sites with the dissociation constant in the nM range. SDS-PAGE analysis of the oleic acid-bound epidermal cytosolic protein(s) revealed maximum binding at the 14.5 kDa region. The presence of the fatty acid-binding protein in epidermal cytosol and its binding to fatty acids and retinoic acid may be of significance both in the trafficking and the metabolism of fatty acids and retinoids across the skin.

  8. Synthesis of long-chain polyunsaturated fatty acids in preterm newborns fed formula with long-chain polyunsaturated fatty acids

    NARCIS (Netherlands)

    Carnielli, Virgilio P.; Simonato, Manuela; Verlato, Giovanna; Luijendijk, Ingrid; De Curtis, Mario; Sauer, Pieter J. J.; Cogo, Paola E.


    Background: Docosahexaenoic acid (DHA) and arachidonic acid (AA) are long-chain polyunsaturated fatty acids (LCPs) that play pivotal roles in growth and neurodevelopment. Objective: We aimed to quantify the synthesis of LCPs in preterm infants fed infant formula containing LCPs. Design: Twenty-two p

  9. Relationships between Arachidonic Acid, Uterine Activity and Metabolic Regulation of Placental Lactogen Secretion. (United States)


    conclusions can be made. Io I I 1~ .. MATERIALS AND METHODS 1. Fasting Study. Pregnant and non-pregnant Dorset ewes weighing 50 to 55 kg were selected from...the uterus. Amniotic catheters and flow probe cables were exteriorized from the abdominal cavity through the maternal flank via a metal trocar and...cannula. Vascular catheters and EMG wires were passed tn the opposite direction using a second trocar and 4I cannula. I. ,° * -- - - -31- The fetal head

  10. Arachidonic acid metabolism and inhibition of cyclooxygenase in platelets from asthmatic subjects with aspirin intolerance. (United States)

    Bonne, C; Moneret-Vautrin, D A; Wayoff, M; Descharmes, A; Gazel, P; Legrand, A; Kalt, C


    Exaggerated inhibition of cyclooxygenase has been proposed as a mechanism of drug-induced bronchospasm in aspirin-intolerant patients. This study, using platelets, shows that inhibition of prostaglandin biosynthesis by aspirin is unmodified in patients when compared with healthy subjects. The ratio of cyclooxygenase:lipoxygenase products is similar in platelets from patients and control subjects. We conclude that the cyclooxygenase alteration observed in cells from the respiratory tract is not generalised to other cells such as platelets. We also propose that the major abnormality in NSAID-intolerant patients would affect receptivity to lipoxygenase products more than their biosynthesis.

  11. Oxidative modulation of transient potassium current by arachidonic acid in brain central neurons


    Angelova, Plamena


    Der neuronale Zelluntergang bei einer Vielzahl von Krankheiten des ZNS, wie z.B. Morbus Alzheimer (AD) und Temporallappenepilepsie (TLE), wird mit oxidativem Stress sowie Fehlfunktionen von Kaliumkanälen in Verbindung gebracht. In dieser Studie soll die selektive neuronale Sensitivität auf oxidativen Stress durch die Messung der oxidativen Modulation von Kaliumströmen untersucht werden. Dabei werden sternförmige Neuronen der zweiten Schicht des entorhinalen Kortex (EC) (bei AD bereits früh ge...

  12. Effects of some iridoids from plant origin on arachidonic acid metabolism in cellular systems. (United States)

    Bermejo Benito, P; Díaz Lanza, A M; Silván Sen, A M; De Santos Galindez, J; Fernandez Matellano, L; Sanz Gómez, A; Abad Martínez, M J


    Seven iridoid glycosides isolated from different extracts of Scrophularia scorodonia L., namely bartsioside, aucubin, harpagide, harpagoside, 8-acetylharpagide, scorodioside and scropolioside B, had been evaluated for their in vitro anti-inflammatory activity in cellular systems generating COX and LOX metabolites. Structure-activity relationships obtained from in vitro screening results were discussed. Most compounds assayed did not exhibit any significant effect on PGE2- and LTC4-release from calcium ionophore-stimulated mouse peritoneal macrophages. In the LTC4-assay, only aucubin showed a significant effect, with an IC50 value of 72 microM. Harpagoside and harpagide also inhibited release of LTC4, but neither effect reached statistical significance. The release of PGE2 by mouse peritoneal macrophages stimulated with calcium ionophore was inhibited by harpagoside and 8-acetylharpagide, but this effect is not statistically significant. However, most iridoids assayed showed a significant effect on TXB2-release from calcium ionophorestimulated human platelets, with inhibition percentages slightly lower than the reference drug ibuprofen. Only harpagide, scorodioside and scropolioside B had no significant effect on TXB2-release. Our results indicate that selective inhibition of the TX-synthase enzyme may be the primary target of action of most of these iridoids, and one of the mechanisms through which they exert their anti-inflammatory effects.

  13. Influence of mineral dusts on metabolism of arachidonic acid by alveolar macrophage

    Energy Technology Data Exchange (ETDEWEB)

    Demers, L.M.; Kuhn, D.C. [Pennsylvania State University, Hershey, PA (United States). Dept. of Pathology


    The alveolar macrophage (AM) responds to stimuli such as coal mine dust by releasing inflammatory mediators such as cytokines, growth factors, reactive oxygen species, and eicosanoids. In this report, the authors examined the effects of an antioxidant, vitamin E, on dust-induced synthesis of PGE(2) and TXB(2) in vitro and in vivo by AM obtained by bronchoalveolar lavage from rats. They also looked at the effects of the surface of silica particles on AM eicosanoid biosynthesis under conditions of calcination, a process that removes exposed hydroxyl groups from the surface of silica particles, thus reducing the likelihood of soluble hydroxyl radical formation. Treatment of AM with vitamin E in vivo and in vitro reduced the augmentation in eicosanoid production usually observed when AM are exposed to mine dusts. These results suggest that vitamin E may effectively reduce the inflammatory and fibrotic response produced by inhalation of mineral dust through an antioxidant mechanism. Silica that has been chemically altered by calcination was unable to activate AM eicosanoid production in vitro when compared to untreated, freshly fractured silica. These findings suggest that the mechanism by which dust particles can activate AM eicosanoid release may involve interaction of surface and/or soluble factors with the cell membrane. Taken together, these studies point to the involvement of Am eicosanoid production as part of the proinflammatory response of this cell to occupational inhalation of mineral dust.

  14. Ozone effects on mechanics and arachidonic acid metabolite concentrations in isolated rat lungs

    Energy Technology Data Exchange (ETDEWEB)

    Joad, J.P.; McDonald, R.J.; Giri, S.N.; Bric, J.M. (Univ. of California, Davis, CA (United States))


    In whole animals, ozone acutely impairs pulmonary function, an effect which may be mediated by eicosanoids. This study determined if the lung itself, separated from blood components and the CNS, responds to ozone with increased eicosanoid production and decreased function. Wistar rat lungs were placed in a negatively ventilated, buffer-perfused, isolated system, where they were exposed to filtered air or 1 ppm ozone for 3 hr. ozone increased lung resistance (P = 0.02) and decreased dynamic compliance (P = 0.003, multivariate ANOVA for repeated measures). Pulmonary artery pressure, lung weight/body weight, and cells in lung lavage (BALF) did not change. In the perfusate, ozone increased the concentration of 6-keto-PGF[sub 1[alpha

  15. Glutamate signalling and secretory phospholipase A2 modulate the release of arachidonic acid from neuronal membranes

    DEFF Research Database (Denmark)

    Rodriguez De Turco, Elena B; Jackson, Fannie R; DeCoster, Mark A


    and secretory PLA(2) (sPLA(2)) from bee venom (bv sPLA(2)) and Taipan snake venom (OS2) elicit synergy in inducing neuronal cell death. Low concentrations of sPLA(2) are selective ligands of cell-surface sPLA(2) receptors. We investigated which neuronal arachidonoyl phospholipids are targeted by glutamate...

  16. Arachidonic and oleic acid exert distinct effects on the DNA methylome

    DEFF Research Database (Denmark)

    Silva-Martínez, Guillermo A; Rodríguez-Ríos, Dalia; Alvarado-Caudillo, Yolanda


    embryonic fibroblasts. Comparisons with publicly available data were conducted by standard bioinformatics. AA and OA elicited a complex response marked by a general DNA hypermethylation and hypomethylation in the 1-200 μM range, respectively, with a maximal differential response at the 100 μM dose...

  17. Effect of steroid hormones on arachidonic acid metabolites of endothelial cells. (United States)

    Witter, F R; DiBlasi, M C


    The effect of estrogen, progesterone, testosterone, and hydrocortisone on prostacyclin, thromboxane, prostaglandin E, and prostaglandin F from cultured endothelial cells was investigated. No effect was found on prostacyclin, prostaglandin E, and prostaglandin F. Estrogen increased the release of thromboxane. The significance of this finding with regard to venous thrombolic events associated with estrogen use is discussed.

  18. EETs mediate cardioprotection of salvianolic acids through MAPK signaling pathway


    Shoubao Wang; Weiku Zhang; Xiaobin Pang; Li Li; Guorong He; Xiuying Yang; Lianhua Fang; Juntian Zhang; Guanhua Du


    Salvianolic acids, including salvianolic acid A (SAA) and salvianolic acid B (SAB), are the main water-soluble bioactive compounds isolated from the Chinese medicinal herb Danshen and have been shown to exert in vitro and in vivo cardiovascular protection. Recent studies suggest that epoxyeicosatrienoic acids (EETs), the primary cytochrome P450 2J (CYP2J) epoxygenase metabolites of arachidonic acid, are involved in the progression of ischemic injury in diverse organs. Here, we investigated th...

  19. Arginine-vasopressin stimulates the formation of phosphatidic acid in rat Leydig cells

    DEFF Research Database (Denmark)

    Nielsen, J.R.; Hansen, Harald S.; Jensen, B.


    Arginine-vasopressin (AVP) stimulated the formation of labelled phosphatidic acid (PA) in [C]arachidonic acid-prelabelled rat Leydig cells. After addition of 10 M AVP [C]arachidonoylphosphatidic acid reached a maximum within 2 min. The increase was dose-dependent (10-10 M). No change in labelling...

  20. Gestational age in relation to marine n-3 fatty acids in maternal erythrocytes

    DEFF Research Database (Denmark)

    Olsen, S.F.; Hansen, Harald S.; Sommer, S.;


    Gestation is longer in Faroese than Danish women, possibly because of the high intake of marine long-chain n-3 fatty acids that down regulates formation of prostaglandins from arachidonic acid. Polyunsaturated fatty acids were quantified in erythrocytes obtained within 2 days of delivery from...

  1. Changes in plasma and erythrocyte omega-6 and omega-3 fatty acids in response to intravenous supply of omega-3 fatty acids in patients with hepatic colorectal metastases


    Al-Taan, Omer; Stephenson, James A.; Spencer, Laura; Pollard, Cristina; West, Annette L; Philip C. Calder; Metcalfe, Matthew; Dennison, Ashley R.


    Background Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are functionally the most important omega-3 polyunsaturated fatty acids (PUFAs). Oral supply of these fatty acids increases their levels in plasma and cell membranes, often at the expense of the omega-6 PUFAs arachidonic acid (ARA) and linoleic acid. This results in an altered pattern of lipid mediator production to one which is less pro-inflammatory. We investigated whether short term intravenous supply of omega-3 PUFAs co...

  2. Essential fatty acid requirements of cats: pathology of essential fatty acid deficiency. (United States)

    MacDonald, M L; Anderson, B C; Rogers, Q R; Buffington, C A; Morris, J G


    The pathologic changes of essential fatty acid (EFA) deficiency were studied in specific-pathogen-free, domestic shorthair cats which were fed purified diets for 1.5 to 2.5 years. Cats fed an EFA-deficient diet exhibited signs of deficiency: severe fatty degeneration of the liver, excessive fat in the kidneys, dystrophic mineralization of the adrenal glands, degeneration of the testes, and hyperkeratosis of the skin. Minor clinical pathologic changes were consistent with liver damage. Fatty acid analyses of plasma lipids revealed low concentrations of linoleate and other n6-fatty acids, and high concentrations of n7- and n9-fatty acids, consistent with EFA deficiency. These signs of deficiency were prevented by including safflower seed oil in the diet at a concentration to supply linoleate at 6.7% of dietary energy. Therefore, linoleate is an EFA for the cat, despite negligible conversion of linoleate to arachidonate in cat liver. However, in cats fed a diet containing linoleate, but lacking arachidonate, there was mild mineralization of the kidneys, and the neutral fat content of the liver was slightly higher than that of cats fed a diet containing arachidonate and other long-chain polyunsaturated fatty acids. Also, 2 of the 19 cats fed arachidonate-deficient diets developed unusual inflammatory skin lesions. In cats fed a diet containing hydrogenated coconut oil, safflower seed oil, and chicken fat, fatty livers developed despite the presence of high levels of linoleate. The fatty livers appeared to result from a specific deleterious effect of the medium-chain triglycerides in hydrogenated coconut oil. Most of the organ pathologic changes of EFA deficiency in the cat can be prevented by feeding dietary linoleate. Linoleate meets the EFA requirement for functions which depend on proper membrane structure: growth, lipid transport, normal skin and coat condition, and maintenance of the epidermal permeability barrier. However, dietary arachidonate is required by the

  3. Developmentally dependent and different roles of fatty acids OMEGA-6 and OMEGA-3

    DEFF Research Database (Denmark)

    Mourek, J; Mourek, J


    The developmentally-dependent differences in the biological significances and effects of PUFA-OMEGA-6 (namely of arachidonic acid) and PUFA-OMEGA-3 (namely of docosahexaenoic acid) are discussed. The clinical results as well as developmental experiences are indicating a hypothesis of the evolution...... that created mutual relationship between those two substances (with immunological basis and following recuperation). The anti-inflammatory actions of PUFA-OMEGA-3 are the most visible (and significant) contrasts as compared with the large affects of namely arachidonic acid and its metabolites....

  4. Influence d'une microsporidiose à Thelohania contejeani sur le métabolisme des acides gras totaux, musculaires, hépatopancréatiques et hémolymphatiques chez l'Écrevisse Austropotamobius pallipes le reboulet, 1858. (United States)

    Kabre, G


    The fatty acids of muscular, hepatopancreatic, hemolymphatic of complete lipids of A. pallipes have a high degree of insaturation (40-50%). Palmitic, eicosapentenoïc, arachidonic, stearic, oleic acids are more than 90% of the acids. Into the parasited crayfishes, there is a decrease of the amount of the non-saturated acids and an increase of saturated acids rate.

  5. Inhibition of fatty acid synthesis in rat hepatocytes by exogenous polyunsaturated fatty acids is caused by lipid peroxidation

    DEFF Research Database (Denmark)

    Mikkelsen, L.; Hansen, Harald S.; Grunnet, N.


    by the peroxidized PUFA. Arachidonic acid and eicosapentaenoic acid showed a dose- and time-dependent cytotoxicity. Two other antioxidants: 50 µM a-tocopherol acid succinate and 1 µM N,N'-diphenyl-1,4-phenylenediamine, both proved more efficient than a-tocopherol phosphate. There was a significant correlation......Rat hepatocyte long-term cultures were utilized to investigate the impact of different polyunsaturated fatty acids (PUFA) on the insulin-induced de novo fatty acid synthesis in vitro. The addition of 0.5 mM albumin-complexed oleic, linoleic, columbinic, arachidonic, eicosapentaenoic...... or docosahexaenoic acid resulted in a marked suppression of fatty acid synthesis. By evaluation of cell viability (determined as the leakage of lactate dehydrogenase (LDH)) it turned our, that the antioxidant used (50 µM a-tocopherol phosphate) had a low antioxidant activity, resulting in cytotoxic effects...

  6. Effect of Long-Chain Polyunsaturated Fatty Acid Supplementation on Neurodevelopmental Outcome in Full-Term Infants

    NARCIS (Netherlands)

    Hadders-Algra, Mijna


    It takes more than 20 years before the human brain obtains its complex, adult configuration. Most dramatic developmental changes occur prenatally and early postnatally. During development, long-chain polyunsaturated fatty acids (LCPUFA) such as doxosahexaenoic acid (DHA) and arachidonic acid (AA) ar

  7. Interaction of fatty acid genotype and diet on changes in colonic fatty acids in a Mediterranean diet intervention study. (United States)

    Porenta, Shannon R; Ko, Yi-An; Gruber, Stephen B; Mukherjee, Bhramar; Baylin, Ana; Ren, Jianwei; Djuric, Zora


    A Mediterranean diet increases intakes of n-3 and n-9 fatty acids and lowers intake of n-6 fatty acids. This can impact colon cancer risk as n-6 fatty acids are metabolized to proinflammatory eicosanoids. The purpose of this study was to evaluate interactions of polymorphisms in the fatty acid desaturase (FADS) genes, FADS1 and FADS2, and changes in diet on fatty acid concentrations in serum and colon. A total of 108 individuals at increased risk of colon cancer were randomized to either a Mediterranean or a Healthy Eating diet. Fatty acids were measured in both serum and colonic mucosa at baseline and after six months. Each individual was genotyped for four single-nucleotide polymorphisms in the FADS gene cluster. Linear regression was used to evaluate the effects of diet, genotype, and the diet by genotype interaction on fatty acid concentrations in serum and colon. Genetic variation in the FADS genes was strongly associated with baseline serum arachidonic acid (n-6) but serum eicosapentaenoic acid (n-3) and colonic fatty acid concentrations were not significantly associated with genotype. After intervention, there was a significant diet by genotype interaction for arachidonic acid concentrations in colon. Subjects who had all major alleles for FADS1/2 and were following a Mediterranean diet had 16% lower arachidonic acid concentrations in the colon after six months of intervention than subjects following the Healthy Eating diet. These results indicate that FADS genotype could modify the effects of changes in dietary fat intakes on arachidonic acid concentrations in the colon.

  8. Long-chain polyunsaturated fatty acid status and early growth of low birth weight infants

    NARCIS (Netherlands)

    Woltil, HA; van Beusekom, CM; Schaafsma, A; Muskiet, FAJ; Okken, A


    We correlated arachidonic acid (AA) and docosahexaenoic acid (DHA) status with anthropometric measures and growth rates in a group of low birth weight infants (less than or equal to 2500 g; gestational ages 30-41 weeks; n = 143). AA and DHA status were measured in erythrocytes (RBC) and plasma chole

  9. Subchronic (13-week) oral toxicity study, preceded by an in utero exposure phase, with arachidonate-enriched triglyceride oil (SUNTGA40S) in rats. (United States)

    Lina, B A R; Wolterbeek, A P M; Suwa, Y; Fujikawa, S; Ishikura, Y; Tsuda, S; Dohnalek, M


    Polyunsaturated fatty acids (PUFAs), such as arachidonic acid (ARA) and docosahexaenoic acid (DHA) are natural constituents found in human milk, fish oil or egg yolk. Until recently, infant formulas, though providing the essential fatty acid precursors for these PUFAs, did not contain preformed ARA or DHA. In this study the safety of SUNTGA40S as source of ARA, not only for use in infant formulas but also for nutritional products or food supplements, was evaluated in a subchronic study in Wistar rats, preceded by a 4-week pretreatment period of parental (F(0)) rats and exposure of the F(0) dams throughout mating, gestation and lactation. SUNTGA40S was administered at dietary levels of 0.5%, 1.5% and 5% (wt/wt) adjusted with corn oil to 5.76% added fat. An additional group received 3.65% (wt/wt) SUNTGA40S in conjunction with 2.11% (wt/wt) high DHA Tuna oil, providing an ARA:DHA ratio of 2.7:1. High-fat and low-fat controls received basal diet with or without 5.76% corn-oil supplement. The content, stability and homogeneous distribution of the test substances in the diet were confirmed under study conditions. The administration of SUNTGA40S, with or without DHA oil, did not affect health, growth, fertility or reproductive performance of the parental rats, nor pup characteristics (condition, weight gain, viability, number per litter or sex ratio). In the subchronic study with the offspring (F(1)) rats, no significant differences were found in condition, neurobehavioural observations, ophthalmoscopy, growth, urinalysis or macroscopic and microscopic findings between the test groups and the low-fat or the high-fat controls. In males of the 5% SUNTGA40S and the SUNTGA40S/DHA group, red blood cell counts, haemoglobin concentration and packed cell volume were lower and reticulocytes were slightly higher than in the high-fat and low-fat control groups. Cholesterol, triglycerides and phospholipids in plasma were lower than in the high-fat controls in both sexes in the 5

  10. Growth and development of term infants fed with milk with long-chain polyunsaturated fatty acid supplementation

    Institute of Scientific and Technical Information of China (English)

    BEN Xiao-ming 贲晓明; ZHOU Xiao-yu 周晓玉; ZHAO Wei-hua 赵卫华; YU Wen-liang 喻文亮; PAN Wei 潘伟; ZHANG Wei-li 张伟利; WU Sheng-mei 吴圣楣; Christien M. Van Beusekom; Anne Schaafsma


    @@ Presently, there is growing interest in long-chain polyunsaturated fatty acids (LCPUFAs), which are considered a major determinant of growth, visual and neural development, and long-term health.1 Two groups of LCPUFAs have received special interest: homologues of linoleic acid (LA) of the n-6 series, which are precursors of arachidonic acid (AA), and homologues of α-linolenic acid (ALA) of the n-3 series, which are precursors of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

  11. The roles of long-chain polyunsaturated fatty acids in pregnancy, lactation and infancy: review of current knowledge and consensus recommendations

    DEFF Research Database (Denmark)

    Koletzko, Berthold; Lien, Eric; Agostoni, Carlo;


    This paper reviews current knowledge on the role of the long-chain polyunsaturated fatty acids (LC-PUFA), docosahexaenoic acid (DHA, C22:6n-3) and arachidonic acid (AA, 20:4n-6), in maternal and term infant nutrition as well as infant development. Consensus recommendations and practice guidelines...

  12. Dietary supplementation of essential fatty acids in larval pikeperch (Sander lucioperca); short and long term effects on stress tolerance and metabolic physiology

    DEFF Research Database (Denmark)

    Lund, Ivar; Skov, Peter Vilhelm; Hansen, Benni Winding


    The present study examined the effects of feeding pike perch larvae Artemia, enriched with either docosahexanoic acid (DHA), arachidonic acid (ARA), oleic acid (OA), olive oil (OO) or a commercial enrichment DHA Selco (DS) on tissue lipid deposition, stress tolerance, growth and development...

  13. [Study of the fatty acid components of the triglyceride fraction of the blood in normal and thalassemic subjects, using gas chromatography]. (United States)

    Gilli, G; Moiraghi Ruggenini, A; Nani, E; Bottura, G; Mastretta, L


    Thin layer chromatography was used to separate the triglyceridic fraction of plasma lipides in normal (19) and thalassaemic (15) subjects. Gas chromatographic analysis of the fraction was then carried out and the fatty acids represented were identified qualitatively and quantitatively. Statistically significant variations, specifically increase in arachidonic acid and reduction in palmitic and linoleic acids, were observed in the thalassaemic patients.

  14. Long-chain polyunsaturated fatty acids (LCPUFA) from genesis to senescence: the influence of LCPUFA on neural development, aging, and neurodegeneration.

    NARCIS (Netherlands)

    Janssen, C.I.F.; Kiliaan, A.J.


    Many clinical and animal studies demonstrate the importance of long-chain polyunsaturated fatty acids (LCPUFA) in neural development and neurodegeneration. This review will focus on involvement of LCPUFA from genesis to senescence. The LCPUFA docosahexaenoic acid and arachidonic acid are important c

  15. Mechanistic Perspectives of Maslinic Acid in Targeting Inflammation

    Directory of Open Access Journals (Sweden)

    Wei Hsum Yap


    Full Text Available Chronic inflammation drives the development of various pathological diseases such as rheumatoid arthritis, atherosclerosis, multiple sclerosis, and cancer. The arachidonic acid pathway represents one of the major mechanisms for inflammation. Prostaglandins (PGs are lipid products generated from arachidonic acid by the action of cyclooxygenase (COX enzymes and their activity is blocked by nonsteroidal anti-inflammatory drugs (NSAIDS. The use of natural compounds in regulation of COX activity/prostaglandins production is receiving increasing attention. In Mediterranean diet, olive oil and table olives contain significant dietary sources of maslinic acid. Maslinic acid is arising as a safe and novel natural pentacyclic triterpene which has protective effects against chronic inflammatory diseases in various in vivo and in vitro experimental models. Understanding the anti-inflammatory mechanism of maslinic acid is crucial for its development as a potential dietary nutraceutical. This review focuses on the mechanistic action of maslinic acid in regulating the inflammation pathways through modulation of the arachidonic acid metabolism including the nuclear factor-kappa B (NF-κB/COX-2 expression, upstream protein kinase signaling, and phospholipase A2 enzyme activity. Further investigations may provide insight into the mechanism of maslinic acid in regulating the molecular targets and their associated pathways in response to specific inflammatory stimuli.

  16. Different roles for non-receptor tyrosine kinases in arachidonate release induced by zymosan and Staphylococcus aureus in macrophages

    Directory of Open Access Journals (Sweden)

    Sundler Roger


    Full Text Available Abstract Background Yeast and bacteria elicit arachidonate release in macrophages, leading to the formation of leukotrienes and prostaglandins, important mediators of inflammation. Receptors recognising various microbes have been identified, but the signalling pathways are not entirely understood. Cytosolic phospholipase A2 is a major down-stream target and this enzyme is regulated by both phosphorylation and an increase in intracellular Ca2+. Potential signal components are MAP kinases, phosphatidylinositol 3-kinase and phospholipase Cγ2. The latter can undergo tyrosine phosphorylation, and Src family kinases might carry out this phosphorylation. Btk, a Tec family kinase, could also be important. Our aim was to further elucidate the role of Src family kinases and Btk. Methods Arachidonate release from murine peritoneal macrophages was measured by prior radiolabeling. Furthermore, immunoprecipitation and Western blotting were used to monitor changes in activity/phosphorylation of intermediate signal components. To determine the role of Src family kinases two different inhibitors with broad specificity (PP2 and the Src kinase inhibitor 1, SKI-1 were used as well as the Btk inhibitor LFM-A13. Results Arachidonate release initiated by either Staphylococcus aureus or yeast-derived zymosan beads was shown to depend on members of the Src kinase family as well as Btk. Src kinases were found to act upstream of Btk, phosphatidylinositol 3-kinase, phospholipase Cγ2 and the MAP kinases ERK and p38, thereby affecting all branches of the signalling investigated. In contrast, Btk was not involved in the activation of the MAP-kinases. Since the cytosolic phospholipase A2 in macrophages is regulated by both phosphorylation (via ERK and p38 and an increase in intracellular Ca2+, we propose that members of the Src kinase family are involved in both types of regulation, while the role of Btk may be restricted to the latter type. Conclusion Arachidonate release

  17. Ameliorative effects of polyunsaturated fatty acids against palmitic acid-induced insulin resistance in L6 skeletal muscle cells

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    Sawada Keisuke


    Full Text Available Abstract Background Fatty acid-induced insulin resistance and impaired glucose uptake activity in muscle cells are fundamental events in the development of type 2 diabetes and hyperglycemia. There is an increasing demand for compounds including drugs and functional foods that can prevent myocellular insulin resistance. Methods In this study, we established a high-throughput assay to screen for compounds that can improve myocellular insulin resistance, which was based on a previously reported non-radioisotope 2-deoxyglucose (2DG uptake assay. Insulin-resistant muscle cells were prepared by treating rat L6 skeletal muscle cells with 750 μM palmitic acid for 14 h. Using the established assay, the impacts of several fatty acids on myocellular insulin resistance were determined. Results In normal L6 cells, treatment with saturated palmitic or stearic acid alone decreased 2DG uptake, whereas unsaturated fatty acids did not. Moreover, co-treatment with oleic acid canceled the palmitic acid-induced decrease in 2DG uptake activity. Using the developed assay with palmitic acid-induced insulin-resistant L6 cells, we determined the effects of other unsaturated fatty acids. We found that arachidonic, eicosapentaenoic and docosahexaenoic acids improved palmitic acid-decreased 2DG uptake at lower concentrations than the other unsaturated fatty acids, including oleic acid, as 10 μM arachidonic acid showed similar effects to 750 μM oleic acid. Conclusions We have found that polyunsaturated fatty acids, in particular arachidonic and eicosapentaenoic acids prevent palmitic acid-induced myocellular insulin resistance.

  18. High expression of arachidonate 15-lipoxygenase and proinflammatory markers in human ischemic heart tissue

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    Magnusson, Lisa U.; Lundqvist, Annika [Sahlgrenska Center for Cardiovascular and Metabolic Research, Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg (Sweden); Asp, Julia [Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg (Sweden); Synnergren, Jane [Systems Biology Research Center, School of Life Sciences, University of Skoevde, Skoevde (Sweden); Johansson, Cecilia Thalen [Sahlgrenska Center for Cardiovascular and Metabolic Research, Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg (Sweden); Palmqvist, Lars [Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg (Sweden); Jeppsson, Anders [Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, Gothenburg (Sweden); Hulten, Lillemor Mattsson, E-mail: [Sahlgrenska Center for Cardiovascular and Metabolic Research, Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg (Sweden)


    Highlights: Black-Right-Pointing-Pointer We found a 17-fold upregulation of ALOX15 in the ischemic heart. Black-Right-Pointing-Pointer Incubation of human muscle cells in hypoxia showed a 22-fold upregulation of ALOX15. Black-Right-Pointing-Pointer We observed increased levels of proinflammatory markers in ischemic heart tissue. Black-Right-Pointing-Pointer Suggesting a link between ischemia and inflammation in ischemic heart biopsies. -- Abstract: A common feature of the ischemic heart and atherosclerotic plaques is the presence of hypoxia (insufficient levels of oxygen in the tissue). Hypoxia has pronounced effects on almost every aspect of cell physiology, and the nuclear transcription factor hypoxia inducible factor-1{alpha} (HIF-1{alpha}) regulates adaptive responses to low concentrations of oxygen in mammalian cells. In our recent work, we observed that hypoxia increases the proinflammatory enzyme arachidonate 15-lipoxygenase (ALOX15B) in human carotid plaques. ALOX15 has recently been shown to be present in the human myocardium, but the effect of ischemia on its expression has not been investigated. Here we test the hypothesis that ischemia of the heart leads to increased expression of ALOX15, and found an almost 2-fold increase in HIF-1{alpha} mRNA expression and a 17-fold upregulation of ALOX15 mRNA expression in the ischemic heart biopsies from patients undergoing coronary bypass surgery compared with non ischemic heart tissue. To investigate the effect of low oxygen concentration on ALOX15 we incubated human vascular muscle cells in hypoxia and showed that expression of ALOX15 increased 22-fold compared with cells incubated in normoxic conditions. We also observed increased mRNA levels of proinflammatory markers in ischemic heart tissue compared with non-ischemic controls. In summary, we demonstrate increased ALOX15 in human ischemic heart biopsies. Furthermore we demonstrate that hypoxia increases ALOX15 in human muscle cells. Our results yield

  19. Fatty acid composition of red blood cell membranes and risk of squamous cell carcinoma of the skin. (United States)

    Harris, Robin B; Foote, Janet A; Hakim, Iman A; Bronson, Dan L; Alberts, David S


    Differential effects of fatty acids on carcinogenesis suggest that fatty acid composition is important in tumor development. Arachidonic acid and its metabolites elicit inflammation and promote tumor formation in mouse skin. Inhibitors of the arachidonic cascade inhibit tumor incidence. A population-based case control study in Southeastern Arizona tested the hypothesis that lower levels of arachidonic acid in RBC membranes were associated with decreased risk of skin squamous cell carcinoma (SCC; n = 335 SCC cases and 321 controls). Extracted and esterified RBC fatty acids were analyzed using capillary gas chromatography. Individual peaks for 14 fatty acids were measured as a percentage of total fatty acids. Logistic regression was used to estimate odds ratios (OR), adjusting for SCC risk factors (age, gender, actinic keratosis history, freckling, and tanning ability). Increased levels of arachidonic acid in RBC membranes were associated with increased risk of SCC [odds ratio (OR), 1.08 per mg/100 mL change; 95% confidence interval (95% CI), 1.02-1.15] and this association remained when controls with actinic keratosis precursor lesions were excluded. SCC risk was highest among the upper quartile of arachidonic acid (OR, 2.38; 95% CI, 1.37-4.12). In contrast, increasing proportions of palmitic acid (OR, 0.94; 95% CI, 0.89-1.00) and palmitoleicacid (OR, 0.49; 95% CI, 0.30-0.81) were associated with reduced SCC risk. More studies are needed to elucidate the function of RBC fatty acids so that recommendations can be made to alter the human diet for cancer prevention.

  20. A plasma membrane-targeted cytosolic domain of STIM1 selectively activates ARC channels, an arachidonate-regulated store-independent Orai channel. (United States)

    Thompson, Jill L; Shuttleworth, Trevor J


    The Orai family of calcium channels includes the store-operated CRAC channels and store-independent, arachidonic acid (AA)-regulated ARC channels. Both depend on STIM1 for their activation but, whereas CRAC channel activation involves sensing the depletion of intracellular calcium stores via a luminal N terminal EF-hand of STIM1 in the endoplasmic reticulum (ER) membrane, ARC channels are exclusively activated by the pool of STIM1 that constitutively resides in the plasma membrane (PM). Here, the EF-hand is extracellular and unlikely to ever lose its bound calcium, suggesting that STIM1-dependent activation of ARC channels is very different from that of CRAC channels. We now show that attachment of the cytosolic portion of STIM1 to the inner face of the PM via an N terminal Lck-domain sequence is sufficient to enable normal AA-dependent activation of ARC channels, while failing to allow activation of store-operated CRAC channels. Introduction of a point mutation within the Lck-domain resulted in the loss of both PM localization and ARC channel activation. Reversing the orientation of the PM-anchored STIM1 C terminus via a C-terminal CAAX-box fails to support either CRAC or ARC channel activation. Finally, the Lck-anchored STIM1 C-terminal domain also enabled the exclusive activation of the ARC channels following physiological agonist addition. These data demonstrate that simple tethering of the cytosolic C-terminal domain of STIM1 to the inner face of the PM is sufficient to allow the full, normal and exclusive activation of ARC channels, and that the N-terminal regions of STIM1 (including the EF-hand domain) play no significant role in this activation.

  1. Release of arachidonic and linoleic acid metabolites in skin organ cultures as characteristics of in vitro skin irritancy

    NARCIS (Netherlands)

    Sandt, J.J.M. van de; Maas, W.J.M.; Doornink, P.C.; Rutten, A.A.J.J.L.


    In vitro techniques make a major contribution to the development of alternatives to the in vivo 'Draize' skin irritation test, and the development of sensitive and generally applicable in vitro endpoints of cutaneous toxicity is an area of intensive research. To investigate in vitro characteristics

  2. Calcium ionophore (A-23187 induced peritoneal eicosanoid biosynthesis: a rapid method to evaluate inhibitors of arachidonic acid metabolism in vivo

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    T. S. Rao


    Full Text Available The present investigation characterizes calcium ionophore (A-23187 induced peritoneal eicosanoid biosynthesis in the rat. Intraperitoneal injection of A-23187 (20 μg/rat stimulated marked biosynthesis of 6-keto-PGF1α (6-KPA, TxB2, LTC4 and LTB4, with no detectable changes on levels of PGE2. Levels of all eicosanoids decreased rapidly after a peak which was seen as early as 5 min. Enzyme markers of cellular contents of neutrophils and mononuclear cells, MPO and NAG respectively, decreased rapidly after ionophore injection; this was followed by increases after 60 min. Indomethacin, a selective cyclooxygenase inhibitor, and zileuton and ICI D-2138, two selective 5-lipoxygenase inhibitors attenuated prostaglandin and leukotriene pathways respectively. Oral administration of zileuton (20 mg/kg, p.o. inhibited LTB4 biosynthesis for up to 6 h suggesting a long duration of pharmacological activity in the rats consistent with its longer half-life. The rapid onset and the magnitude of increases in levels of eicosanoids render the ionophore induced peritoneal eicosanoid biosynthesis a useful model to evaluate pharmacological profiles of inhibitors of eicosanoid pathways in vivo.

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



    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 DH...

  4. The function of very long chain polyunsaturated fatty acids in the pineal gland. (United States)

    Catalá, Angel


    The mammalian pineal gland is a prominent secretory organ with a high metabolic activity. Melatonin (N-acetyl-5-methoxytryptamine), the main secretory product of the pineal gland, efficiently scavenges both the hydroxyl and peroxyl radicals counteracting lipid peroxidation in biological membranes. Approximately 25% of the total fatty acids present in the rat pineal lipids are represented by arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3). These very long chain polyunsaturated fatty acids play important roles in the pineal gland. In addition to the production of melatonin, the mammalian pineal gland is able of convert these polyunsaturated fatty acids into bioactive lipid mediators. Lipoxygenation is the principal lipoxygenase (LOX) activity observed in the rat pineal gland. Lipoxygenation in the pineal gland is exceptional because no other brain regions express significant LOX activities under normal physiological conditions. The rat pineal gland expresses both 12- and 15-lipoxygenase (LOX) activities, producing 12- and 15-hydroperoxyeicosatetraenoic acid (12- and 15-HpETE) from arachidonic acid and 14- and 17-hydroxydocosahexaenoic acid (14- and 17-HdoHE) from docosahexaenoic acid, respectively. The rat pineal also produces hepoxilins via LOX pathways. The hepoxilins are bioactive epoxy-hydroxy products of the arachidonic acid metabolism via the 12S-lipoxygenase (12S-LOX) pathway. The two key pineal biochemical functions, lipoxygenation and melatonin synthesis, may be synergistically regulated by the status of n-3 essential fatty acids.

  5. Trans isomeric octadecenoic acids are related inversely to arachidonic acid and DHA and positively related to mead acid in umbilical vessel wall lipids

    NARCIS (Netherlands)

    Decsi, T; Boehm, G; Tjoonk, HMR; Molnar, S; Dijck-Brouwer, DAJ; Hadders-Algra, M; Martini, IA; Muskiet, FAJ; Boersma, ER


    Long-chain PUFA play an important role in early human neurodevelopment. Significant inverse correlations were reported between values of trans isomeric and long-chain PUFA in plasma lipids of preterm infants and children aged 1-15 yr as well as in venous cord blood lipids of full-term infants. Here

  6. Les rôles physiologiques majeurs exercés par les acides gras polyinsaturés (AGPI)


    Guesnet Philippe; Alessandri Jean-Marc; Astorg Pierre; Pifferi Fabien; Lavialle Monique


    Polyunsaturated fatty acids (PUFAs) are essential nutrients for mammals and the human species, and belong to either of two distinct and not interconvertible series, omega 6 and omega 3. The metabolic precursors of these two series, linoleic and α-linolenic acids respectively, are the dietary essential fatty acids. These two fatty acids, once absorbed, lead to the specific synthesis and incorporation in practically all cell membranes of long-chain active PUFA derivatives such as arachidonic ac...

  7. Effects of Fatty Acids on Intracellular [Ca2+], Mitochondrial Uncoupling and Apoptosis in Rat Pachytene Spermatocytes and Round Spermatids.

    Directory of Open Access Journals (Sweden)

    Joaquín Paillamanque

    Full Text Available The aim of this work was to explore the ability of free arachidonic acid, palmitic acid and the unsaturated fatty acids oleic acid and docosahexaenoic acid to modify calcium homeostasis and mitochondrial function in rat pachytene spermatocytes and round spermatids. In contrast to palmitic acid, unsaturated fatty acids produced significant increases in intracellular calcium concentrations ([Ca2+]i in both cell types. Increases were fatty acid specific, dose-dependent and different for each cell type. The arachidonic acid effects on [Ca2+]i were higher in spermatids than in spermatocytes and persisted when residual extracellular Ca2+ was chelated by EGTA, indicating that the increase in [Ca2+]i originated from release of intracellular calcium stores. At the concentrations required for these increases, unsaturated fatty acids produced no significant changes in the plasma membrane potential of or non-specific permeability in spermatogenic cells. For the case of arachidonic acid, the [Ca2+]i increases were not caused by its metabolic conversion to eicosanoids or anandamide; thus we attribute this effect to the fatty acid itself. As estimated with fluorescent probes, unsaturated fatty acids did not affect the intracellular pH but were able to induce a progressive decrease in the mitochondrial membrane potential. The association of this decrease with reduced reactive oxygen species (ROS production strongly suggests that unsaturated fatty acids induced mitochondrial uncoupling. This effect was stronger in spermatids than in spermatocytes. As a late event, arachidonic acid induced caspase 3 activation in a dose-dependent manner both in the absence and presence of external Ca2+. The concurrent but differential effects of unsaturated fatty acids on [Ca2+]i and mitochondrial functions are additional manifestations of the metabolic changes that germ cells undergo during their differentiation.

  8. [Phospholipid and fatty acid content of the blood of sheep infected with the nematode Dictyocaulus filaria]. (United States)

    Kuchbaev, A E; Bastarbekova, G M


    The results of analysis of phospholipids (PL) and fatty acid content in the blood of sheep infected with the nematodes Dictyocaulus filaria are displayed. A significant increase of lysophosphatidylcholine and arachidonic acid as well as a decrease of docozagexaenic acid in PL of infected sheep have been recorded. That points out to structural and functional disorders of cellular membranes during the infection. These disorder could be used as a metabolic criterion to estimate the relationships within the host-parasite system examined.

  9. Long-chain n-3 fatty acids and inflammation: potential application in surgical and trauma patients

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    Calder P.C.


    Full Text Available Lipids used in nutritional support of surgical or critically ill patients have been based on soybean oil, which is rich in the n-6 fatty acid linoleic acid (18:2n-6. Linoleic acid is the precursor of arachidonic acid (20:4n-6. In turn, arachidonic acid in cell membrane phospholipids is the substrate for the synthesis of a range of biologically active compounds (eicosanoids including prostaglandins, thromboxanes, and leukotrienes. These compounds can act as mediators in their own right and can also act as regulators of other processes, such as platelet aggregation, blood clotting, smooth muscle contraction, leukocyte chemotaxis, inflammatory cytokine production, and immune function. There is a view that an excess of n-6 fatty acids should be avoided since this could contribute to a state where physiological processes become dysregulated. One alternative is the use of fish oil. The rationale of this latter approach is that fish oil contains long chain n-3 fatty acids, such as eicosapentaenoic acid. When fish oil is provided, eicosapentaenoic acid is incorporated into cell membrane phospholipids, partly at the expense of arachidonic acid. Thus, there is less arachidonic acid available for eicosanoid synthesis. Hence, fish oil decreases production of prostaglandins like PGE2 and of leukotrienes like LTB4. Thus, n-3 fatty acids can potentially reduce platelet aggregation, blood clotting, smooth muscle contraction, and leukocyte chemotaxis, and can modulate inflammatory cytokine production and immune function. These effects have been demonstrated in cell culture, animal feeding and healthy volunteer studies. Fish oil decreases the host metabolic response and improves survival to endotoxin in laboratory animals. Recently clinical studies performed in various patient groups have indicated benefit from this approach.

  10. Lipid malnutrition of patients with liver cirrhosis: effect of low intake of dietary lipid on plasma fatty acid composition.

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    Full Text Available The plasma fatty acid composition of cirrhotic patients and their dietary intake of fatty acids were determined. Significantly lower plasma arachidonic, docosahexaenoic, dihomo-gamma-linolenic and eicosapentaenoic acid levels were observed in cirrhotic patients than in healthy controls. A remarkably low dietary intake of polyunsaturated fatty acids supplied from fish, vegetable oil and pulses was shown in cirrhotic patients. Positive correlations were observed between plasma arachidonic acid concentrations and clearance rate of indocyanine green (KICG (r = 0.826, p less than 0.05 and between dihomo-gamma-linolenic acid levels and cholinesterase activities (r = 0.841, p less than 0.05. From these results, we conclude that a supply of polyunsaturated fatty acids is necessary for the nutritional treatment of patients with liver cirrhosis.

  11. Inhibitors of arachidonate-regulated calcium channel signaling suppress triggered activity induced by the late sodium current. (United States)

    Wolkowicz, Paul; Umeda, Patrick K; Sharifov, Oleg F; White, C Roger; Huang, Jian; Mahtani, Harry; Urthaler, Ferdinand


    Disturbances in myocyte calcium homeostasis are hypothesized to be one cause for cardiac arrhythmia. The full development of this hypothesis requires (i) the identification of all sources of arrhythmogenic calcium and (ii) an understanding of the mechanism(s) through which calcium initiates arrhythmia. To these ends we superfused rat left atria with the late sodium current activator type II Anemonia sulcata toxin (ATXII). This toxin prolonged atrial action potentials, induced early afterdepolarization, and provoked triggered activity. The calmodulin-dependent protein kinase II (CaMKII) inhibitor KN-93 (N-[2-[[[3-(4-chlorophenyl)-2-propenyl]methylamino]methyl]phenyl]-N-(2-hydroxyethyl)-4-methoxybenzenesulphon-amide) suppressed ATXII triggered activity but its inactive congener KN-92 (2-[N-(4-methoxy benzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine) did not. Neither drug affected normal atrial contractility. Calcium entry via L-type channels or calcium leakage from sarcoplasmic reticulum stores are not critical for this type of ectopy as neither verapamil ((RS)-2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl]-(methyl)amino}-2-prop-2-ylpentanenitrile) nor ryanodine affected ATXII triggered activity. By contrast, inhibitors of the voltage independent arachidonate-regulated calcium (ARC) channel and the store-operated calcium channel specifically suppressed ATXII triggered activity without normalizing action potentials or affecting atrial contractility. Inhibitors of cytosolic calcium-dependent phospholipase A2 also suppressed triggered activity suggesting that this lipase, which generates free arachidonate, plays a key role in ATXII ectopy. Thus, increased left atrial late sodium current appears to activate atrial Orai-linked ARC and store operated calcium channels, and these voltage-independent channels may be unexpected sources for the arrhythmogenic calcium that underlies triggered activity.

  12. Enhancement of neutrophil-mediated killing of Plasmodium falciparum asexual blood forms by fatty acids: importance of fatty acid structure. (United States)

    Kumaratilake, L M; Ferrante, A; Robinson, B S; Jaeger, T; Poulos, A


    Effects of fatty acids on human neutrophil-mediated killing of Plasmodium falciparum asexual blood forms were investigated by using a quantitative radiometric assay. The results showed that the antiparasitic activity of neutrophils can be greatly increased (>threefold) by short-term treatment with fatty acids with 20 to 24 carbon atoms and at least three double bonds. In particular, the n-3 polyenoic fatty acids, eicosapentaenoic and docosahexaenoic acids, and the n-6 fatty acid, arachidonic acid, significantly enhanced neutrophil antiparasitic activity. This effect was >1.5-fold higher than that induced by an optical concentration of the known agonist cytokine tumor necrosis factor alpha (TNF-alpha). At suboptimal concentrations, the combination of arachidonic acid and TNF-alpha caused a synergistic increase in neutrophil-mediated parasite killing. The fatty acid-induced effect was independent of the availability of serum opsonins but dependent on the structure of the fatty acids. The length of the carbon chain, degree of unsaturation, and availability of a free carboxyl group were important determinants of fatty acid activity. The fatty acids which increased neutrophil-mediated killing primed the enhanced superoxide radical generation of neutrophils in response to P. falciparum as detected by chemiluminescence. Scavengers of oxygen radicals significantly reduced the fatty acid-enhanced parasite killing, but cyclooxygenase and lipoxygenase inhibitors had no effect. These findings have identified a new class of immunoenhancers that could be exploited to increase resistance against Plasmodium species.

  13. Decreased Polyunsaturated Fatty Acid Content Contributes to Increased Survival in Human Colon Cancer

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    Manuela Oraldi


    Full Text Available Among diet components, some fatty acids are known to affect several stages of colon carcinogenesis, whereas others are probably helpful in preventing tumors. In light of this, our aim was to determine the composition of fatty acids and the possible correlation with apoptosis in human colon carcinoma specimens at different Duke's stages and to evaluate the effect of enriching human colon cancer cell line with the possible reduced fatty acid(s. Specimens of carcinoma were compared with the corresponding non-neoplastic mucosa: a significant decrease of arachidonic acid, PPARα, Bad, and Bax and a significant increase of COX-2, Bcl-2, and pBad were found. The importance of arachidonic acid in apoptosis was demonstrated by enriching a Caco-2 cell line with this fatty acid. It induced apoptosis in a dose- and time-dependent manner via induction of PPARα that, in turn, decreased COX-2. In conclusion, the reduced content of arachidonic acid is likely related to carcinogenic process decreasing the susceptibility of cancer cells to apoptosis.

  14. Early intake of long-chain polyunsaturated fatty acids preserves brain structure and function in diet-induced obesity

    NARCIS (Netherlands)

    Arnoldussen, I.A.C.; Zerbi, V.; Wiesmann, M.; Noordman, R.H.J.; Bolijn, S.; Mutsaers, M.P.C.; Dederen, P.J.W.C.; Kleemann, R.; Kooistra, T.; Tol, E.A.F. van; Gross, G.; Schoemaker, M.H.; Wieling, P.Y.; Kilian, A.


    orldwide, the incidence of obesity is increasing at an alarming rate, and the number of children with obesity is especially worrisome. These developments raise concerns about the physical, psychosocial and cognitive consequences of obesity. It was shown that early dietary intake of arachidonic acid

  15. Role and significance of polyunsaturated fatty acids in nutrition in prevention and treatment of atherosclerosis

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    Ristić Vanja I.


    Full Text Available Introduction Hyperlipoproteinemia is a key factor in development of atherosclerosis, whereas regression of atherosclerosis mostly depends on decreasing the plasma level of total and LDL-cholesterol. Many studies have reported the hypocholesterolemic effect of linolenic acid. Types of polyunsaturated fatty acids (PUFA Linoleic and α-linolenic acids are essential fatty acids. The main sources of linoleic acid are vegetable seeds and of α-linolenic acid - green parts of plants. α-linolenic acid is converted to eicosapentaenoic and docosahexaenoic acid. Linoleic acid is converted into arachidonic acid competing with eicosapentaenoic acid in the starting point for synthesis of eicosanoids, which are strong regulators of cell functions and as such, very important in physiology and pathophysiology of cardiovascular system. Eicosanoids derived from eicosapentaenoic acid have different biological properties in regard to those derived from arachidonic acid, i.e. their global effects result in decreased vasoconstriction platelet aggregation and leukocyte toxicity. Role and significant of PUFA The n-6 to n-3 ratio of polyunsaturated fatty acids in the food is very important, and an optimal ratio 4 to 1 in diet is a major issue. Traditional western diets present absolute or relative deficiency of n-3 polyunsaturated fatty acids, and a ratio 15-20 to 1. In our diet fish and fish oil are sources of eicosapentaenoic and docosahexaenoic acid. Refined and processed vegetable oils change the nature of polyunsaturated fatty acids and obtained derivates have atherogenic properties.

  16. Exogenous arachidonate restores the dimethoate-induced inhibition of steroidogenesis in rat interstitial cells. (United States)

    Astiz, Mariana; Hurtado de Catalfo, Graciela; de Alaniz, María J T; Marra, Carlos Alberto


    The present work studies the potential restorative effect of polyunsaturated fatty acids (PUFA, 5 μM/24 h) on the dimethoate (DMT)-induced inhibition of testosterone biosynthesis in Leydig cells isolated from rat testes. Various fatty acids (FA) from the n-6 (18:2, 20:3, 20:4, 22:4 and 22:5) and n-3 (18.3, 20:5, 22:5, 22:6) series were assayed in Leydig cells, alone (as delipidated BSA complexes) and in combination with DMT (1 ppm). The n-6 FA stimulated lipid peroxidation (LPO) and inhibited the activities of steroidogenic enzymes (3β- and 17β-hydroxysteroid dehydrogenases). The n-3 FA exerted an anti-oxidant effect, decreasing the production of thiobarbituric-acid reactive substances (TBARS) and inhibiting phospholipase A(2) activity. The biosynthesis of testosterone in DMT-treated cultures was completely normalized by ARA (20:4n-6) and partially restored by the addition of 20:3n-6, increasing ARA content inside the mitochondria. The other FA assayed failed to restore androgenesis. COX-2 protein and prostaglandin F2α and E2 production were stimulated by 20:3n-6, ARA, 18:3n-3 and 20:5 n-3. COX-2 protein decreased upon addition of 22:5n-3 and 22:6n-3. StAR protein was increased by ARA and partially increased by 20:3n-6, likely due to its metabolic conversion into ARA. Both FA increased the mitochondrial cholesterol pool available for testosterone biosynthesis. The rate of androgenesis is likely the result of various regulatory factors acting concomitantly on the physiology of Leydig cells.

  17. Can essential fatty acids reduce the burden of disease(s?

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    Das Undurti N


    Full Text Available Abstract Coronary heart disease, stroke, diabetes mellitus, hypertension, cancer, depression schizophrenia, Alzheimer's disease, and collagen vascular diseases are low-grade systemic inflammatory conditions that are a severe burden on health care resources. Essential fatty acids (EFAs and their metabolites: eicosapentaenoic acid (EPA, docosahexaenoic acid (DHA, gamma-linolenic acid (GLA, dihomo-gamma-linolenic acid (DGLA, and arachidonic acid (AA and their products: prostaglandin E1, prostacyclin, lipoxins, resolvins, and protectins suppress inflammation, augment healing, and are of benefit in the prevention and management of these conditions. Hence, supplementation of EFAs could reduce burden of these disease(s.

  18. Autistic children exhibit decreased levels of essential Fatty acids in red blood cells. (United States)

    Brigandi, Sarah A; Shao, Hong; Qian, Steven Y; Shen, Yiping; Wu, Bai-Lin; Kang, Jing X


    Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFA) are essential nutrients for brain development and function. However, whether or not the levels of these fatty acids are altered in individuals with autism remains debatable. In this study, we compared the fatty acid contents between 121 autistic patients and 110 non-autistic, non-developmentally delayed controls, aged 3-17. Analysis of the fatty acid composition of red blood cell (RBC) membrane phospholipids showed that the percentage of total PUFA was lower in autistic patients than in controls; levels of n-6 arachidonic acid (AA) and n-3 docosahexaenoic acid (DHA) were particularly decreased (pautism.

  19. Constant Fiber Number During Skeletal Muscle Atrophy and Modified Arachidonate Metabolism During Hypertrophy (United States)

    Templeton, G.


    A previously documented shift from Type I to IIA predominance of the soleus muscle during rat suspension was further investigated to determine if this shift was by selective reduction of a single fiber type, simultaneous reduction and formation of fibers with different fiber types, or a transformation of fiber type by individual fibers. By partial acid digestion and dissection, average total soleus fiber number was found to be 3022 + or - 80 (SE) and 3008 + or - 64 before and after four-week suspension (n=12). Another area of current research was based on previous studies which indicate that prostaglandins are biosynthesized by skeletal muscle and evoke protein synthesis and degradation.

  20. Influence of Thermal Neutrons on Fatty Acids with a Mesomorphic Behavior (United States)

    Honciuc, M.; Slavnicu, E.

    The paper describes the influence of thermal neutron irradiation on the smectic liquid crystal (SLC) properties of fatty acids: lauric, archydic, elaidic and arachidonic. These fatty acids are precursors or constituents of biological membranes. Microstructural aspects and electric measurements of the dependence of current intensity through the sample on the applied external voltage I=I(U) are presented. An outline of a thermodynamic model in good agreement with the experiments is also given.

  1. Health Implications of High Dietary Omega-6 Polyunsaturated Fatty Acids


    Patterson, E.; Wall, R.; Fitzgerald, G. F.; R. P. Ross; Stanton, C.


    Omega-6 (n-6) polyunsaturated fatty acids (PUFA) (e.g., arachidonic acid (AA)) and omega-3 (n-3) PUFA (e.g., eicosapentaenoic acid (EPA)) are precursors to potent lipid mediator signalling molecules, termed “eicosanoids,” which have important roles in the regulation of inflammation. In general, eicosanoids derived from n-6 PUFA are proinflammatory while eicosanoids derived from n-3 PUFA are anti-inflammatory. Dietary changes over the past few decades in the intake of n-6 and n-3 PUFA show str...

  2. Mechanisms involved in the differential reduction of omega-3 and omega-6 highly unsaturated fatty acids by structural heart disease resulting in "HUFA deficiency". (United States)

    Rupp, Heinz; Rupp, Thomas P; Alter, Peter; Maisch, Bernhard


    The causes of reduced levels of omega-3 and omega-6 highly unsaturated fatty acids ("HUFA deficiency") in heart failure remain unresolved. HUFA profiles were examined in the serum of 331 patients with failing versus nonfailing heart disease. Arachidonic acid was positively correlated (P acid (EPA) (r = 0.40) and docosahexaenoic acid (DHA) (r = 0.53) and negatively with palmitic (r = 0.42), palmitoleic (r = 0.38), and oleic acid (r = 0.48). Delta-5 desaturase activity was reduced (P heart failure patients with low ejection fraction, dilatation, increased wall stress, and reduced heart rate variability (SDNN). In these patients, the reduced (P acid (P = 0.05) arose from separate influences involving reduced cardiac contractility (arachidonic acid and palmitic acid predicted by ejection fraction) and chamber dilatation (DHA and oleic acid predicted by end-diastolic diameter). A low DHA (0.2%-0.9% versus 1.4%-3.1%) was associated (P fatty acid oxidation (CPT-1 inhibition). Based on administration of omega-3 HUFA (OMACOR), dilatation is identified as a target for 1-2 g omega-3 HUFA·day(-1). Interventions for reduced arachidonic acid remain to be explored.

  3. Levels of prostaglandins and arachidonic acid in UV-B irradiated human skin before and after topical application of benzyl-2,5-diacetoxybenzoate, a salicylic acid derivative

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    Barr, R.M.; Black, A.K.; Mallet, A.I.; Greaves, M.W.


    Benzyl-2,5-diacetoxybenzoate (BDAB) was tested for anti-inflammatory activity on experimentally inflamed skin. Human abdominal skin was irradiated with three minimal erythema doses of UV-B (290-320nm) radiation to give a maximum erythema at 24 hours with an associated rise in PGE2 and PGF2 alpha levels measured by gas chromatography-mass spectrometry. Topical application of a 1% w/w preparation of BDAB neither decreased the evoked erythema nor diminished the rise in PGE2 and PGF2 alpha concentrations. BDAB, applied topically, was judged to be ineffectual as an anti-inflammatory agent in UV-B erythema.

  4. Exploratory investigation reveals parallel alteration of plasma fatty acids and eicosanoids in coronary artery disease patients. (United States)

    Xu, Yong-Jiang; Ho, Wanxing Eugene; Xu, Fengguo; Wen, Tao; Ong, Choon Nam


    Fatty acids and eicosanoids are two important classes of signaling lipid molecules involved in the pathogenesis of cardiovascular diseases. To investigate the physiological functions and interplay between fatty acids and eicosanoids in coronary artery disease (CAD) patients, we developed an analytical approach for parallel quantitative analysis of plasma fatty acids and eicosanoids, using gas chromatography-tandem mass spectrometry (GC-MS/MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). In this study, 26 fatty acids and 12 eicosanoids were confidently detected in 12 patients with confirmed coronary artery disease and 11 healthy subjects. Pattern recognition analysis (principal components analysis, orthogonal partial least-square discriminate analysis, and hierarchical clustering analysis) demonstrated that the plasma lipid profile of fatty acids and eicosanoids enabled robust discrimination of CAD patients versus healthy subjects. Significant differences in six fatty acids and five eicosanoids were noted among CAD patients and healthy subjects. The development of cardiovascular disease-induced metabolic change of fatty acids and eicosanoids, such as eicosapentaenoic acid, docosahexaenoic acid, arachidonic acid, hydroxyeicosatetraenoic acids and hydroxyoctadecadienoic acid, were consistent with previous isolated observations. Moderate-strong correlations between three plasma fatty acids and three eicosanoids from arachidonic acid metabolism were also observed. In brief, findings from this exploratory study offered a new insight on the roles of various bioactive lipid molecules in the development of coronary artery disease biomarkers.

  5. [Recent biochemical nutrition knowledge in relation to metabolism and the significance of essential fatty acids and n-3-fatty acids contained in fish]. (United States)

    Kolb, E


    A survey is given on some newer knowledge about metabolism and about the importance of the essential fatty acids and of the n-3 fatty acids (eicosapentaenic, docosapentaenic, docosahexaenic acids) which occur in fish oils. In the body the linoleic acid via intermediate steps can be transformed into the arachidonic acid, from which various prostaglandins and leucotriens as well as the thromboxane A2 can be formed. The transformation of the linolenic acid into the eicosapentaenic acid is slight in man. The docosahexaenic acid is necessary for the construction of phospholipids in the brain and in the retina. The uptake of fish fatty acids inhibits the formation of thromboxane A2 and of leukotriens from the arachidonic acid. The fish fatty acids further in the liver in the peroxisomas the activity of the enzymes for the beta-oxidation; the formation of lipoproteins of high density increases under their influence: the triacylglyceride content, the cholesterol as well as the lipoprotein content of very low and low density decreases, when there is an adequate part of fish fatty acids in the nutrition.

  6. Omega-3 fatty acids for breast cancer prevention and survivorship. (United States)

    Fabian, Carol J; Kimler, Bruce F; Hursting, Stephen D


    Women with evidence of high intake ratios of the marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) relative to the omega-6 arachidonic acid have been found to have a reduced risk of breast cancer compared with those with low ratios in some but not all case-control and cohort studies. If increasing EPA and DHA relative to arachidonic acid is effective in reducing breast cancer risk, likely mechanisms include reduction in proinflammatory lipid derivatives, inhibition of nuclear factor-κB-induced cytokine production, and decreased growth factor receptor signaling as a result of alteration in membrane lipid rafts. Primary prevention trials with either risk biomarkers or cancer incidence as endpoints are underway but final results of these trials are currently unavailable. EPA and DHA supplementation is also being explored in an effort to help prevent or alleviate common problems after a breast cancer diagnosis, including cardiac and cognitive dysfunction and chemotherapy-induced peripheral neuropathy. The insulin-sensitizing and anabolic properties of EPA and DHA also suggest supplementation studies to determine whether these omega-3 fatty acids might reduce chemotherapy-associated loss of muscle mass and weight gain. We will briefly review relevant omega-3 fatty acid metabolism, and early investigations in breast cancer prevention and survivorship.

  7. Changes in transepidermal water loss and the composition of epidermal lecithin after applications of pure fatty acid triglycerides to skin of essential fatty acid-deficient rats. (United States)

    Hartop, P J; Prottey, C


    The importance of various unsaturated fatty acid triglycerides to the repair of faulty skin barrier function was studied in essential fatty acid-deficient rats. Following cutaneous application of the pure triglycerides for up to 5 days, the hitherto high rate of transepidermal water loss, characteristic of essential fatty acid deficiency in rats, was reduced by the triglycerides of linoleic and gamma-linolenic acids. Incorporation of the applied fatty acids into the lecithin of the epidermis accompanied these changes in water loss, indicating that cutaneously applied triglycerides may be metabolized by the skin and incorporated into complex lipids. Other fatty acid triglycerides, including alpha-linolenic, dihomo-gamma-linolenic, arachidonic and omega-7-heneicosatrienoic acid, did not lower the rate of transepidermal water loss, although all were incorporated into epidermal structural lipids. The non-essential oleic acid also had no effect upon the rate of transepidermal water loss. These data suggest that of the two main essential fatty acids that occur in skin, linoleic acid and arachidonic acid, the former specifically plays an important role in regulating barrier function whereas the later may have a separate function, such as serving as a precursor of prostaglandins.

  8. Linoleic acid: between doubts and certainties. (United States)

    Choque, Benjamin; Catheline, Daniel; Rioux, Vincent; Legrand, Philippe


    Linoleic acid is the most abundant polyunsaturated fatty acid in human nutrition and represents about 14 g per day in the US diet. Following the discovery of its essential functions in animals and humans in the early 1920's, studies are currently questioning the real requirement of linoleic acid. It seems now overestimated and creates controversy: how much linoleic acid should be consumed in a healthy diet? Beyond the necessity to redefine the dietary requirement of linoleic acid, many questions concerning the consequences of its excessive consumption on human health arise. Linoleic acid is a direct precursor of the bioactive oxidized linoleic acid metabolites. It is also a precursor of arachidonic acid, which produces pro-inflammatory eicosanoids and endocannabinoids. A majority of the studies on linoleic acid and its derivatives show a direct/indirect link with inflammation and metabolic diseases. Many authors claim that a high linoleic acid intake may promote inflammation in humans. This review tries to (i) highlight the importance of reconsidering the actual requirement of linoleic acid (ii) point out the lack of knowledge between dietary levels of linoleic acid and the molecular mechanisms explaining its physiological roles (iii) demonstrate the relevance of carrying out further human studies on the single variable linoleic acid.

  9. Fatty acid-induced changes in vascular reactivity in healthy adult rats. (United States)

    Christon, Raymond; Marette, André; Badeau, Mylène; Bourgoin, Frédéric; Mélançon, Sébastien; Bachelard, Hélène


    Dietary fatty acids (FAs) are known to modulate endothelial dysfunction, which is the first stage of atherosclerosis. However, their exact role in this initial phase is still unclear. The effects of isolated or combined (by 2) purified FAs from the main FA families were studied on the vascular response of isolated thoracic aorta in healthy rats to get a better understanding of the mechanisms of action of dietary FAs in regulating vascular endothelial function. Cumulative contraction curves to phenylephrine and relaxation curves to carbachol and then to sodium nitroprusside were obtained in the absence or presence of the FAs studied allowing endothelium-dependent and endothelium-independent ability of the smooth muscle to relax to be assessed in each experimental group. The endothelium-dependent vasodilator response to carbachol was lowered by eicosapentaenoic acid, whereas it was not altered either by docosahexaenoic acid alone or by combined eicosapentaenoic acid-docosahexaenoic acid, oleic acid, or stearic acid, and it was increased by linoleic acid (LA). A decreased phenylephrine-induced contraction was observed after incubation with arachidonic acid and with stearic acid. On the other hand, the endothelium-dependent relaxation was reduced by the addition of combined LA-arachidonic acid and LA-oleic acid. In conclusion, these data point out the differential effects of different types of FAs and of FAs alone vs combined on vascular reactivity. The complex nature of these effects could be partially linked to metabolic specificities of endothelial cells and to interactions between some FAs.

  10. Bio conversion of ω-Fatty Acid from Giant Snake head (Channa micropeltes Fish Oil

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    Muhammad Nor Omar


    Full Text Available Study on bio conversion of ω-fatty acids extracted from giant snake head (Channa micropeltes fish oil was carried out using guinea pig lung homogenate. The fish oil, after hydrolysis to their fatty acids, was incubated aerobically at 37oC in phosphate buffer solution with the addition of guinea pig lung homogenate. After incubation and chemoreduction, it was found that ca. 76% arachidonic acid has been converted to the prostaglandin, PGE1. The fatty acid constituents in fish oil were analysed by GC-MS after methylation.

  11. Erythrocyte levels compared with reported dietary intake of marine n-3 fatty acids in pregnant women

    DEFF Research Database (Denmark)

    Olsen, S.F.; Hansen, H.S.; Sandstrom, B.;


    dietary self- administered questionnaire and interview, with fatty acids measured in erythrocyte phospholipids. Daily intake (g/d) and nutrient density of marine n-3 fatty acids (mg/MJ) correlated with the n-3 fatty acid: arachidonic acid ratio (FA-ratio) with correlation coefficients of 0.48 and 0.......54 respectively. In a linear regression model with three frequency questions about marine sandwiches, marine cooked meals and fish oil as explanatory variables, and the FA-ratio as dependent variable, the multiple correlation coefficient was 0.46. Conclusions from the study were (1) levels of erythrocyte fatty...

  12. Erythrocyte levels compared with reported dietary intake of marine n-3 fatty acids in pregnant women

    DEFF Research Database (Denmark)

    Olsen, S.F.; Hansen, Harald S.; Sandstrom, B.;


    dietary self-administered questionnaire and interview, with fatty acids measured in erythrocyte phospholipids. Daily intake (g/d) and nutrient density of marine n-3 fatty acids (mg/MJ) correlated with the n-3 fatty acid: arachidonic acid ratio (FA-ratio) with correlation coefficients of 0.48 and 0.......54 respectively. In a linear regression model with three frequency questions about marine sandwiches, marine cooked meals and fish oil as explanatory variables, and the FA-ratio as dependent variable, the multiple correlation coefficient was 0.46. Conclusions from the study were (1) levels of erythrocyte fatty...

  13. Reversible phenotypic modulation induced by deprivation of exogenous essential fatty acids. (United States)

    Laposata, M; Minda, M; Capriotti, A M; Hartman, E J; Furth, E E; Iozzo, R V


    Essential fatty acid deficiency, produced by deprivation of omega-6 and omega-3 fatty acids, is a condition characterized by renal disease, dermatitis, and infertility. Although many of the biochemical aspects of this disorder have been investigated, little is known about the ultrastructural changes induced by essential fatty acid deficiency. Using a unique fatty acid-deficient cell line (EFD-1), which demonstrates the in vivo fatty acid changes of essential fatty acid deficiency, and the prostaglandin E2-producing mouse fibrosarcoma line from which it was derived (HSDM1C1), we correlated ultrastructural and biochemical changes induced by prolonged deprivation of all exogenous lipids and subsequent repletion of selected essential fatty acids. We found that in cells deprived of all exogenous lipids, there was dilation of rough endoplasmic reticulum and an associated defect in protein secretion; these changes were specifically reversed by arachidonate. There was also an accumulation of secondary lysosomes containing degraded membranes in these cells with an associated increase in phospholipids relative to parent HSDM1C1 cells. Cytoplasmic lipid bodies present in parent cells disappeared, with an associated decrease in triacylglycerol. After just 2 days in lipid-free medium, all these changes were apparent, and prostaglandin E2 production was markedly impaired despite normal amounts of cellular arachidonate. Incubation of EFD-1 cells with arachidonate, the major prostaglandin precursor fatty acid, induced a reversion to the HSDM1C1 phenotype, whereas other fatty acids were totally ineffective. These results indicate changes in fatty acid metabolism in essential fatty acid deficiency are associated with marked alterations in ultrastructure and secretion of protein from cells.

  14. Erythrocyte phospholipid and polyunsaturated fatty acid composition in diabetic retinopathy.

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    Philippe Koehrer

    Full Text Available Long chain polyunsaturated fatty acids (LCPUFAs including docosahexaenoic acid and arachidonic acid are suspected to play a key role in the pathogenesis of diabetes. LCPUFAs are known to be preferentially concentrated in specific phospholipids termed as plasmalogens. This study was aimed to highlight potential changes in the metabolism of phospholipids, and particularly plasmalogens, and LCPUFAs at various stages of diabetic retinopathy in humans.We performed lipidomic analyses on red blood cell membranes from controls and mainly type 2 diabetes mellitus patients with or without retinopathy. The fatty acid composition of erythrocytes was determined by gas chromatography and the phospholipid structure was determined by liquid chromatography equipped with an electrospray ionisation source and coupled with a tandem mass spectrometer (LC-ESI-MS/MS. A significant decrease in levels of docosahexaenoic acid and arachidonic acid in erythrocytes of diabetic patients with or without retinopathy was observed. The origin of this decrease was a loss of phosphatidyl-ethanolamine phospholipids esterified with these LCPUFAs. In diabetic patients without retinopathy, this change was balanced by an increase in the levels of several phosphatidyl-choline species. No influence of diabetes nor of diabetic retinopathy was observed on the concentrations of plasmalogen-type phospholipids.Diabetes and diabetic retinopathy were associated with a reduction of erythrocyte LCPUFAs in phosphatidyl-ethanolamines. The increase of the amounts of phosphatidyl-choline species in erythrocytes of diabetic patients without diabetic retinopathy might be a compensatory mechanism for the loss of LC-PUFA-rich phosphatidyl-ethanolamines.

  15. Specific markers of lipid peroxidation issued from n-3 and n-6 fatty acids. (United States)

    Guichardant, M; Chantegrel, B; Deshayes, C; Doutheau, A; Moliere, P; Lagarde, M


    Several markers of lipid peroxidation are available with different degrees of specificity, from malondialdehyde as a global marker, to F(2)-isoprostane, which is specifically produced from arachidonic acid. Among these, 4-hydroxynonenal is recognized as a breakdown product of fatty acid hydroperoxides, such as 15-hydroperoxy-eicosatetraenoic acid and 13-hydroperoxy-octade cadienoic acid from the n -6 fatty acids. Furthermore, 4-hydroxyhexenal (4-HHE) derives from n -3 fatty acid hydroperoxides. We have recently described the occurrence of 4-hydroxydodecadienal (4-HDDE) from the 12-lipoxygenase product of arachidonic acid 12-hydroperoxy-eicosatetraenoic acid. These three hydroxy-alkenals may be measured in human plasma by GC-MS, but they may partly be generated in the course of sampling, and the relative volatility of 4-HHE makes its measurement quite unreliable. We have successfully characterized and measured the stable oxidized carboxylic acid products from the hydroxy-alkenals 4-HNA, 4-HHA and 4-HDDA in urine. The ratio between 4-HHA and 4-HNA found in the same urinary sample might provide useful information on the location of lipid peroxidation, accounting for the high enrichment of the cerebrovascular system with docosahexaenoic acid, the main n -3 fatty acid in humans.

  16. Polyunsaturated fatty acid metabolites as novel lipidomic biomarkers for noninvasive diagnosis of nonalcoholic steatohepatitis1


    Loomba, Rohit; Quehenberger, Oswald; Armando, Aaron; Dennis, Edward A.


    Lipotoxicity is a key mechanism thought to be responsible for the progression of nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). Noninvasive diagnosis of NASH is a major unmet clinical need, and we hypothesized that PUFA metabolites, in particular arachidonic acid (AA)-derived eicosanoids, in plasma would differentiate patients with NAFL from those with NASH. Therefore, we aimed to assess the differences in the plasma eicosanoid lipidomic profile between patients with ...

  17. 5-Lipoxygenase inhibition by acetyl-11-keto-β-boswellic acid (AKBA) by a novel mechanism. (United States)

    Safayhi, H; Sailer, E R; Ammon, H P


    Acetyl-11-keto-β-boswellic acid (AKAB) from Boswellia serrata and B. carterii acts directly on purified 5-lipoxygenase of human blood leukocytes at a selective site for pentacyclic triterpenes that is different from the arachidonate substrate binding site. The pentacyclic triterpene ring is crucial for binding to the enzyme, whereas functional groups (11-keto function in addition to a hydrophilic group on C 4 of ring A) are essential for the 5-lipoxygenase activity.

  18. Epoxyeicosatrienoic acids and glucose homeostasis in mice and men. (United States)

    Luther, James M; Brown, Nancy J


    Epoxyeicosatrienoic acids (EETs) are formed from arachidonic acid by the action of P450 epoxygenases (CYP2C and CYP2J). Effects of EETs are limited by hydrolysis by soluble epoxide hydrolase to less active dihydroxyeicosatrienoic acids. Studies in rodent models provide compelling evidence that epoxyeicosatrienoic acids exert favorable effects on glucose homeostasis, either by enhancing pancreatic islet cell function or by increasing insulin sensitivity in peripheral tissues. Specifically, the tissue expression of soluble epoxide hydrolase appears to be increased in rodent models of obesity and diabetes. Pharmacological inhibition of epoxide hydrolase or deletion of the gene encoding soluble epoxide hydrolase (Ephx2) preserves islet cells in rodent models of type 1 diabetes and enhances insulin sensitivity in models of type 2 diabetes, as does administration of epoxyeicosatrienoic acids or their stable analogues. In humans, circulating concentrations of epoxyeicosatrienoic acids correlate with insulin sensitivity, and a loss-of-function genetic polymorphism in EPHX2 is associated with insulin sensitivity.

  19. Feedlot lamb meat fatty acids profile characterization employing gas chromatography

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    M.I. Cruz-Gonzalez


    Full Text Available Fat is an important constituent in diet, not only as an energy source, but for its essential fatty acids associated to fats in foods, considering that some polyunsaturated fatty acids like linoleic, linolenic and arachidonic cannot be synthesized by superior animals like humans. Scientific evidence show that the fatty acids ingest can affect the thrombotic tendency, cardiac rhythm, endothelial function systematic inflammation, insulin sensibility and oxidative stress. Samples from 21 ovine crossbreds from Pelibuey, Blackbelly, Dorper and Katahadin (40 kg average weight feed with corn based balanced diets were taken from loin area 18 h after refrigeration. Saturated and polyunsaturated fatty acids levels were analyzed by gas chromatography. Results in this work showed that the healthy fatty acids levels are higher as compared to saturated fatty acids levels, indicating that this meat can influence consumer’s buying choice decision regarded to their health.

  20. [Effect of the B-group vitamin complex on the blood content of saturated and unsaturated fatty acids in patients with ischemic heart disease and hypertension]. (United States)

    Vodoevich, V P; Buko, V U


    Gas-liquid chromatography was used to study the blood content of saturated and unsaturated fatty acids, under the influence of the functionally-associated vitamin-B complex, in 45 patients with coronary heart disease and essential hypertension. The vitamins were given daily in the following doses: thiamine diphosphate 50 mg, riboflavine 40 mg, calcium pantothenate 200 mg, nicotinic acid 200 mg and lipoic acid 50 mg. Favourable shifts leading to positive clinical effects were recorded in the fatty acid metabolism after 10-day taking the vitamin-B complex: the content of unsaturated (linoleic and arachidonic) fatty acids increased while that of saturated (stearic and palmitic) fatty acids decreased.

  1. Identification of saturated and unsaturated fatty acids released during microsomal incubations. (United States)

    Bushee, Jennifer L; Liang, Guiqing; Dunne, Christine E; Harriman, Shawn P; Argikar, Upendra A


    1. In vitro clearance in liver microsomes is routinely measured in drug discovery and development for new chemical entities. Literature reports indicate that long chain fatty acids such as arachidonic, linoleic and oleic acids may be released over a period of time during microsomal incubations. Some fatty acids have been shown to interfere with oxidative and conjugative reactions in microsomes, thus potentially inhibiting microsomal clearance of compounds. 2. The present study was aimed at deciphering the fatty acids present or released from microsomes. Analytical methods were developed to characterize and quantitatively assess the fatty acids without chemical derivatization in rat, monkey and human liver microsomes. Additionally, incubations with uridine-5'-diphosphoglucuronic acid (UDPGA) were utilized to trap the released fatty acids as their glucuronate esters, which were characterized and confirmed by high-resolution LC-MS/MS. 3. Our results indicate for the first time that timnodonic, trans-eicosenoic, gondoic, behenic, and nervonic acid were released during microsomal incubations. Additionally, α- and γ-linolenic, timnodonic, palmitoleic, linoleic, arachidonic, palmitic, oleic, and stearic acid were identified as their corresponding acyl-glucuronides in rat, monkey and human liver microsomes, providing the first direct evidence that the released fatty acids are capable of forming glucuronides under incubation conditions.

  2. Structural Insight into the Differential Effects of Omega-3 and Omega-6 Fatty Acids on the Production of Aβ Peptides and Amyloid Plaques*


    Amtul, Zareen; Uhrig, Markus; Rozmahel, Richard F.; Beyreuther, Konrad


    Several studies have shown the protective effects of dietary enrichment of various lipids in several late-onset animal models of Alzheimer Disease (AD); however, none of the studies has determined which structure within a lipid determines its detrimental or beneficial effects on AD. High-sensitivity enzyme-linked immunosorbent assay (ELISA) shows that saturated fatty acids (SFAs), upstream omega-3 FAs, and arachidonic acid (AA) resulted in significantly higher secretion of both Aβ 40 and 42 p...

  3. Immunoregulatory and anti-inflammatory effects of n-3 polyunsaturated fatty acids

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    P.C. Calder


    Full Text Available 1. Fish oils are rich in the long-chain n-3 polyunsaturated fatty acids (PUFAs, eicosapentaenoic (20:5n-3 and docosahexaenoic (22:6n-3 acids. Linseed oil and green plant tissues are rich in the precursor fatty acid, a-linolenic acid (18:3n-3. Most vegetable oils are rich in the n-6 PUFA linoleic acid (18:2n-6, the precursor of arachidonic acid (20:4n-6. 2. Arachidonic acid-derived eicosanoids such as prostaglandin E2 are pro-inflammatory and regulate the functions of cells of the immune system. Consumption of fish oils leads to replacement of arachidonic acid in cell membranes by eicosapentaenoic acid. This changes the amount and alters the balance of eicosanoids produced. 3. Consumption of fish oils diminishes lymphocyte proliferation, T-cell-mediated cytotoxicity, natural killer cell activity, macrophage-mediated cytotoxicity, monocyte and neutrophil chemotaxis, major histocompatibility class II expression and antigen presentation, production of pro-inflammatory cytokines (interleukins 1 and 6, tumour necrosis factor and adhesion molecule expression. 4. Feeding laboratory animals fish oil reduces acute and chronic inflammatory responses, improves survival to endotoxin and in models of autoimmunity and prolongs the survival of grafted organs. 5. Feeding fish oil reduces cell-mediated immune responses. 6. Fish oil supplementation may be clinically useful in acute and chronic inflammatory conditions and following transplantation. 7. n-3 PUFAs may exert their effects by modulating signal transduction and/or gene expression within inflammatory and immune cells.

  4. Whole Blood Levels of the n-6 Essential Fatty Acid Linoleic Acid Are Inversely Associated with Stunting in 2-to-6 Year Old Tanzanian Children: A Cross-Sectional Study.

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    Theresia Jumbe

    Full Text Available In Tanzania, 35% of all children below five years of age are stunted. Dietary fatty acids (FA are critical for growth and development. However, whole blood FA levels in Tanzanian children are poorly described.The objectives of this cross-sectional study were to assess 1 whole blood levels of essential fatty acids and 2 the association between whole blood FA levels and growth parameters in Tanzanian children 2-6 years of age.A drop of blood was collected on an antioxidant treated card and analyzed for FA composition. Weight and height were measured and z-scores calculated. Relationships between FAs and growth parameters were analyzed by linear regression.Of the 334 children that participated, 30.3% were stunted. The average whole blood level of Mead acid was 0.15%. The anthropometric z-score height-for-age (HAZ was inversely associated with Mead acid, the Mead acid to arachidonic acid (T/T ratio, and total n-9 FA. Additionally, HAZ was positively associated with linoleic acid and total n-6 FA. BMI-for-age was positively associated with oleic acid, total n-9 FA and T/T ratio but inversely associated with arachidonic acid and total n-6 FA. Weight-for-height was inversely associated with arachidonic acid and total n-6 FAs and positively associated with oleic acid and total n-9 FA. Weight-for-age was not associated with any FA tested. Total n-3 FAs were not associated with any growth parameters measured.The EFA linoleic acid and the markers of FA deficiency were associated with HAZ, an indicator for stunting in 2-6 year old Tanzanian children. Total n-6, total n-9, and a number of individual FAs were associated with growth. Increasing dietary intake of EFA and n-6 FAs may be a strategy to combat stunting in this population.

  5. Fatty acid composition of brown adipose tissue in genetically heat-tolerant FOK rats (United States)

    Ohno, T.; Furuyama, F.; Kuroshima, A.

    The phospholipid fatty acid composition of brown adipose tissue (BAT) was examined in inbred heat-tolerant FOK rats and compared with that in conventional Wistar rats not previously exposed to heat. The FOK rats showed higher unsaturation states, as indicated by higher levels of polyunsaturated fatty acids and a higher unsaturation index and polyunsaturated fatty acids/saturated fatty acids ratio. This higher level of unsaturation was characterized by the higher amount of polyunsaturated fatty acids such as linoleic acid, arachidonic acid and docosahexaenoic acid. It may be concluded that the increased docosahexaenoic acid level in BAT phospholipids brings about the hyperplasia of BAT, causing an enhancement of its in vivo thermogernic activity as well as the systemic non-shivering thermogenesis observed in heat-tolerant FOK rats.

  6. [Value of Fatty acids in formation of thrombotic status in patients with ischemic heart disease]. (United States)

    Sokolov, E I; Zykova, A A; Sushchik, V V; Goncharov, I N


    Interrelation between fatty acids and platelet aggregation has been a subject of interest for cardiologists in the terms of thrombogenic status. In order to study this problem we observed 42 patients with ischemic heart disease and 30 healthy persons. In patients we found elevation of arachidonic acid and lowering of docosahexaenic acid levels. Hypoxemic assay revealed in these patients lowering of prostacyclin and antithrombin III levels. In the pathogenesis of disturbances of platelet aggregation in patients with ischemic heart disease alteration of structure of platelets with increased quantity of phosphatidyl ethanolamine and corresponding change of thrombocyte asymmetry resulted in conformational reorganization of proteins and lipids.

  7. Effect of fatty acids on leukocyte function

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    Pompéia C.


    Full Text Available Fatty acids have various effects on immune and inflammatory responses, acting as intracellular and intercellular mediators. Polyunsaturated fatty acids (PUFAs of the omega-3 family have overall suppressive effects, inhibiting lymphocyte proliferation, antibody and cytokine production, adhesion molecule expression, natural killer cell activity and triggering cell death. The omega-6 PUFAs have both inhibitory and stimulatory effects. The most studied of these is arachidonic acid that can be oxidized to eicosanoids, such as prostaglandins, leukotrienes and thromboxanes, all of which are potent mediators of inflammation. Nevertheless, it has been found that many of the effects of PUFA on immune and inflammatory responses are not dependent on eicosanoid generation. Fatty acids have also been found to modulate phagocytosis, reactive oxygen species production, cytokine production and leukocyte migration, also interfering with antigen presentation by macrophages. The importance of fatty acids in immune function has been corroborated by many clinical trials in which patients show improvement when submitted to fatty acid supplementation. Several mechanisms have been proposed to explain fatty acid modulation of immune response, such as changes in membrane fluidity and signal transduction pathways, regulation of gene transcription, protein acylation, and calcium release. In this review, evidence is presented to support the proposition that changes in cell metabolism also play an important role in the effect of fatty acids on leukocyte functioning, as fatty acids regulate glucose and glutamine metabolism and mitochondrial depolarization.

  8. Essential fatty acids and lipid mediators. Endocannabinoids

    Directory of Open Access Journals (Sweden)

    G. Caramia


    Full Text Available In 1929 Burr and Burr discovered the essential fatty acids omega-6 and omega-3. Since then, researchers have shown a growing interest in polyunsaturated fatty acids (PUFA as precursors of “lipid mediator” molecules, often with opposing effects, prostaglandins, prostacyclins, thromboxanes, leukotrienes, lipossines, resolvines, protectines, maresins that regulate immunity, platelet aggregation, inflammation, etc. They showed that the balance between omega-3 and omega-6 acids has a profound influence on all the body’s inflammatory responses and a raised level of PUFA omega-3 in tissue correlate with a reduced incidence of degenerative cardiovascular disease, some mental illnesses such as depression, and neuro-degenerative diseases such as Alzheimer’s. The CYP-catalyzed epoxidation and hydroxylation of arachidonic acid (AA were established recently as the so-called third branch of AGE cascade. Cytochrome P450 (CYP epoxygenases convert AA to four epoxyeicosatrienoic acid (EET regioisomers, that produce vascular relaxation anti-inflammatory effects on blood vessels and in the kidney, promote angiogenesis, and protect ischemic myocardium and brain. Eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA are accessible to CYP enzymes in the same way as AA. Metabolites derived from EPA include epoxyeicosatetraenoic acids (EETR and hydroxyeicosapentaenoic acids (19- and 20-HEPE, whereas DHA include epoxydocosapentaenoic acids (EDPs hydroxydocosahexaenoic acids (21- and 22-HDoHE. For many of the CYP isoforms, the n-3 PUFAs are the preferred substrates and the available data suggest that some of the vasculo- and cardioprotective effects attributed to dietary n-3 PUFAs may be mediated by CYP-dependent metabolites of EPA and DHA. From AA derives also endocannabinoids like anandamide (N-arachidonoylethanolamine and 2-arachidonoylglycerol, capable of mimicking the pharmacological actions of the active principle of Cannabis sativa preparations such as

  9. The effects of season on fatty acid composition and ω3/ω6 ratios of northern pike ( Esox lucius L., 1758) muscle lipids (United States)

    Mert, Ramazan; Bulut, Sait; Konuk, Muhsin


    In the present study, the effects of season on fatty acid composition, total lipids, and ω3/ω6 ratios of northern pike muscle lipids in Kizilirmak River (Kirikkale, Turkey) were investigated. A total of 35 different fatty acids were determined in gas chromatography. Among these, palmitic, oleic, and palmitoleic acids had the highest proportion. The main polyunsaturated fatty acids (PUFAs) were found to be docosahexaenoic acid, eicosapentaenoic acid, and arachidonic acid. There were more PUFAs than monounsaturated fatty acids (MUFA) in all seasons. Similarly, the percentages of ω3 fatty acids were higher than those of total ω6 fatty acids in the fatty acid composition. ω3/ω6 ratios were calculated as 1.53, 1.32, 1.97, and 1.71 in spring, summer, autumn and winter, respectively. Overall, we found that the fatty acid composition and ω3/ω6 fatty acid ratio in the muscle of northern pike were significantly influenced by season.

  10. Selective remodeling of cardiolipin fatty acids in the aged rat heart

    Directory of Open Access Journals (Sweden)

    Rapoport Stanley I


    Full Text Available Abstract Background The heart is rich in cardiolipin, a phospholipid acylated in four sites, predominately with linoleic acid. Whether or not aging alters the composition of cardiolipin acyl chains is controversial. We therefore measured the fatty acid concentration of cardiolipin in hearts of 4, 12 and 24 month old rats that consumed one diet, adequate in fatty acids for the duration of their life. Results The concentration (nmol/g of linoleic acid was decreased in 24 month old rats (3965 ± 617, mean ± SD vs 4 month old rats (5525 ± 656, while the concentrations of arachidonic and docosahexaenoic acid were increased in 24 month old rats (79 ± 9 vs 178 ± 27 and 104 ± 16 vs 307 ± 68 for arachidonic and docosahexaenoic acids, 4 months vs 24 months, respectively. Similar changes were not observed in ethanolamine glycerophospholipids or plasma unesterified fatty acids, suggesting specificity of these effects to cardiolipin. Conclusion These results demonstrate that cardiolipin remodeling occurs with aging, specifically an increase in highly unsaturated fatty acids.

  11. Effect of Growth on Fatty Acid Composition of Total Intramuscular Lipid and Phospholipids in Ira Rabbits. (United States)

    Xue, Shan; He, Zhifei; Lu, Jingzhi; Tao, Xiaoqi; Zheng, Li; Xie, Yuejie; Xiao, Xia; Peng, Rong; Li, Hongjun


    The changes in fatty acid composition of total intramuscular lipid and phospholipids were investigated in the longissimus dorsi, left-hind leg muscle, and abdominal muscle of male Ira rabbits. Changes were monitored at 35, 45, 60, 75, and 90 d. Analysis using gas chromatography identified 21 types of fatty acids. Results showed that the intramuscular lipid increased and the intramuscular phospholipids (total intramuscular lipid %) decreased in all muscles with increasing age (pIra rabbits at different ages and muscles. Palmitic acid (C16:0), stearic acid (C18:0), oleic acid (C18:1), linoleic acid (C18:2), and arachidonic acid (C20:4) were the major fatty acids, which account to the dynamic changes of the n-6/n-3 value in Ira rabbit meat.

  12. Accumulation of eicosapolyenoic acids enhances sensitivity to abscisic acid and mitigates the effects of drought in transgenic Arabidopsis thaliana. (United States)

    Yuan, Xiaowei; Li, Yaxiao; Liu, Shiyang; Xia, Fei; Li, Xinzheng; Qi, Baoxiu


    IgASE1, a C₁₈ Δ(9)-specific polyunsaturated fatty acid elongase from the marine microalga Isochrysis galbana, is able to convert linoleic acid and α-linolenic acid to eicosadienoic acid and eicosatrienoic acid in Arabidopsis. Eicosadienoic acid and eicosatrienoic acid are precursors of arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid, which are synthesized via the Δ(8) desaturation biosynthetic pathways. This study shows that the IgASE1-expressing transgenic Arabidopsis exhibited altered morphology (decreased leaf area and biomass) and enhanced drought resistance compared to wild-type plants. The transgenic Arabidopsis were hypersensitive to abscisic acid (ABA) during seed germination, post-germination growth, and seedling development. They had elevated leaf ABA levels under well-watered and dehydrated conditions and their stomata were more sensitive to ABA. Exogenous application of eicosadienoic acid and eicosatrienoic acid can mimic ABA and drought responses in the wild type plants, similar to that found in the transgenic ones. The transcript levels of genes involved in the biosynthesis of ABA (NCED3, ABA1, AAO3) as well as other stress-related genes were upregulated in this transgenic line upon osmotic stress (300 mM mannitol). Taken together, these results indicate that these two eicosapolyenoic acids or their derived metabolites can mitigate the effects of drought in transgenic Arabidopsis, at least in part, through the action of ABA.

  13. Glucagon-like peptide 1 receptor activation regulates cocaine actions and dopamine homeostasis in the lateral septum by decreasing arachidonic acid levels

    DEFF Research Database (Denmark)

    Reddy, I A; Pino, J A; Weikop, P


    Agonism of the glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) has been effective at treating aspects of addictive behavior for a number of abused substances, including cocaine. However, the molecular mechanisms and brain circuits underlying the therapeutic effects of GLP-1R signaling on cocaine...... plasma membrane expression and function. These results support a mechanism in which postsynaptic septal GLP-1R activation regulates 2-AG levels to alter presynaptic DA homeostasis and cocaine actions through AA....... actions remain elusive. Recent evidence has revealed that endogenous signaling at the GLP-1R within the forebrain lateral septum (LS) acts to reduce cocaine-induced locomotion and cocaine conditioned place preference, both considered dopamine (DA)-associated behaviors. DA terminals project from...

  14. Arachidonic acid mediates non-capacitative calcium entry evoked by CB1-cannabinoid receptor activation in DDT1 MF-2 smooth muscle cells

    NARCIS (Netherlands)

    Demuth, D.G.; Gkoumassi, Effimia; Droge, M.J.; Dekkers, B.G.J.; Esselink, H.J.; van Ree, Rutger; Parsons, M.E.; Zaagsma, Hans; Molleman, A; Nelemans, Herman


    Cannabinoid CB1-receptor stimulation in DDT1 MF-2 smooth muscle cells induces a rise in [Ca2+](i), which is dependent on extracellular Ca2+ and modulated by thapsigargin-sensitive stores, suggesting capacitative Ca2+ entry (CCE), and by MAP kinase. Non-capacitative Ca2+ entry (NCCE) stimulated by ar

  15. Effect of various eicosanoid products of arachidonic acid on the acyl CoA: Cholesterol acyl transferase activity in three different mammalian cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Malo, P.El.


    Acylcoenzyme A:cholesterol acyltransferase (ACAT) catalyzes cholesterol ester synthesis intracellularly and has been implicated in the development of atherosclerosis. An in vitro assay has been adapted for determining ACAT activity from rat FU5AH hepatoma, Chinese hamster ovary (CHO) and rat thoracic aortic smooth muscle (RSM) cells. Formation of {sup 14}C-labelled cholesteryl oleate at 0 to 60 min {plus minus} cholesterol was determined; in the presence of exogenous cholesterol, ACAT activity was approximately linear and surpassed the plateau observed in ACAT activity without cholesterol. Increasing exogenous cholesterol concentration, the amount of oleoyl CoA or the amount of microsomal protein produced a corresponding increase in ACAT activity, while ester formation was slightly increased by decreasing the ratio of Triton WR-1339 to cholesterol. Both the thromboxane A{sub 2} (TxA{sub 2}) mimic, U-44069, and the inflammatory lipoxygenase product, LTB{sub 4}, decreased optimal in vitro microsomal ACAT activity from RSM, but not form FU5AH, while CHO ACAT activity was suppressed by LTB{sub r} only. PGI{sub 2}, PGE{sub 2} and PGF{sub 2{alpha}} had minimal effects for each cell type.

  16. Arachidonic Acid Metabolism in the Nervous System; Physiological and Pathological Significance. Annals of the New York Academy of Science. Volume 5 (United States)


    effects of vasopressin and synthetic ovine CRF 7 and GRF2" on PGE2 synthesis by the rat adenohypophysis . The other prostanoids were not formed under...latter exerts a tonic inhibitory influence on the release of growth hormone from the adenohypophysis and modulates CNS synaptic transmission

  17. Attenuation of Thrombosis by Crude Rice (Oryza sativa) Bran Policosanol Extract: Ex Vivo Platelet Aggregation and Serum Levels of Arachidonic Acid Metabolites (United States)

    Ismail, Maznah; Tohit, Eusni Rahayu Mohd; Abdullah, Rasedee; Zhang, Yi-Da


    Background. Vascular occlusion or thrombosis was often attributed to uncontrolled platelet activation. Influence of sugarcane policosanol extract on platelet was reported but little was known of rice bran policosanol, particularly its mechanisms of actions on platelet activities. Objective. Antiplatelet mechanisms of rice bran policosanol extract (RBE) were studied using hyperlipidemic Sprague Dawley rats. Ex vivo platelet aggregation, platelet count (PC), bleeding time (BT), and coagulation time were assayed. Serum eicosanoids and other aggregation-related metabolites levels were quantified. Design. Rats were divided into 6 groups for comparisons (vehicle control Tween 20/H2O, high dose policosanol 500 mg/kg, middle dose policosanol 250 mg/kg, low dose policosanol 100 mg/kg, and positive control aspirin 30 mg/kg). Results. Low dose 100 mg/kg of RBE inhibited aggregation by 42.32 ± 4.31% and this was comparable with the effect of 30 mg/kg aspirin, 43.91 ± 5.27%. Results showed that there were no significant differences in PC, BT, and coagulation time among various groups after RBE treatment. Serum thromboxane A2 was attenuated while prostacyclin level increased upon RBE treatment. Conclusions. RBE reduced ex vivo ADP-induced platelet aggregation without giving adverse effects. No changes in full blood count suggested that rice bran policosanol did not disturb biological blood cell production and destruction yet it reduced aggregation through different mechanisms. PMID:27800004

  18. Abnormal essential fatty acid composition of tissue lipids in genetically diabetic mice is partially corrected by dietary linoleic and gamma-linolenic acids. (United States)

    Cunnane, S C; Manku, M S; Horrobin, D F


    Genetically diabetic mice (db/db) and their non-diabetic litter-mates were maintained for 15 weeks on diets supplemented with safflower oil or evening primrose (Oenothera bienis) oil, both essential fatty acid (EFA)-rich sources, or hydrogenated coconut oil (devoid of EFA). Plasma glucose was higher in the diabetic mice supplemented with the oils than in the unsupplemented diabetic mice. In the oil-supplemented non-diabetic mice, plasma glucose did not differ compared with the unsupplemented non-diabetic mice. The proportional content of arachidonic acid in the phospholipids of the pancreas was significantly decreased in diabetic mice, an effect which was completely prevented by supplementation with safflower or evening primrose oil but not hydrogenated coconut oil. In the liver phospholipids of the diabetic mice, dihomo-gamma-linolenic acid was proportionally increased, an effect reduced by supplementation with safflower oil but not evening primrose or hydrogenated coconut oils. In the liver triglycerides of the diabetic mice, gamma-linolenic acid, dihomo-gamma-linolenic acid and arachidonic acid were all proportionally decreased, effects which were also prevented by safflower or evening primrose oil but not hydrogenated coconut oil. Alopecia and dry scaly skin were prominent in the diabetic mice but less extensive in the diabetic mice supplemented with EFA.

  19. Fatty Acid Modulation of the Endocannabinoid System and the Effect on Food Intake and Metabolism

    Directory of Open Access Journals (Sweden)

    Shaan S. Naughton


    Full Text Available Endocannabinoids and their G-protein coupled receptors (GPCR are a current research focus in the area of obesity due to the system’s role in food intake and glucose and lipid metabolism. Importantly, overweight and obese individuals often have higher circulating levels of the arachidonic acid-derived endocannabinoids anandamide (AEA and 2-arachidonoyl glycerol (2-AG and an altered pattern of receptor expression. Consequently, this leads to an increase in orexigenic stimuli, changes in fatty acid synthesis, insulin sensitivity, and glucose utilisation, with preferential energy storage in adipose tissue. As endocannabinoids are products of dietary fats, modification of dietary intake may modulate their levels, with eicosapentaenoic and docosahexaenoic acid based endocannabinoids being able to displace arachidonic acid from cell membranes, reducing AEA and 2-AG production. Similarly, oleoyl ethanolamide, a product of oleic acid, induces satiety, decreases circulating fatty acid concentrations, increases the capacity for β-oxidation, and is capable of inhibiting the action of AEA and 2-AG in adipose tissue. Thus, understanding how dietary fats alter endocannabinoid system activity is a pertinent area of research due to public health messages promoting a shift towards plant-derived fats, which are rich sources of AEA and 2-AG precursor fatty acids, possibly encouraging excessive energy intake and weight gain.


    Directory of Open Access Journals (Sweden)

    Muhammad Ikbal Illijas


    Full Text Available High content of polyunsaturated fatty acids (PUFAs such as arachidonic and eicosapentaenoic acids are typical for the red alga. Analysis of fatty acid composition and prostaglandin content was conducted in the red alga Gracilaria sp. from Indonesia. Total lipid of the alga was extracted with CHCl3-MeOH (2:1, v/v. Analysis of the fatty acids composition was performed on gas chromatography (GC equipped with omega wax column (30 m x 0,32 mm i.d., Supelco, PA, USA and analysis of prostaglandins were carried out by HPLC on ODS column (Mightysil RP-18 GP, 250 mm x 4.6 mm, 5 μm. The content of fatty acids high for were palmitic acid (50% and arachidonic acid (26.9%, whereas prostaglandin E2 was identified and found lower concentration (44.2 μg/gram total lipid.

  1. Measurement of 12(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid and its metabolite 12-oxo-5Z,8E,10E-heptadecatrienoic acid in human plasma by gas chromatography/negative ion chemical ionization mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Hofmann, U.; Seefried, S.; Meese, C.O.; Mettang, T.; Huebel, E.K.; Kuhlmann, U. (Dr. Margarete Fischer-Bosch-Institut fuer Klinische Pharmakologie, Stuttgart (Germany, F.R.))


    Thromboxane A2, the predominant product of arachidonic acid metabolism in the blood platelet, is a potent vasoconstrictor and platelet agonist. During its biosynthesis from cyclic endoperoxide, 12(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid (HHT) is formed in equal amounts. The further metabolism of HHT, catalyzed by 15-hydroxyprostaglandin dehydrogenase, leads to 12-oxo-5Z,8E,10E-heptadecatrienoic acid (Oxo-HT). Sample workup procedures are described which allow for the sensitive and reproducible determination of these two arachidonic acid metabolites in human plasma by gas chromatography-mass spectrometry in the presence of deuterated analogues as internal standards. HHT is derivatized to the pentafluorobenzyl ester tert-butyldimethylsilyl ether. In order to enable quantification of low concentrations of about 10 pg/ml in nonstimulated human plasma, the samples have to be purified by HPLC. Oxo-HT is derivatized to the pentafluorobenzyl ester, which is purified by HPLC, and then derivatized to the trimethylsilyloxime. The method allows quantification of Oxo-HT in concentrations down to 10 pg/ml plasma. The reported methods have been used to measure HHT and Oxo-HT in stimulated platelet rich plasma and to quantify HHT in nonstimulated plasma. Determination of endogenous levels of these two arachidonic acid metabolites may give new insights into the overall biosynthesis of thromboxane A2 in man.

  2. In vivo incorporation of labeled fatty acids in rat liver lipids after oral administration

    Energy Technology Data Exchange (ETDEWEB)

    Leyton, J.; Drury, P.J.; Crawford, M.A.


    Striking differences were found in the compartmentalization of fatty acids into liver lipid fractions. The saturated fatty acids--lauric, myristic, palmitic and stearic--were incorporated into phosphoglycerides at faster rates with increasing chain lengths, while triglyceride incorporation was almost uniform. The degree of incorporation of the unsaturated fatty acids into phosphoglycerides (structural) compared to triglyceride (storage and energy) was the converse of their oxidation rates. The incorporation of oleic, linoleic and alpha-linolenic acids was mainly into triglyceride, whereas dihomo-gamma-linolenic acid and arachidonic acid were preferentially incorporated into phosphoglycerides. The data suggest that distribution of each fatty acid is different depending on its destination for structural or energy function.

  3. Impact of dietary fatty acids on muscle composition, liver lipids, milt composition and sperm performance in European eel

    DEFF Research Database (Denmark)

    Butts, Ian; Baeza, R.; Støttrup, Josianne;


    of dietary regime on muscle composition, and liver lipids prior to induced maturation, and the resulting sperm composition and performance. To accomplish this fish were reared on three "enhanced" diets and one commercial diet, each with different levels of fatty acids, arachidonic acid (ARA......), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Neutral lipids from the muscle and liver incorporated the majority of the fatty acid profile, while phospholipids incorporated only certain fatty acids. Diet had an effect on the majority of sperm fatty acids, on the total volume of extractable milt...... induced medium milt volumes but had the highest sperm motility. EPA also seems important for sperm quality parameters since diets with higher EPA percentages had a higher volume of milt and higher sperm motility. In conclusion, dietary fatty acids had an influence on fatty acids in the tissues of male eel...

  4. In vivo and in vitro antıneoplastic actions of caffeic acid phenethyl ester (CAPE): therapeutic perspectives. (United States)

    Akyol, Sumeyya; Ozturk, Gulfer; Ginis, Zeynep; Armutcu, Ferah; Yigitoglu, M Ramazan; Akyol, Omer


    Cancer prevention and treatment strategies have attracted increasing interest. Caffeic acid phenethyl ester (CAPE), an active component of propolis extract, specifically inhibits NF-κB at μM concentrations and shows ability to stop 5-lipoxygenase-catalyzed oxygenation of linoleic acid and arachidonic acid. Previous studies have demonstrated that CAPE exhibits antioxidant, antiinflammatory, antiproliferative, cytostatic, antiviral, antibacterial, antifungal, and, most improtantly, antineoplastic properties. The primary goal of the present review is to summarize and critically evaluate the current knowledge regarding the anticancer effect of CAPE in different cancer types.

  5. Niflumic acid modulates uncoupled substrate-gated conductances in the human glutamate transporter EAAT4. (United States)

    Poulsen, M V; Vandenberg, R J


    1. The effects of niflumic acid on the substrate-gated currents mediated by the glutamate transporter EAAT4 expressed in Xenopus laevis oocytes were examined using radiolabelled substrate flux measurements and two-electrode voltage clamp techniques. 2. Niflumic acid significantly enhanced the substrate-gated currents in EAAT4, without affecting the affinity of the substrates towards EAAT4. At a concentration of 300 microM, niflumic acid caused a 19 +/- 5 % reduction in L-[(3)H]glutamate uptake and no significant effect on the uptake of DL-[(3)H]aspartate. Thus, enhancement of the substrate-gated currents in EAAT4 does not correlate with the rate of substrate transport and suggests that the niflumic acid-induced currents are not thermodynamically coupled to the transport of substrate. 3. Niflumic acid and arachidonic acid co-applied with substrate to EAAT4-expressing oocytes had similar functional consequences. However, niflumic acid still enhanced the L-glutamate-gated current to the same extent in the presence and absence of a saturating dose of arachidonic acid, which suggests that the sites of action of the two compounds are distinct. 4. The EAAT4-mediated currents for the two substrates, L-glutamate and L-aspartate, were not enhanced equally by addition of the same dose of niflumic acid and the ionic composition of the niflumic acid-induced currents was not the same for the two substrates. Protons carry the L-glutamate-gated niflumic acid-induced current and both protons and chloride ions carry the L-aspartate-gated niflumic acid-induced current. 5. These results show that niflumic acid can be used to probe the functional aspects of EAAT4 and that niflumic acid and other non-steroid anti-inflammatory drugs could be used as the basis for the development of novel modulators of glutamate transporters.

  6. Mechanism of cAMP-induced H+ -efflux of Dictyostelium cells: a role for fatty acids

    Indian Academy of Sciences (India)

    H Flaadt; R Schaloske; D Malchow


    Aggregating Dictyostelium cells release protons when stimulated with cAMP. To find out whether the protons are generated by acidic vesicles or in the cytosol, we permeabilized the cells and found that this did not alter the cAMP-response. Proton efflux in intact cells was inhibited by preincubation with the V-type H+ ATPase inhibitor concanamycin A and with the plasma membrane H+ ATPase blocker miconazole. Surprisingly, miconazole also inhibited efflux in permeabilized cells, indicating that this type of H+ ATPase is present on intracellular vesicles as well. Vesicular acidification was inhibited by miconazole and by concanamycin A, suggesting that the acidic vesicles contain both V-type and P-type H+ ATPases. Moreover, concanamycin A and miconazole acted in concert, both in intact cells and in vesicles. The mechanism of cAMP-induced Ca2+-fluxes involves phospholipase A2 activity. Fatty acids circumvent the plasma membrane and stimulate vesicular Ca2+-efflux. Here we show that arachidonic acid elicited H+-efflux not only from intact cells but also from acidic vesicles. The target of regulation by arachidonic acid seemed to be the vesicular Ca2+-relase channel.

  7. Acculturation and Plasma Fatty Acid Concentrations in Hispanic and Chinese-American Adults: The Multi-Ethnic Study of Atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Cassandra S Diep

    Full Text Available Acculturation to the U.S. is associated with increased risk of cardiovascular disease, but the etiologic pathways are not fully understood. Plasma fatty acid levels exhibit ethnic differences and are emerging as biomarkers and predictors of cardiovascular disease risk. Thus, plasma fatty acids may represent one pathway underlying the association between acculturation and cardiovascular disease. We investigated the cross-sectional relationship between acculturation and plasma phospholipid fatty acids in a diverse sample of Hispanic- and Chinese-American adults.Participants included 377 Mexican, 320 non-Mexican Hispanic, and 712 Chinese adults from the Multi-Ethnic Study of Atherosclerosis, who had full plasma phospholipid assays and acculturation information. Acculturation was determined from three proxy measures: nativity, language spoken at home, and years in the U.S., with possible scores ranging from 0 (least acculturated to 5 (most acculturated points. α-Linolenic acid, linoleic acid, eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid were measured in fasting plasma. Linear regression models were conducted in race/ethnicity-stratified analyses, with acculturation as the predictor and plasma phospholipid fatty acids as the outcome variables. We ran secondary analyses to examine associations between acculturation and dietary fatty acids for comparison. Covariates included age, gender, education, and income. Contrary to our hypothesis, no statistically significant associations were detected between acculturation and plasma phospholipid fatty acids for Chinese, non-Mexican Hispanic, or Mexican participants. However, acculturation was related to dietary total n-6 fatty acids and dietary n-3/n-6 ratios in expected directions for Mexican, non-Mexican Hispanic, and combined Hispanic participants. In Chinese individuals, acculturation was unexpectedly associated with lower arachidonic acid intake.Absence of associations between

  8. Eicosapentaenoic Acid Modulates Trichomonas vaginalis Activity. (United States)

    Korosh, Travis; Jordan, Kelsey D; Wu, Ja-Shin; Yarlett, Nigel; Upmacis, Rita K


    Trichomonas vaginalis is a sexually transmitted parasite and, while it is often asymptomatic in males, the parasite is associated with disease in both sexes. Metronidazole is an effective treatment for trichomoniasis, but resistant strains have evolved and, thus, it has become necessary to investigate other possible therapies. In this study, we examined the effects of native and oxidized forms of the sodium salts of eicosapentaenoic, docosahexaenoic, and arachidonic acids on T. vaginalis activity. Eicosapentaenoic acid was the most toxic with 190 and 380 μM causing approximately 90% cell death in Casu2 and ATCC 50142 strains, respectively. In contrast, oxidized eicosapentaenoic acid was the least toxic, requiring > 3 mM to inhibit activity, while low levels (10 μM) were associated with increased parasite density. Mass spectrometric analysis of oxidized eicosapentaenoic acid revealed C20 products containing one to six additional oxygen atoms and various degrees of bond saturation. These results indicate that eicosapentaenoic acid has different effects on T. vaginalis survival, depending on whether it is present in the native or oxidized form. A better understanding of lipid metabolism in T. vaginalis may facilitate the design of synthetic fatty acids that are effective for the treatment of metronidazole-resistant T. vaginalis.

  9. Substrate-selective Inhibition of Cyclooxygeanse-2 by Fenamic Acid Derivatives Is Dependent on Peroxide Tone. (United States)

    Orlando, Benjamin J; Malkowski, Michael G


    Cyclooxygenase-2 (COX-2) catalyzes the oxygenation of arachidonic acid (AA) and endocannabinoid substrates, placing the enzyme at a unique junction between the eicosanoid and endocannabinoid signaling pathways. COX-2 is a sequence homodimer, but the enzyme displays half-of-site reactivity, such that only one monomer of the dimer is active at a given time. Certain rapid reversible, competitive nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to inhibit COX-2 in a substrate-selective manner, with the binding of inhibitor to a single monomer sufficient to inhibit the oxygenation of endocannabinoids but not arachidonic acid. The underlying mechanism responsible for substrate-selective inhibition has remained elusive. We utilized structural and biophysical methods to evaluate flufenamic acid, meclofenamic acid, mefenamic acid, and tolfenamic acid for their ability to act as substrate-selective inhibitors. Crystal structures of each drug in complex with human COX-2 revealed that the inhibitor binds within the cyclooxygenase channel in an inverted orientation, with the carboxylate group interacting with Tyr-385 and Ser-530 at the top of the channel. Tryptophan fluorescence quenching, continuous-wave electron spin resonance, and UV-visible spectroscopy demonstrate that flufenamic acid, mefenamic acid, and tolfenamic acid are substrate-selective inhibitors that bind rapidly to COX-2, quench tyrosyl radicals, and reduce higher oxidation states of the heme moiety. Substrate-selective inhibition was attenuated by the addition of the lipid peroxide 15-hydroperoxyeicosatertaenoic acid. Collectively, these studies implicate peroxide tone as an important mechanistic component of substrate-selective inhibition by flufenamic acid, mefenamic acid, and tolfenamic acid.

  10. Omega-3 Fatty Acids in the Management of Epilepsy. (United States)

    Tejada, Silvia; Martorell, Miquel; Capó, Xavier; Tur, Josep A; Pons, Antoni; Sureda, Antoni


    Omega-3 and omega-6 fatty acids are polyunsaturated fatty acids (PUFAs) with multiple double bonds. Linolenic and alpha-linolenic acids are omega-6 and omega-3 PUFAs, precursors for the synthesis of long-chain PUFAs (LC-PUFAs), such as arachidonic acid (omega-6 PUFA), and eicosapentaenoic and docosahexaenoic acids (omega-3 PUFAs). The three most important omega-3 fatty acids are alpha-linolenic, eicosapentaenoic and docosahexaenoic acids, which cannot be synthesized in enough amounts by the body, and therefore they must be supplied by the diet. Omega-3 fatty acids are essential for the correct functioning of the organism and participate in many physiological processes in the brain. Epilepsy is a common and heterogeneous chronic brain disorder characterized by recurrent epileptic seizures leading to neuropsychiatric disabilities. The prevalence of epilepsy is high achieving about 1% of the general population. There is evidence suggesting that omega-3 fatty acids may have neuroprotective and anticonvulsant effects and, accordingly, may have a potential use in the treatment of epilepsy. In the present review, the potential use of omega-3 fatty acids in the treatment of epilepsy, and the possible proposed mechanisms of action are discussed. The present article summarizes the recent knowledge of the potential protective role of dietary omega-3 fatty acids in epilepsy.

  11. Aspartic acid (United States)

    Aspartic acid is a nonessential amino acids . Amino acids are building blocks of proteins. "Nonessential" means that our ... this amino acid from the food we eat. Aspartic acid is also called asparaginic acid. Aspartic acid helps ...

  12. Baseline plasma fatty acids profile and incident cardiovascular events in the SU.FOL.OM3 trial: the evidence revisited.

    Directory of Open Access Journals (Sweden)

    Léopold K Fezeu

    Full Text Available OBJECTIVE: We aimed to investigate the association between baseline plasma fatty acids profile and the risk of future major cardiovascular events in patients with a history of ischaemic heart disease or ischemic stroke. METHODS: Baseline plasma fatty acids as well as established cardiovascular risk factors were measured in 2,263 patients enrolled in the SUpplementation with FOLate, vitamins B-6 and B-12 and/or OMega-3 fatty acids randomized controlled trial. Incident major cardiovascular, cardiac and cerebrovascular events were ascertained during the 4.7 years of follow up. Hazard ratios were obtained from Cox proportional hazards models after adjustment for cardiovascular risk factors. RESULTS: During the follow-up, 154, 379 and 84 patients had major cardiovascular, cardiac and cerebrovascular events respectively. Upon adjustment for gender, initial event, baseline age and BMI, the risk of developing a major cardiovascular event decreased significantly in successive quartiles of arachidonic acid (P trend<0.002, total omega 3 polyunsaturated fatty acids (P trend<0.03, docosapentaenoic acid (P trend<0.019, docosahexaenoic acid (P trend<0.004, eicosapentaenoic acid + docosahexaenoic acid (P trend<0.03 and eicosapentaenoic acid + docosapentaenoic acid + docosahexaenoic acid (P trend<0.02. This inverse association was borderline significant with increased quartiles of stearidonic acid (P trend<0.06. In the full model, only stearidonic acid remained inversely associated with the risk of developing a major cardiovascular event (P trend<0.035, a cardiac event (P trend<0.016 or a cerebrovascular event (P trend<0.014, while arachidonic acid was inversely associated with the risk a cerebrovascular event (P trend<0.033. CONCLUSION: The inverse association of long chain omega 3 polyunsaturated fatty acids with recurrence of Cardiovascular diseases was mainly driven by well-known cardiovascular risk factors. TRIAL REGISTRATION: ISRCTN

  13. Substrate specificity of the agonist-stimulated release of polyunsaturated fatty acids from vascular endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Rosenthal, M.D.; Garcia, M.C.; Sprecher, H. (Eastern Virginia Medical School, Norfolk (USA))


    Stimulation of vascular endothelial cells with agonists such as histamine and thrombin results in release of arachidonic acid from membrane lipids and subsequent eicosanoid synthesis. As shown previously, the agonist-stimulated deacylation is specific for arachidonate, eicosapentaenoate, and 5,8,11-eicosatrienoate. This study has utilized radiolabeled fatty acids differing in chain length and position of double bonds to further elucidate the fatty acyl specificity of agonist-stimulated deacylation. Replicate wells of confluent human umbilical vein endothelial cells were incubated with 14C-labeled fatty acids and then challenged with histamine, thrombin, or the calcium ionophore A23187. Comparison of the results obtained with isomeric eicosatetraenoic fatty acids with initial double bonds at carbons 4, 5, or 6 indicated that the deacylation induced by all three agonists exhibited marked specificity for the cis-5 double bond. Lack of stringent chain length specificity was indicated by agonist-stimulated release of 5,8,11,14- tetraenoic fatty acids with 18, 19, 20, and 21 carbons. Release of 5,8,14-(14C)eicosatrienoate was two-to threefold that of 5,11,14-(14C)eicosatrienoate, thus indicating that the cis-8 double bond may also contribute to the stringent recognition by the agonist-sensitive phospholipase. The present study has also demonstrated that histamine, thrombin, and A23187 do not stimulate release of docosahexaenoate from endothelial cells.

  14. The natural PPAR agonist linoleic acid stimulated insulin release in the rat pancreas. (United States)

    Lai, Min-Chuan; Teng, Tzu-Hua; Yang, Chi


    Free fatty acids play an important role in regulating animal insulin secretion response. Acute elevated free fatty acids increased animal insulin secretion and glucose-stimulated insulin secretion. In the present study, we perfused the rat pancreas to explore the effect of unsaturated fatty acids on insulin secretion. The results showed that linoleic acid, γ-linolenic acid and arachidonic acid significantly stimulated insulin secretion. Glucose (10 mM) alone induced a biphasic insulin secretion response. The peak effluent insulin concentrations increased by 444% and 800% compared with the baseline in the first and second insulin secretion phases, respectively. Based on comparison of the percentage increases, arachidonic acid, γ-linolenic acid or linoleic acid increased glucose-induced insulin release by 555% and 934%, 522% and 995% and 463% and 1,105% in the first and second insulin secretion phases, respectively. However, the percentage increases of insulin secretion decreased significantly to 402% and 564% in the first and second phases in the rats fed a high-fat diet for 13 weeks. Linoleic acid alone stimulated a 391% increase in the peak insulin concentration compared with the baseline in the rats fed a normal diet. The peak insulin concentration decreased significantly to 183% in the rats fed a long-term high-fat diet. All the results suggested that unsaturated fatty acids stimulated insulin secretion and additively increased glucose-induced insulin secretion in the perfused rat pancreas. However, the rats fed a high-fat diet had a decreased linoleic acid-induced insulin secretion response.

  15. EETs mediate cardioprotection of salvianolic acids through MAPK signaling pathway

    Directory of Open Access Journals (Sweden)

    Shoubao Wang


    Full Text Available Salvianolic acids, including salvianolic acid A (SAA and salvianolic acid B (SAB, are the main water-soluble bioactive compounds isolated from the Chinese medicinal herb Danshen and have been shown to exert in vitro and in vivo cardiovascular protection. Recent studies suggest that epoxyeicosatrienoic acids (EETs, the primary cytochrome P450 2J (CYP2J epoxygenase metabolites of arachidonic acid, are involved in the progression of ischemic injury in diverse organs. Here, we investigated the relation between the protective effects of salvianolic acids and EETs/sEH as well as MAPK signaling pathway. In the present study, the rat acute myocardial infarction (AMI model was established by the left anterior descending coronary artery occlusion. Our results showed that salvianolic acids significantly reduced ST-segment elevation and serum levels of CK-MB, LDH, and ALT in AMI rats, and significantly attenuated the caspase 3 expression and reduced the ratio of Bax/Bcl-2. ELISA measurement showed that salvianolic acids significantly increased the 14,15-EET levels in blood and heart, and attenuated hydrolase activity of sEH in heart of AMI rat. Western blotting analysis suggested that salvianolic acids significantly attenuated the phosphorylation of JNK and p38, and increased phosphorylation of ERK in heart. In conclusion, these results indicate that EETs/sEH and MAPK signaling pathways are important processes in cardioprotection of salvianolic acids.

  16. [Effect of acute stress on the fatty acid composition of lipids of adrenal and heart mitochondria in rabbits]. (United States)

    Mandrik, K A; Doroshkevich, N A; Buko, V U; Vinogradov, V V


    A comparative study of changes in the fatty acid composition of rabbit heart and adrenal mitochondria was carried out after acute (1h) immobilization stress. In heart mitochondria the stress induced a decrease in the content of capric, lauric, myristic and pentadecanic acids. A statistically significant reduction of the amount of heptadecanoic, linoleic, arachidonic acids and an increase in the level of palmitic acid was noted in adrenal mitochondria. The acute stress resulted in differently directed shifts in the saturation of fatty acids. An elevation of the sum of unsaturated fatty acids was observed in the heart, and a decrease was detected in the adrenal glands. The above shifts in the fatty acid composition of adrenal and heart mitochondria provide evidence for different directions of lipid metabolism in these organs following stress.

  17. Effects of dietary fatty acids on the production and quality of eggs and larvae of Atlantic cod (Gadus morhua L.)

    DEFF Research Database (Denmark)

    Røjbek, Maria; Støttrup, Josianne; Jacobsen, Charlotte;


    Cultivated Atlantic cod (Gadus morhua) entering their first year of gamete maturation were fed diets with different levels of arachidonic acid (ARA) and eicosapentaenoic acid (EPA) for 6.5 months prior to commencement of spawning. Gravid females were stripped three times: at the beginning, peak...... and end of spawning. Lipid composition and egg and larval quality of 34 family crosses were investigated. Results indicated that ARA uptake into eggs from broodstock diet was highly efficient achieving proportions of ARA up to 84% higher in eggs than in the diet. EPA was 42–76% higher, and DHA was 155...

  18. Chemical Composition and Fatty Acids of Glodok Fish by High Thermal Processing

    Directory of Open Access Journals (Sweden)

    Sri Purwaningsih


    Full Text Available Glodok is an economically underrated fish with a high nutrient content. The research aims to study the changes on chemical composition, fatty acids, omega-6 and omega-3 ratio in glodok muscle after processing with different methods of boiling, steaming, and boiling with addition of salt (3%. The results showed that the treatment (boiling, steaming, and boiling with addition of salt gives a significant effect (α=0.05 in water content, ash, lipid content, nervonat acid, linoleic acid, arachidonic acid, EPA, and DHA. The best processing method was steaming. The ratio of omega-3 and omega-6 in fresh glodok fish was 2,1:1, which is higher than WHO recommendation of 0,6:1,7.Keywords: chemical composition, fatty acid, glodok fish, processing

  19. Inhibition of in vitro cholesterol synthesis by fatty acids. (United States)

    Kuroda, M; Endo, A


    Inhibitory effect of 44 species of fatty acids on cholesterol synthesis has been examined with a rat liver enzyme system. In the case of saturated fatty acids, the inhibitory activity increased with chain length to a maximum at 11 to 14 carbons, after which activity decreased rapidly. The inhibition increased with the degree of unsaturation of fatty acids. Introduction of a hydroxy group at the alpha-position of fatty acids abolished the inhibition, while the inhibition was enhanced by the presence of a hydroxy group located in an intermediate position of the chain. Branched chain fatty acids having a methyl group at the terminal showed much higher activity than the corresponding saturated straight chain fatty acids with the same number of carbons. With respect to the mechanism for inhibition, tridecanoate was found to inhibit acetoacetyl-CoA thiolase specifically without affecting the other reaction steps in the cholesterol synthetic pathway. The highly unsaturated fatty acids, arachidonate and linoleate, were specific inhibitors of 3-hydroxy-3-methyl-glutaryl-CoA synthase. On the other hand, ricinoleate (hydroxy acid) and phytanate (branched-chain acid) diminished the conversion of mevalonate to sterols by inhibiting a step or steps between squalene and lanosterol.

  20. Acetic acid in aged vinegar affects molecular targets for thrombus disease management. (United States)

    Jing, Li; Yanyan, Zhang; Junfeng, Fan


    To elucidate the mechanism underlying the action of dietary vinegar on antithrombotic activity, acetic acid, the main acidic component of dietary vinegar, was used to determine antiplatelet and fibrinolytic activity. The results revealed that acetic acid significantly inhibits adenosine diphosphate (ADP)-, collagen-, thrombin-, and arachidonic acid (AA)-induced platelet aggregation. Acetic acid (2.00 mM) reduced AA-induced platelet aggregation to approximately 36.82 ± 1.31%, and vinegar (0.12 mL L(-1)) reduced the platelet aggregation induced by AA to 30.25 ± 1.34%. Further studies revealed that acetic acid exerts its effects by inhibiting cyclooxygenase-1 and the formation of thromboxane-A2. Organic acids including acetic acid, formic acid, lactic acid, citric acid, and malic acid also showed fibrinolytic activity; specifically, the fibrinolytic activity of acetic acid amounted to 1.866 IU urokinase per mL. Acetic acid exerted its fibrinolytic activity by activating plasminogen during fibrin crossing, thus leading to crosslinked fibrin degradation by the activated plasmin. These results suggest that organic acids in dietary vinegar play important roles in the prevention and cure of cardiovascular diseases.

  1. Polyunsaturated fatty acids and inflammatory diseases. (United States)

    Gil, A


    Inflammation is overall a protective response, whose main goal is to liberate the human being of cellular lesions caused by micro-organisms, toxins, allergens, etc., as well as its consequences, and of death cells and necrotic tissues. Chronic inflammation, which is detrimental to tissues, is the basic pathogenic mechanism of hypersensitivity reactions against xenobiotics. Other frequent pathologies, for instance atherosclerosis, chronic hepatitis, inflammatory bowel disease (IBD), liver cirrhosis, lung fibrosis, psoriasis, and rheumatoid arthritis are also chronic inflammatory diseases. Chemical mediators of inflammation are derived from blood plasma or different cell-type activity. Biogenic amines, eicosanoids and cytokines are within the most important mediators of inflammatory processes. The different activities of eicosanoids derived from arachidonic acid (20:4 n-6) versus those derived from eicosapentaenoic acid (20:5 n-3) are one of the most important mechanisms to explain why n-3, or omega-3, polyunsaturated fatty acids (PUFA) exhibit anti-inflammatory properties in many inflammatory diseases. Dietary supplements ranging 1-8 g per day of n-3 PUFA have been reportedly beneficial in the treatment of IBD, eczema, psoriasis and rheumatoid arthritis. In addition, recent experimental studies in rats with experimental ulcerative colitis, induced by intrarectal injection of trinitrobenzene sulphonic acid, have documented that treatment with n-3 long-chain PUFA reduces mucosal damage as assessed by biochemical and histological markers of inflammation. Moreover, the defence antioxidant system in this model is enhanced in treated animals, provided that the n-3 PUFA supply is adequately preserved from oxidation.

  2. The fatty acid compositions of predator Piocoris luridus (Heteroptera: Lygaeidae) and its host Monosteria unicostata (Heteroptera: Tingidae) reared on almond

    Institute of Scientific and Technical Information of China (English)



    The changes in fatty acid compositions during nutritional interaction among almond Amygdalus communis Linnaeus (Rosales: Rosaceae) (host plant), lacebug Monosteria unicostata (Mulsant and Rey) (Heteroptera: Tingidae) and its predator Piocoris luridus Fieber (Heteroptera: Lygaeidae) were determined by gas chromatography and gas chroma-tography-mass spectrometry analyses. The fatty acid profiles of phospholipids and triacylglycerols were substantially different. Unlike the general observations for virtually most terrestrial insects, arachidonic and eicosapentaenoic acids were detected in high proportions of phospholipid fractions in both insects, especially in P.luridus.Also the almond tissues provide very little oleic acid to the herbivore diet, yet both insect species developed high proportions of this component. Our data reveals instances of specific accumulation of fatty acid biosynthesis, elongation/desaturation, and not incorporating selected fatty acids into cellular lipids.

  3. A diet high in α-linolenic acid and monounsaturated fatty acids attenuates hepatic steatosis and alters hepatic phospholipid fatty acid profile in diet-induced obese rats. (United States)

    Hanke, Danielle; Zahradka, Peter; Mohankumar, Suresh K; Clark, Jaime L; Taylor, Carla G


    This study investigated the efficacy of the plant-based n-3 fatty acid, α-linolenic acid (ALA), a dietary precursor of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for modulating hepatic steatosis. Rats were fed high fat (55% energy) diets containing high oleic canola oil, canola oil, a canola/flax oil blend (C/F, 3:1), safflower oil, soybean oil, or lard. After 12 weeks, C/F and weight-matched (WM) groups had 20% less liver lipid. Body mass, liver weight, glucose and lipid metabolism, inflammation and molecular markers of fatty acid oxidation, synthesis, desaturation and elongation did not account for this effect. The C/F group had the highest total n-3 and EPA in hepatic phospholipids (PL), as well as one of the highest DHA and lowest arachidonic acid (n-6) concentrations. In conclusion, the C/F diet with the highest content of the plant-based n-3 ALA attenuated hepatic steatosis and altered the hepatic PL fatty acid profile.

  4. Relationship between Fecal Content of Fatty Acids and Cyclooxygenase mRNA Expression and Fatty Acid Composition in Duodenal Biopsies, Serum Lipoproteins, and Dietary Fat in Colectomized Familial Adenomatous Polyposis Patients

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    K. Almendingen


    Full Text Available A few familial adenomatous polyposis studies have focused upon faecal sterols and bile acids but none has analysed the fecal content of fatty acids. We report here findings of an observational study on 29 colectomized familial adenomatous polyposis patients that describe the fecal content of fatty acids, and relate this to the proportions of fatty acids and levels of cyclooxygenase mRNA expression in duodenal biopsies, levels of serum lipoproteins, and diet. In the ileostomy group separately (n=12, the fecal content of arachidonic acid was correlated negatively to the proportions of eicosapentaenoic acid and docosahexaenoic acid in duodenal biopsies. Total serum-cholesterol was negatively correlated to the fecal content of saturates and monounsaturates. The fecal palmitoleic acid/palmitic acid ratio was positively correlated to the levels of cyclooxygease-2 expression in duodenal biopsies.In the ileal-pouch-anal anastomosis group separately (n=17, significant correlations were found between the fecal contents of oleic acid, linoleic acid, and alpha-linolenic acid, and the proportions of myristic acid, oleic acid and eicosaenoic acid in duodenal biopsies. Dietary monounsaturates were positively correlated to different fecal fatty acids. Future studies should focus on molecular mechanisms relevant to fatty acid metabolism, inflammation, and angiogenesis, in addition to nutrition.

  5. Effects of Oils Rich in Linoleic and α-Linolenic Acids on Fatty Acid Profile and Gene Expression in Goat Meat

    Directory of Open Access Journals (Sweden)

    Mahdi Ebrahimi


    Full Text Available Alteration of the lipid content and fatty acid (FA composition of foods can result in a healthier product. The aim of this study was to determine the effect of flaxseed oil or sunflower oil in the goat diet on fatty acid composition of muscle and expression of lipogenic genes in the semitendinosus (ST muscle. Twenty-one entire male Boer kid goats were fed diets containing different levels of linoleic acid (LA and α-linolenic acid (LNA for 100 days. Inclusion of flaxseed oil increased (p < 0.05 the α-linolenic acid (C18:3n-3 concentration in the ST muscle. The diet high in α-linolenic acid (p < 0.05 decreased the arachidonic acid (C20:4n-6 and conjugated linolenic acid (CLA c-9 t-11 content in the ST muscle. There was a significant (p < 0.05 upregulation of PPARα and PPARγ gene expression and downregulation of stearoyl-CoA desaturase (SCD gene in the ST muscle for the high α-linolenic acid group compared with the low α-linolenic acid group. The results of the present study show that flaxseed oil as a source of α-linolenic acid can be incorporated into the diets of goats to enrich goat meat with n-3 fatty acids, upregulate the PPARα and PPARγ, and downregulate the SCD gene expression.

  6. Occurrence of high levels of tetracosahexaenoic acid in the jellyfish Aurelia sp. (United States)

    Nichols, Peter D; Danaher, Kathryn T; Koslow, J Anthony


    The FA composition of the pelagic jellyfish Aurelia sp. collected from off-shore Western Australia waters was determined by capillary GC and GC-MS, with confirmation of PUFA structure performed by analysis of 4,4-dimethyloxazoline derivatives. PUFA constituted 47.6% of the total FA, with the essential PUFA eicosapentaenoic acid (EPA), arachidonic acid, and DHA accounting for 34%. Of particular interest, the unusual very long chain PUFA 6,9,12,15,18,21-tetracosahexaenoic acid (THA, 24:6n-3) was present at 9.3%, and the rarely reported 6,9,12,15,18-tetracosapentaenoic acid (24:5n-6) also was detected at 0.8%. To our knowledge, this represents the first report of THA as a major PUFA in a pelagic marine organism.

  7. Dietary (n-3)-fatty acids, prostaglandins, and prolonged gestation in humans

    DEFF Research Database (Denmark)

    Hansen, Harald S.; Olsen, S.F.


    Prostaglandins, especially prostaglandin F2 alpha, are important regulators in the onset and maintenance of parturition in humans. Inhibition of prostaglandin formation by drugs can prolong gestation in humans. High dietary intake of long chain (n-3)-fatty acids can inhibit formation of many...... arachidonic acid-derived prostaglandins as well as stimulate formation of eicosapentaenoic acid-derived prostaglandins. The latter ones often have lower biological activity than the former ones. The effect of (n-3)-fatty acids on prostaglandin formation has been shown by analysis of prostaglandin metabolites...... in human urine. Very little is known about the tissue origin as well as the physiologicalfunctions of those prostaglandins, the metabolites of which are quantitated in urine from non-pregnant humans. In pregnant women the increased amount of prostaglandin F2 alpha-metabolites in urine, plasma and amniotic...

  8. Eccentric contractions affect muscle membrane phospholipid fatty acid composition in rats

    DEFF Research Database (Denmark)

    Helge, Jørn Wulff; Therkildsen, K J; Jørgensen, T B


    This study investigated if prior eccentric contractions, and thus mechanical strain and muscle damage, exert an effect on the muscle membrane phospholipid fatty acid composition in rats, and whether a possible effect could be attenuated by dietary supplements. Twenty-three rats were randomised...... to three groups who received chow with added fish oil (n = 8), vitamin C (n = 8) or no supplement (n = 7). After 3 weeks of feeding, calf muscles on one side were stimulated electrically during anaesthesia causing eccentric contractions. Two days later the white gastrocnemius, a part of the stimulated calf...... muscle, was excised from both legs. In the muscles stimulated to contract eccentrically, compared to the control muscles, the proportion of arachidonic acid, C20:4,n-6 (17.7 +/- 0.6; 16.4 +/- 0.4% of total fatty acids, respectively) and docosapentanoeic acid, C22:5,n-3 (2.9 +/- 0.1 and 2.7 +/- 0...

  9. Effect of low temperature on highly unsaturated fatty acid biosynthesis in activated sludge. (United States)

    He, Su; Ding, Li-Li; Xu, Ke; Geng, Jin-Ju; Ren, Hong-Qiang


    Low temperature is a limiting factor for the microbial activity of activated sludge for sewage treatment plant in winter. Highly unsaturated fatty acid (UFA) biosynthesis, phospholipid fatty acid (PLFA) constituents and microbial structure in activated sludge at low temperature were investigated. Over 12 gigabases of metagenomic sequence data were generated with the Illumina HiSeq 2000 platform. The result showed 43.11% of phospholipid fatty acid (PLFA) in the activated sludge participated in UFA biosynthesis, and γ-Linolenic could be converted to Arachidonic acid at low temperature. The highly UFA biosynthesis in activated sludge was n-6 highly UFA biosynthesis, rather than n-3 highly UFA biosynthesis. The microbial community structures of activated sludge were analyzed by PLFA and high-throughput sequencing (HiSeq) simultaneously. Acidovorax, Pseudomonas, Flavobacterium and Polaromonas occupied higher percentage at 5°C, and genetic changes of highly UFA biosynthesis derived from microbial community structures change.

  10. Polyunsaturated fatty acid metabolites as novel lipidomic biomarkers for noninvasive diagnosis of nonalcoholic steatohepatitis. (United States)

    Loomba, Rohit; Quehenberger, Oswald; Armando, Aaron; Dennis, Edward A


    Lipotoxicity is a key mechanism thought to be responsible for the progression of nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). Noninvasive diagnosis of NASH is a major unmet clinical need, and we hypothesized that PUFA metabolites, in particular arachidonic acid (AA)-derived eicosanoids, in plasma would differentiate patients with NAFL from those with NASH. Therefore, we aimed to assess the differences in the plasma eicosanoid lipidomic profile between patients with biopsy-proven NAFL versus NASH versus normal controls without nonalcoholic fatty liver disease (NAFLD; based on MRI fat fraction eicosanoid and other PUFA metabolite levels between NAFL versus NASH versus normal controls. Utilizing a uniquely well-characterized cohort, we demonstrated that plasma eicosanoid and other PUFA metabolite profiling can differentiate between NAFL and NASH. The top candidate as a single biomarker for differentiating NAFL from NASH was 11,12-dihydroxy-eicosatrienoic acid (11,12-diHETrE) with an area under the receiver operating characteristic curve (AUROC) of 1. In addition, we also found a panel including 13,14-dihydro-15-keto prostaglandin D2 (dhk PGD2) and 20-carboxy arachidonic acid (20-COOH AA) that demonstrated an AUROC of 1. This proof-of-concept study provides early evidence that 11,12-diHETrE, dhk PGD2, and 20-COOH AA are the leading eicosanoid candidate biomarkers for the noninvasive diagnosis of NASH.

  11. 15-lipoxygenase metabolites of docosahexaenoic acid inhibit prostate cancer cell proliferation and survival.

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    Joseph T O'Flaherty

    Full Text Available A 15-LOX, it is proposed, suppresses the growth of prostate cancer in part by converting arachidonic, eicosatrienoic, and/or eicosapentaenoic acids to n-6 hydroxy metabolites. These metabolites inhibit the proliferation of PC3, LNCaP, and DU145 prostate cancer cells but only at ≥1-10 µM. We show here that the 15-LOX metabolites of docosahexaenoic acid (DHA, 17-hydroperoxy-, 17-hydroxy-, 10,17-dihydroxy-, and 7,17-dihydroxy-DHA inhibit the proliferation of these cells at ≥0.001, 0.01, 1, and 1 µM, respectively. By comparison, the corresponding 15-hydroperoxy, 15-hydroxy, 8,15-dihydroxy, and 5,15-dihydroxy metabolites of arachidonic acid as well as DHA itself require ≥10-100 µM to do this. Like DHA, the DHA metabolites a induce PC3 cells to activate a peroxisome proliferator-activated receptor-γ (PPARγ reporter, express syndecan-1, and become apoptotic and b are blocked from slowing cell proliferation by pharmacological inhibition or knockdown of PPARγ or syndecan-1. The DHA metabolites thus slow prostate cancer cell proliferation by engaging the PPARγ/syndecan-1 pathway of apoptosis and thereby may contribute to the prostate cancer-suppressing effects of not only 15-LOX but also dietary DHA.

  12. Conversion of α-linolenic acid to long-chain omega-3 fatty acid derivatives and alterations of HDL density subfractions and plasma lipids with dietary polyunsaturated fatty acids in Monk parrots (Myiopsitta monachus). (United States)

    Petzinger, C; Larner, C; Heatley, J J; Bailey, C A; MacFarlane, R D; Bauer, J E


    The effect of α-linolenic acid from a flaxseed (FLX)-enriched diet on plasma lipid and fatty acid metabolism and possible atherosclerosis risk factors was studied in Monk parrots (Myiopsitta monachus). Twenty-four Monk parrots were randomly assigned to diets containing either 10% ground SUNs or 10% ground FLXs. Feed intake was calculated daily. Blood samples, body condition scores and body weights were obtained at -5 weeks, day 0, 7, 14, 28, 42 and 70. Plasma samples were analysed for total cholesterol, free cholesterol, triacylglycerols and lipoproteins. Phospholipid subfraction fatty acid profiles were determined. By day 70, the FLX group had significantly higher plasma phospholipid fatty acids including 18:3n-3 (α-linolenic acid), 20:5n-3 (eicosapentaenoic acid) and 22:6n-3 (docosahexaenoic acid). The sunflower group had significantly higher plasma phospholipid levels of 20:4n-6 (arachidonic acid). By day 70, the high-density lipoprotein (HDL) peak shifted resulting in significantly different HDL peak densities between the two experimental groups (1.097 g/ml FLX group and 1.095 g/ml SUN group, p = 0.028). The plasma fatty acid results indicate that Monk parrots can readily convert α-linolenic acid to the long-chain omega-3 derivatives including docosahexaenoic acid and reduce 20:4n-6 accumulation in plasma phospholipids. The reason for a shift in the HDL peak density is unknown at this time.

  13. Active ingredients fatty acids as antibacterial agent from the brown algae Padina pavonica and Hormophysa triquetra

    Institute of Scientific and Technical Information of China (English)

    Gihan Ahmed El Shoubaky; Essam Abd El Rahman Salem


    Objective: To estimate the fatty acids content in the brown algae Padina pavonica (P. pavonica) and Hormophysa triquetra (H. triquetra) and evaluate their potential antimicrobial activity as bioactive compounds.Methods:The fatty acid compositions of the examined species were analyzed using gas chromatography-mass spectrometry. The antimicrobial activity of crude and fatty acids was assessed using the agar plug technique.Results:The fatty acids profile ranged from C8:0 to C20:4. Concentration of saturated fatty acids in P. pavonica was in the order palmitic>myristic>stearic whereas concentration of the unsaturated fatty acids was oleic acid>palmitoleic>9-cis-hexadecenoic>linoleic acid>α-linolenic>arachidonic> elaidic acid. H. triquetra contained high concentration of saturated fatty acids than those of P. pavonica which was in the order as follows: palmitic>margaric>myristic>nonadecyclic>stearic>caprylic>tridecylic>pentadecylic>lauric while the unsaturated fatty acids consisted of oleic>nonadecenoic>non adecadienoate>margaroleic. The crude and fatty acid extracts of H. triquetra and P. pavonica were biologically active on the tested pathogens. H.triquetra exhibited a larger inhibitory zone than P. pavonica. Conclusions: The brown algae P. pavonica and H. triquetra have high efficient amount of fatty acids and showed strong antibacterial activity, especially H. triquetra.

  14. Influence of vitamin E on the antiplatelet effect of acetylsalicylic acid in human blood. (United States)

    González-Correa, J A; Arrebola, M M; Guerrero, A; Muñoz-Marín, J; Ruiz-Villafranca, D; Sánchez de La Cuesta, F; De La Cruz, J P


    We analysed the in vitro interaction between acetylsalicylic acid and vitamin E on the principal antiplatelet sites of action of acetylsalicylic acid, i.e., platelet aggregation, prostanoid production in platelets and leukocytes, and nitric oxide synthesis. Aggregation was measured in whole blood and in platelet-rich plasma (PRP) with ADP, collagen or arachidonic acid as platelet inducers, and we measured the production of thromboxane B2, prostacyclin and nitric oxide. Vitamin E potentiated the antiplatelet effect of acetylsalicylic acid in both whole blood and PRP. In PRP induced with collagen the IC50 for acetylsalicylic acid alone was 339+/-11.26, and that of acetylsalicylic acid+vitamin E was 0.89+/-0.09 (Pacetylsalicylic acid. Vitamin E spared or even increased prostacyclin levels, and acetylsalicylic acid+vitamin E diminished the inhibition of prostacyclin synthesis by acetylsalicylic acid (IC50 acetylsalicylic acid alone=1.81+/-0.15 microM; IC50 acetylsalicylic acid+vitamin E= 12.92+/-1.10 microM, Pacetylsalicylic acid on neutrophil nitric oxide production 42-fold (Pacetylsalicylic acid in vitro, and thus merits further research in ex vivo studies.

  15. Serum Fatty Acids Are Correlated with Inflammatory Cytokines in Ulcerative Colitis.

    Directory of Open Access Journals (Sweden)

    Dawn M Wiese

    Full Text Available Ulcerative colitis (UC is associated with increased dietary intake of fat and n-6 polyunsaturated fatty acids (PUFA. Modification of fat metabolism may alter inflammation and disease severity. Our aim was to assess differences in dietary and serum fatty acid levels between control and UC subjects and associations with disease activity and inflammatory cytokines.Dietary histories, serum, and colonic tissue samples were prospectively collected from 137 UC subjects and 38 controls. Both histologic injury and the Mayo Disease Activity Index were assessed. Serum and tissue cytokines were measured by Luminex assay. Serum fatty acids were obtained by gas chromatography.UC subjects had increased total fat and oleic acid (OA intake, but decreased arachidonic acid (AA intake vs controls. In serum, there was less percent saturated fatty acid (SFA and AA, with higher monounsaturated fatty acids (MUFA, linoleic acid, OA, eicosapentaenoic acid (EPA, and docosapentaenoic acid (DPA in UC. Tissue cytokine levels were directly correlated with SFA and inversely correlated with PUFA, EPA, and DPA in UC subjects, but not controls. 5-aminosalicylic acid therapy blunted these associations.In summary, we found differences in serum fatty acids in UC subjects that correlated with pro-inflammatory tissue cytokines. We propose that fatty acids may affect cytokine production and thus be immunomodulatory in UC.

  16. Metabolomics of dietary fatty acid restriction in patients with phenylketonuria.

    Directory of Open Access Journals (Sweden)

    Ulrike Mütze

    Full Text Available BACKGROUND: Patients with phenylketonuria (PKU have to follow a lifelong phenylalanine restricted diet. This type of diet markedly reduces the intake of saturated and unsaturated fatty acids especially long chain polyunsaturated fatty acids (LC-PUFA. Long-chain saturated fatty acids are substrates of mitochondrial fatty acid oxidation for acetyl-CoA production. LC-PUFA are discussed to affect inflammatory and haemostaseological processes in health and disease. The influence of the long term PKU diet on fatty acid metabolism with a special focus on platelet eicosanoid metabolism has been investigated in the study presented here. METHODOLOGY/PRINCIPAL FINDINGS: 12 children with PKU under good metabolic control and 8 healthy controls were included. Activated fatty acids (acylcarnitines C6-C18 in dried blood and the cholesterol metabolism in serum were analyzed by liquid chromatographic tandem mass spectrometry (LC-MS/MS. Fatty acid composition of plasma glycerophospholipids was determined by gas chromatography. LC-PUFA metabolites were analyzed in supernatants by LC-MS/MS before and after platelet activation and aggregation using a standardized protocol. Patients with PKU had significantly lower free carnitine and lower activated fatty acids in dried blood compared to controls. Phytosterols as marker of cholesterol (re- absorption were not influenced by the dietary fatty acid restriction. Fatty acid composition in glycerophospholipids was comparable to that of healthy controls. However, patients with PKU showed significantly increased concentrations of y-linolenic acid (C18:3n-6 a precursor of arachidonic acid. In the PKU patients significantly higher platelet counts were observed. After activation with collagen platelet aggregation and thromboxane B(2 and thromboxane B(3 release did not differ from that of healthy controls. CONCLUSION/SIGNIFICANCE: Long-term dietary fatty acid restriction influenced the intermediates of mitochondrial beta

  17. Combined Effects of Ocean Warming and Acidification on Copepod Abundance, Body Size and Fatty Acid Content.

    Directory of Open Access Journals (Sweden)

    Jessica Garzke

    Full Text Available Concerns about increasing atmospheric CO2 concentrations and global warming have initiated studies on the consequences of multiple-stressor interactions on marine organisms and ecosystems. We present a fully-crossed factorial mesocosm study and assess how warming and acidification affect the abundance, body size, and fatty acid composition of copepods as a measure of nutritional quality. The experimental set-up allowed us to determine whether the effects of warming and acidification act additively, synergistically, or antagonistically on the abundance, body size, and fatty acid content of copepods, a major group of lower level consumers in marine food webs. Copepodite (developmental stages 1-5 and nauplii abundance were antagonistically affected by warming and acidification. Higher temperature decreased copepodite and nauplii abundance, while acidification partially compensated for the temperature effect. The abundance of adult copepods was negatively affected by warming. The prosome length of copepods was significantly reduced by warming, and the interaction of warming and CO2 antagonistically affected prosome length. Fatty acid composition was also significantly affected by warming. The content of saturated fatty acids increased, and the ratios of the polyunsaturated essential fatty acids docosahexaenoic- (DHA and arachidonic acid (ARA to total fatty acid content increased with higher temperatures. Additionally, here was a significant additive interaction effect of both parameters on arachidonic acid. Our results indicate that in a future ocean scenario, acidification might partially counteract some observed effects of increased temperature on zooplankton, while adding to others. These may be results of a fertilizing effect on phytoplankton as a copepod food source. In summary, copepod populations will be more strongly affected by warming rather than by acidifying oceans, but ocean acidification effects can modify some temperature impacts.

  18. Combined Effects of Ocean Warming and Acidification on Copepod Abundance, Body Size and Fatty Acid Content (United States)

    Hansen, Thomas; Ismar, Stefanie M. H.; Sommer, Ulrich


    Concerns about increasing atmospheric CO2 concentrations and global warming have initiated studies on the consequences of multiple-stressor interactions on marine organisms and ecosystems. We present a fully-crossed factorial mesocosm study and assess how warming and acidification affect the abundance, body size, and fatty acid composition of copepods as a measure of nutritional quality. The experimental set-up allowed us to determine whether the effects of warming and acidification act additively, synergistically, or antagonistically on the abundance, body size, and fatty acid content of copepods, a major group of lower level consumers in marine food webs. Copepodite (developmental stages 1–5) and nauplii abundance were antagonistically affected by warming and acidification. Higher temperature decreased copepodite and nauplii abundance, while acidification partially compensated for the temperature effect. The abundance of adult copepods was negatively affected by warming. The prosome length of copepods was significantly reduced by warming, and the interaction of warming and CO2 antagonistically affected prosome length. Fatty acid composition was also significantly affected by warming. The content of saturated fatty acids increased, and the ratios of the polyunsaturated essential fatty acids docosahexaenoic- (DHA) and arachidonic acid (ARA) to total fatty acid content increased with higher temperatures. Additionally, here was a significant additive interaction effect of both parameters on arachidonic acid. Our results indicate that in a future ocean scenario, acidification might partially counteract some observed effects of increased temperature on zooplankton, while adding to others. These may be results of a fertilizing effect on phytoplankton as a copepod food source. In summary, copepod populations will be more strongly affected by warming rather than by acidifying oceans, but ocean acidification effects can modify some temperature impacts. PMID:27224476

  19. Effects of Different High Fat Diets on Fatty Acid Composition of Skeletal Muscle and Liver in Nude Mice Bearing Pancreatic Cancer

    Institute of Scientific and Technical Information of China (English)

    Yi-jie DUAN; Feng WANG; Zhong-wen LIU; Ming YU


    Objective To investigate the impacts of different dietary fatty acids on fatty acid composition in skeletal muscle and liver in nude mice bearing pancreatic cancer.MethodsSixty C57BL/6 nude mice were randomly divided into 6 groups: saturated fatty acid-fed group (SFA group), monounsaturated fatty acid-fed group (MUFA group), n-6 polyunsaturated fatty acid-fed group (n-6 PUFA group), n-3 polyunsaturated fatty acid-fed group (n-3 PUFA group), iso-caloric control (ISO-C) and normal control (NC). Four high fat diets containing 15% oils derived from coconut (SFA group), olive (MUFA group), soybean (n-6 PUFA group) andflaxseed (n-3 PUFA group) respectively, were prepared. ISO-C and NC groups were fed diet containing 4%-5% soybean oil. After one week of feeding, HPAF-Ⅱ human pancreatic cancer cells were transplanted orthotopically. The mice were fed corresponding diets in the following 14 weeks and then sacrificed. Skeletal muscle and liver tissues were sampled. Fatty acids in the samples were analyzed by gas chromatography-mass spectrometry.ResultsFatty acid composition of skeletal muscle and liver were similar between ISO-C group and NC group.Compared to ISO-C group, the contents of fatty acids in skeletal muscle were: (1) palmitic acid (C16:0), hepentadecane acid (C17:0), stearic acid (C18:0) and arachidonic acid (C20:0) increased inSFA group (P< 0.05); (2)oleic acid (C18:1) increased in MUFA group (P< 0.05); (3)γ-linolenic acid (γ-C18:3) increased in n-6 PUFA group (P<0.05);(4) linolenic acid (C18:3), eicosapentaenoic acid (C20:5) and clupanodonic acid (C22:5) increased in n-3 PUFA group (P<0.05). In the liver, the contents of fatty acids were: (1) saturated fatty acids not increased in SFA group; (2) eicosenoic acid (C20:1) increased in MUFA group (P< 0.05); (3) eicosadienoic acid (C20:2) and arachidonic acid (C20:4) increased in n-6 PUFA group (P < 0.05); (4) linolenic acid, eicosapentaenoic acid, clupanodonic acid and docosahexaenoic acid increased in n-3 PUFA

  20. Effect of dietary fatty acid intake on prospective weight change in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition

    DEFF Research Database (Denmark)

    Nimptsch, Katharina; Berg-Beckhoff, Gabi; Linseisen, Jakob


    OBJECTIVE: To evaluate the association between fatty acid (alpha-linolenic acid (ALA), EPA, DHA, palmitic, stearic, oleic, linoleic and arachidonic acids) intake and prospective weight change in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition. DESIGN......) and categorised into four groups (weight loss, or =2.5 to or =7.5%/5 years). Energy-adjusted dietary fatty acid intake data were estimated from the FFQ completed at baseline. Multivariate linear regression models as well as multinomial logistic regression analyses (carbohydrate replacement models) were conducted....... RESULTS: Stearic acid intake was linearly associated with weight gain (P acid intake, significantly so in women. In multinomial models, women in the highest tertile of ALA and stearic acid intake showed increased OR (95 % CI...

  1. Modifications of proteins by polyunsaturated fatty acid peroxidation products (United States)

    Refsgaard, Hanne H. F.; Tsai, Lin; Stadtman, Earl R.


    The ability of unsaturated fatty acid methyl esters to modify amino acid residues in bovine serum albumin (BSA), glutamine synthetase, and insulin in the presence of a metal-catalyzed oxidation system [ascorbate/Fe(III)/O2] depends on the degree of unsaturation of the fatty acid. The fatty acid-dependent generation of carbonyl groups and loss of lysine residues increased in the order methyl linoleate < methyl linolenate < methyl arachidonate. The amounts of alkyl hydroperoxides, malondialdehyde, and a number of other aldehydes that accumulated when polyunsaturated fatty acids were oxidized in the presence of BSA were significantly lower than that observed in the absence of BSA. Direct treatment of proteins with various lipid hydroperoxides led to a slight increase in the formation of protein carbonyl derivatives, whereas treatment with the hydroperoxides together with Fe(II) led to a substantial increase in the formation of protein carbonyls. These results are consistent with the proposition that metal-catalyzed oxidation of polyunsaturated fatty acids can contribute to the generation of protein carbonyls by direct interaction of lipid oxidation products (α,β-unsaturated aldehydes) with lysine residues (Michael addition reactions) and also by interactions with alkoxyl radicals obtained by Fe(II) cleavage of lipid hydroperoxides that are formed. In addition, saturated aldehydes derived from the polyunsaturated fatty acids likely react with lysine residues to form Schiff base adducts.

  2. Novel Bioactivity of Ellagic Acid in Inhibiting Human Platelet Activation

    Directory of Open Access Journals (Sweden)

    Yi Chang


    Full Text Available Pomegranates are widely consumed either as fresh fruit or in beverage form as juice and wine. Ellagic acid possesses potent antioxidative properties; it is known to be an effective phytotherapeutic agent with antimutagenic and anticarcinogenic qualities. Ellagic acid (20 to 80 μM exhibited a potent activity in inhibiting platelet aggregation stimulated by collagen; however, it did not inhibit platelet aggregation stimulated by thrombin, arachidonic acid, or U46619. Treatment with ellagic acid (50 and 80 μM significantly inhibited platelet activation stimulated by collagen; this alteration was accompanied by the inhibition of relative [Ca2+]i mobilization, and the phosphorylation of phospholipase C (PLCγ2, protein kinase C (PKC, mitogen-activated protein kinases (MAPKs, and Akt, as well as hydroxyl radical (OH● formation. In addition, ellagic acid also inhibited p38 MAPK and Akt phosphorylation stimulated by hydrogen peroxide. By contrast, ellagic acid did not significantly affect PKC activation and platelet aggregation stimulated by PDBu. This study is the first to show that, in addition to being considered a possible agent for preventing tumor growth, ellagic acid possesses potent antiplatelet properties. It appears to initially inhibit the PLCγ2-PKC cascade and/or hydroxyl radical formation, followed by decreased phosphorylation of MAPKs and Akt, ultimately inhibiting platelet aggregation.

  3. The effect of linoleic acid on the whole body synthesis rates of polyunsaturated fatty acids from α-linolenic acid and linoleic acid in free-living rats. (United States)

    Domenichiello, Anthony F; Kitson, Alex P; Chen, Chuck T; Trépanier, Marc-Olivier; Stavro, P Mark; Bazinet, Richard P


    Docosahexaenoic acid (DHA) is thought to be important for brain function. The main dietary source of DHA is fish, however, DHA can also be synthesized from precursor omega-3 polyunsaturated fatty acids (n-3 PUFA), the most abundantly consumed being α-linolenic acid (ALA). The enzymes required to synthesize DHA from ALA are also used to synthesize longer chain omega-6 (n-6) PUFA from linoleic acid (LNA). The large increase in LNA consumption that has occurred over the last century has led to concern that LNA and other n-6 PUFA outcompete n-3 PUFA for enzymes involved in DHA synthesis, and therefore, decrease overall DHA synthesis. To assess this, rats were fed diets containing LNA at 53 (high LNA diet), 11 (medium LNA diet) or 1.5% (low LNA diet) of the fatty acids with ALA being constant across all diets (approximately 4% of the fatty acids). Rats were maintained on these diets from weaning for 8 weeks, at which point they were subjected to a steady-state infusion of labeled ALA and LNA to measure DHA and arachidonic acid (ARA) synthesis rates. DHA and ARA synthesis rates were generally highest in rats fed the medium and high LNA diets, while the plasma half-life of DHA was longer in rats fed the low LNA diet. Therefore, increasing dietary LNA, in rats, did not impair DHA synthesis; however, low dietary LNA led to a decrease in DHA synthesis with tissue concentrations of DHA possibly being maintained by a longer DHA half-life.

  4. A New Kind of Ingredients- Arachidonie Acid%新型高级营养强化剂花生四烯酸

    Institute of Scientific and Technical Information of China (English)



    AA(arachidonic acid)is one of the most important PUFAs (polyunsaturated fatty acids) in human body. Studies prove that AA plays an important role in improving life quality especially the intelligent of human race. However, among all the PUFAs AA is the latest one putting into the practical application, mainly because erenow AA has failed to realize its industrialized production.In June 1998 Alking completed eight-years laboratorial study through selecting and breeding AA high-yield bacterium by means of ion cluster bioengineering technology.

  5. [The profile of plasma non-esterified fatty acids in children with different terms of type 1 diabetes mellitus]. (United States)

    Akmurzina, V A; Petryairina, E E; Saveliev, S V; Selishcheva, A A


    Composition and quantitative content of non-esterified fatty acids (NEFA) were investigated in plasma samples of healthy children (12) and children with type 1 diabetes mellitus (DM1) (31) by gas chromatography (GC) after preliminary NEFA solid-phase extraction from plasma lipids. There was a significant (p1) 1.6-fold increase in the total level of NEFA regardless of the disease duration. In the group of DM1 children with the disease period less than 1 year there was an increase in the arachidonic acid (20:4) content (30%) and the oleic acid trans-isomer (18:1) content (82%), and also a decrease in the docosahexaenoic acid (22:6 n3) content (26% ) and the docosapentaenoic acids (22:5 n-6) content (60%). In the group of DM1 children with prolonged course of this disease the altered NEFA levels returned to the normal level.

  6. Breast milk: Fatty acid composition and maternal diet

    Directory of Open Access Journals (Sweden)

    Mihela Dujmović


    Full Text Available Breast milk from healthy and well-nourished mothers is the preferred form of infants´ feeding in the first six months after parturition, and breastfeeding in this period supports the normal growth and development of new-born infants. During the first month postpartum, breast milk changes through three stages: colostrum, transitional milk and mature milk. Mature milk, which is excreted after the 16th day postpartum, contains on average 3.4-4.5 % lipids. Breast milk lipids fulfill 40-55 % of an infant´s daily energy needs and provide a supply of fat-soluble vitamins and fatty acids. The characteristics of milk lipids are largely determined by their fatty acid composition. In this work the general characteristics of breast milk and milk lipids, as well as the influence of maternal diet on composition of fatty acids in breast milk, are discussed. Breast milk provides all dietary essential fatty acids, linoleic acid (C18:2n-6 and α-linolenic acid (C18:3n-3, as well as their longer-chain more-unsaturated metabolites, including arachidonic acid (C20:4n-6 and docosahexaenoic acid (C22:6n-3. Long-chain polyunsaturated fatty acids are of particular importance in visual and neural development, and their content in milk is a reflection of the mother´s current and long-term dietary intake. A positive association has been established between the maternal intake of fish and seafood and the content of polyunsaturated fatty acids (especially docosahexaenoic acid in milk. Numerous researches have been shown that supplementation with docosahexaenoic acids during the last trimester of pregnancy and during lactation significantly increases the content of polyunsaturated fatty acids in breast milk.

  7. Egg fatty acid composition from lake trout fed two Lake Michigan prey fish species. (United States)

    Honeyfield, D.C.; Fitzsimons, J.D.; Tillitt, D.E.; Brown, S.B.


    We previously demonstrated that there were significant differences in the egg thiamine content in lake trout Salvelinus namaycush fed two Lake Michigan prey fish (alewife Alosa pseudoharengus and bloater Coregonus hoyi). Lake trout fed alewives produced eggs low in thiamine, but it was unknown whether the consumption of alewives affected other nutritionally important components. In this study we investigated the fatty acid composition of lake trout eggs when females were fed diets that resulted in different egg thiamine concentrations. For 2 years, adult lake trout were fed diets consisting of four combinations of captured alewives and bloaters (100% alewives; 65% alewives, 35% bloaters; 35% alewives, 65% bloaters; and 100% bloaters). The alewife fatty acid profile had higher concentrations of arachidonic acid and total omega-6 fatty acids than the bloater profile. The concentrations of four fatty acids (cis-13, 16-docosadienoic, eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids) were higher in bloaters than in alewives. Although six fatty acid components were higher in lake trout eggs in 2001 than in 2000 and eight fatty acids were lower, diet had no effect on any fatty acid concentration measured in lake trout eggs in this study. Based on these results, it appears that egg fatty acid concentrations differ between years but that the egg fatty acid profile does not reflect the alewife-bloater mix in the diet of adults. The essential fatty acid content of lake trout eggs from females fed alewives and bloaters appears to be physiologically regulated and adequate to meet the requirements of developing embryos.

  8. Egg fatty acid composition from lake trout fed two Lake Michigan prey fish species. (United States)

    Honeyfield, Dale C; Fitzsimons, John D; Tillitt, Donald E; Brown, Scott B


    We previously demonstrated that there were significant differences in the egg thiamine content in lake trout Salvelinus namaycush fed two Lake Michigan prey fish (alewife Alosa pseudoharengus and bloater Coregonus hoyi). Lake trout fed alewives produced eggs low in thiamine, but it was unknown whether the consumption of alewives affected other nutritionally important components. In this study we investigated the fatty acid composition of lake trout eggs when females were fed diets that resulted in different egg thiamine concentrations. For 2 years, adult lake trout were fed diets consisting of four combinations of captured alewives and bloaters (100% alewives; 65% alewives, 35% bloaters; 35% alewives, 65% bloaters; and 100% bloaters). The alewife fatty acid profile had higher concentrations of arachidonic acid and total omega-6 fatty acids than the bloater profile. The concentrations of four fatty acids (cis-13, 16-docosadienoic, eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids) were higher in bloaters than in alewives. Although six fatty acid components were higher in lake trout eggs in 2001 than in 2000 and eight fatty acids were lower, diet had no effect on any fatty acid concentration measured in lake trout eggs in this study. Based on these results, it appears that egg fatty acid concentrations differ between years but that the egg fatty acid profile does not reflect the alewife-bloater mix in the diet of adults. The essential fatty acid content of lake trout eggs from females fed alewives and bloaters appears to be physiologically regulated and adequate to meet the requirements of developing embryos.

  9. Metabolic engineering for the production of polyunsaturated fatty acids by oleaginous fungus Mortierella alpina 1S-4. (United States)

    Sakuradani, Eiji; Ando, Akinori; Shimizu, Sakayu; Ogawa, Jun


    Researches related with the application of functional lipids such as polyunsaturated fatty acids (PUFAs) have been conducted in various fields with a view to health and dietary requirements. Novel rich sources other than known natural sources such as plant seeds and fish oils are required for increasing demands of PUFAs. The filamentous fungus Mortierella alpina 1S-4 produces triacylglycerols rich in arachidonic acid, i.e., ones reaching 20 g/l in concentration and containing 30-70% arachidonic acid as total fatty acids. Various mutants derived from M. alpina 1S-4 have led to the production of oils containing various PUFAs. Molecular breeding of M. alpina strains by means of manipulation of the genes involved in PUFA biosynthesis facilitates improvement of PUFA productivity and elucidation of the functions of their enzymes. This review describes practical PUFA production through mutant breeding, functional analyses of the genes of the enzymes involved in PUFA biosynthesis, and recent advances in unique PUFA production through molecular breeding.

  10. High Fat Diet Exposure during Fetal Life Enhances Plasma and Hepatic Omega-6 Fatty Acid Profiles in Fetal Wistar Rats

    Directory of Open Access Journals (Sweden)

    Marlon E. Cerf


    Full Text Available Pregnant rats were fed a high fat diet (HFD for the first (HF1, second (HF2, third (HF3 or all three weeks (HFG of gestation. Maintenance on a HFD during specific periods of gestation was hypothesized to alter fetal glycemia, insulinemia, induce insulin resistance; and alter fetal plasma and hepatic fatty acid (FA profiles. At day 20 of gestation, fetal plasma and hepatic FA profiles were determined by gas chromatography; body weight, fasting glycemia, insulinemia and the Homeostasis Model Assessment (HOMA-insulin resistance were also determined. HF3 fetuses were heaviest concomitant with elevated glycemia and insulin resistance (p < 0.05. HFG fetuses had elevated plasma linoleic (18:2 n-6 and arachidonic (20:4 n-6 acid proportions (p < 0.05. In the liver, HF3 fetuses displayed elevated linoleic, eicosatrienoic (20:3 n-6 and arachidonic acid proportions (p < 0.05. HFG fetuses had reduced hepatic docosatrienoic acid (22:5 n-3 proportions (p < 0.05. High fat maintenance during the final week of fetal life enhances hepatic omega-6 FA profiles in fetuses concomitant with hyperglycemia and insulin resistance thereby presenting a metabolically compromised phenotype.

  11. Long-chain polyunsaturated fatty acids (LCPUFA) from genesis to senescence: the influence of LCPUFA on neural development, aging, and neurodegeneration. (United States)

    Janssen, Carola I F; Kiliaan, Amanda J


    Many clinical and animal studies demonstrate the importance of long-chain polyunsaturated fatty acids (LCPUFA) in neural development and neurodegeneration. This review will focus on involvement of LCPUFA from genesis to senescence. The LCPUFA docosahexaenoic acid and arachidonic acid are important components of neuronal membranes, while eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid also affect cardiovascular health and inflammation. In neural development, LCPUFA deficiency can lead to severe disorders like schizophrenia and attention deficit hyperactivity disorder. Perinatal LCPUFA supplementation demonstrated beneficial effects in neural development in humans and rodents resulting in improved cognition and sensorimotor integration. In normal aging, the effect of LCPUFA on prevention of cognitive impairment will be discussed. LCPUFA are important for neuronal membrane integrity and function, and also contribute in prevention of brain hypoperfusion. Cerebral perfusion can be compromised as result of obesity, cerebrovascular disease, hypertension, or diabetes mellitus type 2. Last, we will focus on the role of LCPUFA in most common neurodegenerative diseases like Alzheimer's disease and Parkinson's disease. These disorders are characterized by impaired cognition and connectivity and both clinical and animal supplementation studies have shown the potential of LCPUFA to decrease neurodegeneration and inflammation. This review shows that LCPUFA are essential throughout life.

  12. Effect of Acetic Acid and Low Molecular Weight Component of Mature Vinegar on Platelet Aggregation%醋酸及陈醋低分子量成分的抗血小板聚集活性

    Institute of Scientific and Technical Information of China (English)

    何璐薇; 李志敏; 孙严; 张艳艳; 范俊峰


    The effects of acetic acid and low molecular weight component of mature vinegar on platelet aggregation induced by arachidonic acid and collagen were assayed. Results showed that the maximal inhibition rate of acetic acid on platelet aggregation induced by collagen was 75. 95% and the minimum concentration of acetic acid which could inhibit the aggregation rate was 0. 05mol/L while the maximal inhibition rate of acetic acid on platelet aggregation induced by arachidonic acid was 83.62% and the minimum concentration acetic acid was 0. 01 mol/L Compared with the control group, acetic acid and low molecular weight component of mature vinegar independently inhibited the platelet aggregation induced by arachidonic acid and collagen obviously, and the effect of acetic acid on platelet aggregation induced by arachidonic acid was greater than collagen.%以食醋中的醋酸和陈醋低分子成分为研究对象,评价其对由花生四烯酸和胶原诱导的血小板聚集反应的影响。结果表明,醋酸对由胶原诱导的血小板聚集的最大抑制率为75.95%,能起到作用的最低醋酸浓度为0.05mol/L;醋酸对由花生四烯酸诱导的血小板聚集的最大抑制率为83.62%,能起到作用的最低醋酸浓度为0.01mol/L。与空白对照组相比,醋酸及陈醋低分子成分均对由花生四烯酸和胶原诱导的血小板聚集有明显抑制作用,且抑制作用均呈浓度依赖型,其中醋酸对以花生四烯酸为诱导剂引起的血小板聚集的作用更为明显。

  13. Fatty acid composition, eicosanoid production and permeability in skin tissues of rainbow trout (Oncorhynchus mykiss) fed a control or an essential fatty acid deficient diet. (United States)

    Ghioni, C; Bell, J G; Bell, M V; Sargent, J R


    Rainbow trout (Oncorhynchus mykiss) were fed either a control diet containing fish oil or an essential fatty acid (EFA) deficient diet containing only hydrogenated coconut oil and palmitic acid as lipid source (93.4% saturated fatty acids) for 14 weeks and the fatty acid compositions of individual phospholipid classes from skin and opercular membrane (OM) determined. The permeability of skin and OM to water and the production of eicosanoids in skin and gills challenged with the Ca2+ ionophore A23187 were also measured. Phospholipid (PL) fatty acid compositions were substantially modified in EFA-deficient fish, with increased saturated fatty acids and decreased polyunsaturated fatty acids (PUFA), especially arachidonic acid (AA) and eicosapentaenoic acid (EPA), while docosahexaenoic acid (DHA) was largely retained. The onset of EFA deficiency was shown by the appearance of n-9 PUFA, particularly 20:3n-9. The main effects of EFA deficiency on phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were to increase saturated fatty acids and monoenes, especially 16:1 and 18:1, and to decrease EPA and DHA. The content of DHA in phosphatidylserine (PS) was high in control animals (40% in skin and 35% in opercular membrane) and was mostly retained in EFA deficient animals. Arachidonic acid (AA) was the most abundant PUFA esterified to phosphatidylinositol (PI) and was significantly reduced in EFA deficient animals (from 31% to 13% in skin), where a large amount of 20:3n-9 (9% in skin) was also present. Influxes and effluxes of water through skin and opercular membrane were measured in vitro. No differences were detected between rainbow trout fed the control or the EFA deficient diet. 12-Hydroxyeicosatetraenoic acid (12-HETE), 12-hydroxyeicosapentaenoic acid (12-HEPE) and 14-hydroxydocosahexaenoic acid (14-HDHE) could not be detected in skin from control or EFA deficient fish. There was no difference between control and EFA deficient trout in the levels of leukotriene C

  14. Report on the distribution of essential and non essential fatty acids in common edible fishes of Porto-Novo coastal waters, southeast coast of India

    Institute of Scientific and Technical Information of China (English)



    Objective: The objective of the study was to evaluate the essential and non essential fatty acids and the distribution of Omega-3 and Omega-6 fatty acids in twenty commonly consumed edible fishes of parangipettai coastal waters. Methods: For fatty acid analysis, each fish specimens were beheaded, eviscerated and filleted manually. The tissue samples were oven dried at 67℃ for 24hrs.After that the samples ware grounded finely with pestle and mortar. The saponified samples were cooled at room temperature for 25 min, they were acidified and methylated by adding 2 ml 54% 6 N Hcl in 46% aqueous methanol and incubated at 80℃ for 10 min in water bath. Following the base wash step, the FAMEs were cleaned in anhydrous sodium sulphate and then transferred in to GC sample vial for analysis. FAMEs were separated by gas chromatograph. Results: The results of the present study revealed that the most abundant individual FAs were Palmitic acid, Oleic acid, Arachidonic acid (AA), Docosahexaenoic acid (DHA) in most the tissues. The total Arachidonic acid (C20:4ω-6) was found to be higher proportion (0.17-4.86%), when compared with other Omega-6 fatty acids. The values found for Linoleic acid (C18:2 ω-6) ranging from 0-7.23%. Siganus javus has 7.23% of Linoleic acid. Conclusion: Fatty acids are the principle components in lipids. The nutritional importance of fish consumption is in great extent associated with the content of omega-3 fatty acids. Sea food is an important dietary food for human beings. It constitute higher amount of protein, lipids, vitamins and essential and nonessential metals and low concentration of carbohydrates.

  15. Serum fatty acid in patients with acute myocardial infarction in Gorgan

    Directory of Open Access Journals (Sweden)

    Abdoljalal Marjani


    Full Text Available Introduction: The present study aimed to assess serum fatty acid in patients with acute myocardial infarction in Gorgan, Iran. Material and Methods: The study conducted on the thirty and five subjects with acute myocardial infarction who were referred to the intensive Coronary Care Unit in 5th Azar in Gorgan. Results: The content of palmitoleic acid (16:1 was significantly higher in serum fatty acid of the patients than of the control groups (P=0.019, whereas oleic acid (18:1, linoleic acid (18:2, _-linolenic acid (18:3, arachidonic acid (20:4 and Eicosapentaenoic acid (EPA were significantly higher in the control groups than the patients (P<0.0001, P=0.013, P=0.042, P=0,001 and P=0.022 respectively. Conclusion: This study showed that the content of polyunsaturated fatty acids in serum fatty acid component was decreased in acute myocardial infarction patients. These results suggest that there may be some protective effects of poly unsaturated fatty acid against myocardial infarction.

  16. Effet des acides gras sur l’inflammation et le cancer

    Directory of Open Access Journals (Sweden)

    Blouin Jean-Marc


    Full Text Available A substantial body of evidence supports the conclusion that chronic inflammation is a causative factor in a variety of cancers. Inflammatory mediators include metabolites of arachidonic acid, cytokines, chemokines, and free radicals. These mediators increase cell proliferation, mutagenesis, oncogene activation, with ultimately the loss of cell growth control. Among the nutritional factors that can influence inflammation and cancerogenesis, fatty acids are clearly the most directly involved. Indeed, omega-3 and omega-6 polyunsaturated fatty acids exert opposite effects on inflammation and potentially on tumor formation. The present review analyses in a non-exhaustive manner some of the mechanisms that have been proposed to explain how omega-6 can be detrimental while omega-3 have beneficial effects.

  17. N-3 polyunsaturated fatty acids do not affect the cytokine response to strenuous exercise

    DEFF Research Database (Denmark)

    Toft, A.D.; Thorn, Mette; Ostrowski, Kenneth


    (PUFA), for 6 wk or to receive no supplementation (n = 10) before participating in The Copenhagen Marathon 1998. Blood samples were collected before the race, immediately after, and 1.5 and 3 h postexercise. The fatty acid composition in blood mononuclear cells (BMNC) differed between the fish oil......The aim of the present study was to investigate whether fish oil supplementation was able to modulate the acute-phase response to strenuous exercise. Twenty male runners were randomized to receive supplementation (n = 10) with 6.0 g fish oil daily, containing 3.6 g n-3 polyunsaturated fatty acids......-supplemented and the control group, showing incorporation of n-3 PUFA and less arachidonic acid in BMNC in the supplemented group. The plasma levels of tumor necrosis factor-alpha, interleukin-6, and transforming growth factor-beta(1) peaked immediately after the run, the increase being 3-, 92-, and 1.1-fold, respectively...

  18. Evaluation of docosahexaenoic acid in a dog model of hypertension induced left ventricular hypertrophy. (United States)

    Stanley, William C; Cox, James W; Asemu, Girma; O'Connell, Kelly A; Dabkowski, Erinne R; Xu, Wenhong; Ribeiro, Rogerio F; Shekar, Kadambari C; Hoag, Stephen W; Rastogi, Sharad; Sabbah, Hani N; Daneault, Caroline; des Rosiers, Christine


    Marine n-3 polyunsaturated fatty acids alter cardiac phospholipids and prevent cardiac pathology in rodents subjected to pressure overload. This approach has not been evaluated in humans or large animals with hypertension-induced pathological hypertrophy. We evaluated docosahexaenoic acid (DHA) in old female dogs with hypertension caused by 16 weeks of aldosterone infusion. Aldosterone-induced hypertension resulted in concentric left ventricular (LV) hypertrophy and impaired diastolic function in placebo-treated dogs. DHA supplementation increased DHA and depleted arachidonic acid in cardiac phospholipids, but did not improve LV parameters compared to placebo. Surprisingly, DHA significantly increased serum aldosterone concentration and blood pressure compared to placebo. Cardiac mitochondrial yield was decreased in placebo-treated hypertensive dogs compared to normal animals, which was prevented by DHA. Extensive analysis of mitochondrial function found no differences between DHA and placebo groups. In conclusion, DHA did not favorably impact mitochondrial or LV function in aldosterone hypertensive dogs.

  19. Prostaglandin H synthase-mediated bioactivation of the amino acid pyrolysate product Trp P-2

    Energy Technology Data Exchange (ETDEWEB)

    Petry, T.W.; Krauss, R.S.; Eling, T.E.


    We report evidence that the mutagen and carcinogen 3-amino-1-methyl-5H pyrido(4,3b)indole (Trp P-2) is a substrate for co-oxidation by prostaglandin H synthase (PHS) in ram seminal vesicle (RSV) microsomes. Trp P-2 serves as a reducing cofactor for the hydroperoxidase activity of PHS as shown by the concentration-dependent inhibition of the hydroperoxidase catalyzed incorporation of molecular oxygen into phenylbutazone. Spectral data suggest that this metabolism results in disruption of the double bond conjugation within the nucleus of the molecule. A single metabolite peak which was dependent upon arachidonic acid and substrate concentration was separated from the parent compound by h.p.l.c. following incubation with RSV microsomes. Co-oxidation of Trp P-2 produced reactive intermediates which bound covalently to microsomal protein (9 nmol/mg) and to calf thymus DNA (475 pmol/mg). Binding was inhibited by indomethacin, and supported by substitution of hydrogen peroxide for arachidonic acid. These data suggest a possible role for PHS in the in situ activation of Trp P-2 to its ultimate carcinogenic form in tissues which contain PHS.

  20. Final report of the amended safety assessment of Glyceryl Laurate, Glyceryl Laurate SE, Glyceryl Laurate/Oleate, Glyceryl Adipate, Glyceryl Alginate, Glyceryl Arachidate, Glyceryl Arachidonate, Glyceryl Behenate, Glyceryl Caprate, Glyceryl Caprylate, Glyceryl Caprylate/Caprate, Glyceryl Citrate/Lactate/Linoleate/Oleate, Glyceryl Cocoate, Glyceryl Collagenate, Glyceryl Erucate, Glyceryl Hydrogenated Rosinate, Glyceryl Hydrogenated Soyate, Glyceryl Hydroxystearate, Glyceryl Isopalmitate, Glyceryl Isostearate, Glyceryl Isostearate/Myristate, Glyceryl Isostearates, Glyceryl Lanolate, Glyceryl Linoleate, Glyceryl Linolenate, Glyceryl Montanate, Glyceryl Myristate, Glyceryl Isotridecanoate/Stearate/Adipate, Glyceryl Oleate SE, Glyceryl Oleate/Elaidate, Glyceryl Palmitate, Glyceryl Palmitate/Stearate, Glyceryl Palmitoleate, Glyceryl Pentadecanoate, Glyceryl Polyacrylate, Glyceryl Rosinate, Glyceryl Sesquioleate, Glyceryl/Sorbitol Oleate/Hydroxystearate, Glyceryl Stearate/Acetate, Glyceryl Stearate/Maleate, Glyceryl Tallowate, Glyceryl Thiopropionate, and Glyceryl Undecylenate. (United States)


    The safety of 43 glyceryl monoesters listed as cosmetic ingredients was reviewed in a safety assessment completed in 2000. Additional safety test data pertaining to Glyceryl Rosinate and Glyceryl Hydrogenated Rosinate were received and served as the basis for this amended report. Glyceryl monoesters are used mostly as skin-conditioning agents--emollients and/or surfactant--emulsifying agents in cosmetics. The following 20 glyceryl monoesters are currently reported to be used in cosmetics: Glyceryl Laurate, Glyceryl Alginate, Glyceryl Arachidonate, Glyceryl Behenate, Glyceryl Caprylate, Glyceryl Caprylate/Caprate, Glyceryl Cocoate, Glyceryl Erucate, Glyceryl Hydroxystearate, Glyceryl Isostearate, Glyceryl Lanolate, Glyceryl Linoleate, Glyceryl Linolenate, Glyceryl Myristate, Glyceryl Oleate/Elaidate, Glyceryl Palmitate, Glyceryl Polyacrylate, Glyceryl Rosinate, Glyceryl Stearate/Acetate, and Glyceryl Undecylenate. Concentration of use data received from the cosmetics industry in 1999 indicate that Glyceryl Monoesters are used at concentrations up to 12% in cosmetic products. Glyceryl Monoesters are not pure monoesters, but are mostly mixtures with mono-, di-, and tri-esters. The purity of commercial and conventional Monoglyceride (Glyceryl Monoester) is a minimum of 90%. Glyceryl Monoesters (monoglycerides) are metabolized to free fatty acids and glycerol, both of which are available for the resynthesis of triglycerides. Glyceryl Laurate enhanced the penetration of drugs through cadaverous skin and hairless rat skin in vitro and has been described as having a wide spectrum of antimicrobial activity. A low-grade irritant response was observed following inhalation of an aerosol containing 10% Glyceryl Laurate by test animals. Glyceryl monoesters have little acute or short-term toxicity in animals, and no toxicity was noted following chronic administration of a mixture consisting mostly of glyceryl di- and mono- esters. Glyceryl Laurate did have strong hemolytic

  1. 脂肪酸分析方法研究进展%Progress in analysis methods of fatty acids

    Institute of Scientific and Technical Information of China (English)

    高瑞萍; 彭见林; 刘辉; 赵国华


    A number of chronic diseases such as obesity,diabetes,cardiovascular disease are caused by taking overdose fatty acids.However,the moderate amount of unsaturayed fatty acids such as α-linolenic acids(ALA),arachidonic acid(AA)and eicosapentaenoic acid(EPA),which not only be beneficial to human health,but also can improve body functions.Analysis methods of fatty acids are quite mature abroad.Analysis methods of fatty acids were reviewed to introduce the extraction and determination methods.The purpose was to provide necessary references to speed the study process of fatty acids of our country.%脂肪酸的过量摄入会引发一些慢性疾病,如肥胖、糖尿病、心血管疾病等,严重危害人体健康。而适量不饱和脂肪酸的摄入,包括α-亚麻酸(α-linolenic acids,ALA)、花生四烯酸(arachidonic acid,AA)、二十碳二烯酸(eicosapentaenoic acid,EPA)等不仅有益于身体健康,还能改善机体功能。国外对脂肪酸的分析已相当成熟,应用了许多现代分析技术。鉴于脂肪酸在食品领域的重要性,重点对国外脂肪酸(fatty acids,FAs)的分析方法进行综述,包括萃取和分析等方面的内

  2. Synthesis of docosahexaenoic acid from eicosapentaenoic acid in retina neurons protects photoreceptors from oxidative stress. (United States)

    Simón, María Victoria; Agnolazza, Daniela L; German, Olga Lorena; Garelli, Andrés; Politi, Luis E; Agbaga, Martin-Paul; Anderson, Robert E; Rotstein, Nora P


    Oxidative stress is involved in activating photoreceptor death in several retinal degenerations. Docosahexaenoic acid (DHA), the major polyunsaturated fatty acid in the retina, protects cultured retina photoreceptors from apoptosis induced by oxidative stress and promotes photoreceptor differentiation. Here, we investigated whether eicosapentaenoic acid (EPA), a metabolic precursor to DHA, had similar effects and whether retinal neurons could metabolize EPA to DHA. Adding EPA to rat retina neuronal cultures increased opsin expression and protected photoreceptors from apoptosis induced by the oxidants paraquat and hydrogen peroxide (H2 O2 ). Palmitic, oleic, and arachidonic acids had no protective effect, showing the specificity for DHA. We found that EPA supplementation significantly increased DHA percentage in retinal neurons, but not EPA percentage. Photoreceptors and glial cells expressed Δ6 desaturase (FADS2), which introduces the last double bond in DHA biosynthetic pathway. Pre-treatment of neuronal cultures with CP-24879 hydrochloride, a Δ5/Δ6 desaturase inhibitor, prevented EPA-induced increase in DHA percentage and completely blocked EPA protection and its effect on photoreceptor differentiation. These results suggest that EPA promoted photoreceptor differentiation and rescued photoreceptors from oxidative stress-induced apoptosis through its elongation and desaturation to DHA. Our data show, for the first time, that isolated retinal neurons can synthesize DHA in culture. Docosahexaenoic acid (DHA), the major polyunsaturated fatty acid in retina photoreceptors, and its precursor, eicosapentaenoic acid (EPA) have multiple beneficial effects. Here, we show that retina neurons in vitro express the desaturase FADS2 and can synthesize DHA from EPA. Moreover, addition of EPA to these cultures protects photoreceptors from oxidative stress and promotes their differentiation through its metabolization to DHA.

  3. Assesment of polyunsaturated fatty acids in cord blood of infants of diabetic mothers

    Institute of Scientific and Technical Information of China (English)

    Galila M Mokhar; Soha M Abd EI Dayem; Nermine H Sayed; Sohair abd El Maksod; Manal El Shamaa; Hani M El Mikaty


    Objective:To assess whether infants of diabetic mothers [pre pregnancy diabetics (PPD) and gestational diabetics mellitus (GDM)] have compromised arachidonic and docosahexaenoic acids in their plasma and the relationship with deficiency of the same compounds in their mothers. Methods:This study was conducted on 30 diabetic mothers (both PPD and GDM) and their infants. Twenty healthy infants and their mothers with age and sex matched were included as controls. All infant (of diabetic and non diabetic mothers) were subjected to assessment of APGAR Scoring, thorough history taking and anthropometric measures. Lipid profile components as well as polyunsaturated fatty acids(PUFA) were assessed in diabetic GDM and PPD and non diabetic mothers as well as in their babies. Results: High-density lipoproteir(HDL) level was found to be significantly lower in diabetic mothers (specially those with PPD) compared to non diabetic ones, whereas no significant difference was found between babies of the two groups. Also, the current study revealed that diabet-ic mothers (GDM and PPD) and their babies had significantly higher levels of PUFA precursors linoleic acids (LA) and alpha linoleic acids (ALA). PUFA arachidonic acid (AA) and docosahexaenoic acids (DHA) were found to be significantly lower in diabetic mothers (GDM and PPD) compared to non diabetic mothers, and same results were found in the babies of the two groups. Conclusion: Neonates with diabetic mothers (both GDM and PPD) have highly compromised plasma levels of AA and DHA PUFA, which affects the child well being by far, and produces hazardous multi-system complications on the long run.

  4. Essential fatty acids influence metabolic rate and tolerance of hypoxia in Dover sole ( Solea solea ) larvae and juveniles

    DEFF Research Database (Denmark)

    McKenzie, David; Lund, Ivar; Pedersen, Per Bovbjerg


    Dover sole (Solea solea, Linneaus 1758) were raised from first feeding on brine shrimp (Artemia sp.) with different contents and compositions of the essential fatty acids (EFA) arachidonic acid (ARA, 20:4n - 6); eicosapentaenoic acid (EPA, 20:5n - 3), and docosahexaenoic acid (DHA, 22:6n - 3......), and their metabolic rate and tolerance to hypoxia measured prior to and following metamorphosis and settlement. Four dietary Artemia preparations were compared: (1) un-enriched; (2) enriched with a commercial EFA mixture (Easy DHA SELCO Emulsion); (3) enriched with a marine fish oil combination (VEVODAR and Incromega......-crit, but juveniles fed on un-enriched Artemia still exhibited higher P-crit and agitation thresholds than the other groups. Sole fed un-enriched Artemia had significantly lower contents of EFA in their tissues, both before and after settlement. Thus, enriching live feeds with EFA has significant effects...


    Directory of Open Access Journals (Sweden)

    N. N. Kushnarenko


    Full Text Available Aim. To study blood levels of non-esterified fatty acids (NEFAs and adenyl nucleotides, and fatty acids levels in lipids of erythrocyte membranes in patients with primary gout associated with arterial hypertension (HT. Material and methods. 175 male patients with primary gout were included in the study. According to 24-hour blood pressure (BP monitoring results patients were split into two groups: 74 patients with normal BP (group 1 and 101 patients with HT (group 2. 29 healthy age-comparable subjects were included into control group. Uric acid, total NEFAs and glycerol blood levels were studied in all patients. Adenyl nucleotides (ATP , ADP and AMP levels were determined in erythrocytes. Higher fatty acid levels were specified in lipids of erythrocyte membranes, including the following acids: myristinic (С14:0, palmitinic (С16:0, stearic (С18:0, pentadecanic (С15:0, heptadecanic (С17:0, pentadecenic (С15:1, heptadecenic (С17:1, palmitooleic (С16:1, oleic (С18:1, linoleic (С18:2ω6, α-linolenic (С18:3ω3, γ-linolenic (С18:3ω6, dihomo-γ-linolenic (С20:3ω6, arachidonic (С20:4ω6, eicosapentaenoic (С20:5ω3, and docosapentaenoic (С22:5ω3. Results and discussion. Hypertensive patients with gout demonstrated higher NEFAs blood level and greater changes in ATP-ADP-AMP system than normotensive gout patients and healthy subjects as well as 2.2 and 3.7 times higher NEFAs/ATP ratio, respectively. In hypertensive patients with primary gout the composition of fatty acids in erythrocyte membranes lipids changed due to increase in saturated fatty acids amount and decrease in unsaturated fatty acids amount, at that monoenic acid levels increased while polyenic acid levels decreased in unsaturated acids composition. Hypertensive patients with gout shown 1.3 and 2.5 times less levels of ω-3 poly-unsaturated fatty acids (PUFA than normotensive gout patients and healthy subjects, respectively. At the same time ω-6 PUFA levels changed in

  6. Comparison of seizure reduction and serum fatty acid levels after receiving the ketogenic and modified Atkins diet. (United States)

    Porta, Natacha; Vallée, Louis; Boutry, Elisabeth; Fontaine, Monique; Dessein, Anne-Frédérique; Joriot, Sylvie; Cuisset, Jean-Marie; Cuvellier, Jean-Christophe; Auvin, Stéphane


    The ketogenic diet (KD) and the modified Atkins diet are effective therapies for intractable epilepsy. We compared retrospectively the KD and modified Atkins diet in 27 children and also assessed serum long chain fatty acid profiles. After 3 months, using an intent-to-treat analysis, the KD was more successful, with >50% seizure reduction in 11/17 (65%) vs. 2/10 (20%) with the modified Atkins diet, p=0.03. After 6 months, however, the difference was no longer significant: 7/17 (41%) vs. 2/10 (20%) (p=0.24). We observed a preventive effect of both diets on the occurrence of status epilepticus. After 1 and 3 months of either diet, responders experienced a significant decrease in serum arachidonic acid concentration compared to non-responders. The KD and modified Atkins diet led to seizure reduction in this small pilot series, with slightly better results after 3 months with the KD, but not after 6 months. The decrease of serum arachidonic acid levels might be involved in the anticonvulsive effects of KD or modified Atkins diet.

  7. Comparative Serum Fatty Acid Profiles of Captive and Free-Ranging Cheetahs (Acinonyx jubatus) in Namibia. (United States)

    Tordiffe, Adrian S W; Wachter, Bettina; Heinrich, Sonja K; Reyers, Fred; Mienie, Lodewyk J


    Cheetahs (Acinonyx jubatus) are highly specialised large felids, currently listed as vulnerable on the IUCN red data list. In captivity, they are known to suffer from a range of chronic non-infectious diseases. Although low heterozygosity and the stress of captivity have been suggested as possible causal factors, recent studies have started to focus on the contribution of potential dietary factors in the pathogenesis of these diseases. Fatty acids are an important component of the diet, not only providing a source of metabolisable energy, but serving other important functions in hormone production, cellular signalling as well as providing structural components in biological membranes. To develop a better understanding of lipid metabolism in cheetahs, we compared the total serum fatty acid profiles of 35 captive cheetahs to those of 43 free-ranging individuals in Namibia using gas chromatography-mass spectrometry. The unsaturated fatty acid concentrations differed most remarkably between the groups, with all of the polyunsaturated and monounsaturated fatty acids, except arachidonic acid and hypogeic acid, detected at significantly lower concentrations in the serum of the free-ranging animals. The influence of age and sex on the individual fatty acid concentrations was less notable. This study represents the first evaluation of the serum fatty acids of free-ranging cheetahs, providing critical information on the normal fatty acid profiles of free-living, healthy individuals of this species. The results raise several important questions about the potential impact of dietary fatty acid composition on the health of cheetahs in captivity.

  8. Fatty acid compositions of seed oils of Haematostaphis barteri and Ximenia americana. (United States)

    Eromosele, C O; Eromosele, I C


    The fatty acid compositions of the seed oils of Haematostaphis barteri (blood plum) and Ximenia americana (Wild olive) plants were determined by the Gas Chromatography Mass Spectroscopy (GC-MS) technique. H. barteri contained six fatty acids with oleic (69.35%) and stearic (15.40%) the most abundant unsaturated and saturated fatty acids, respectively. Unsaturated higher fatty acids, namely Eicosadienoic (6.92%) and Erucic acid (2.74%) were detected and the total unsaturation for the oil was 79.01%. For X. americana, 10 fatty acids were identified of which seven were unsaturated yielding a total unsaturation of 92.42%. The oil contained essential fatty acids that is, Linoleic (1.34%), Linolenic (10.31%), Arachidonic (0.60%) and varying levels of unsaturated higher fatty acids, namely, Eicosatrienoic (3.39%), Erucic (3.46%) and Nervonic (1.23%) acids. The level of Oleic acid (72.09%) in the oil was close to the value for H. barteri.

  9. Castration modifies aortic vasoreactivity and serum fatty acids in a sucrose-fed rat model of metabolic syndrome. (United States)

    Perez, Israel; El Hafidi, Mohammed; Carvajal, Karla; Baños, Guadalupe


    Levels of testosterone and estradiol influence the incidence of cardiovascular diseases: generally, estrogens in females are protective before menopause; coronaropathies, hypertension, and dyslipidemias in normal men are more frequent at comparable ages. We investigated the modulation by castration of in vitro vasoreactivity, serum lipid content, and systolic blood pressure (SBP) in rats with sucrose-induced metabolic syndrome. The main characteristics of the rat model are: hypertriglyceridemia, moderately high blood pressure, intra-abdominal accumulation of adipose tissue, hyperinsulinemia, nephropathy, increased oxidative stress, and altered vasoreactivity. Male weanling rats received 30% sucrose solution for 16 weeks (metabolic syndrome; MS), controls (C) had plain water; both had commercial rodent chow. They were subdivided into five groups with two subgroups each: Group 1, intact C and MS rats, Groups 2-5, C and MS rats castrated for periods of 16, 12, 8, and 4 weeks. At the end of the study period, systolic blood pressure was measured, and blood and aortas were obtained for fatty acid determination and vasoreactivity assays, respectively. After 16 weeks' sucrose treatment MS aortas showed hypercontractility and decreased vasodilation. Palmitic and palmitoleic acids were increased in MS versus C. Arachidonic acid levels in MS were lower than in intact or castrated C. Long-term castration of 16 weeks normalized the levels of palmitic and oleic acids. With the shorter periods of castration, contractility increased and relaxation decreased in C and MS, but it was more significant in C. Regarding fatty acid composition, long-term castration increased polyunsaturated (arachidonic and eicosapentaenoic) fatty acids. The shorter periods did not modify the fatty acid profile in either C or MS. Metabolic syndrome altered SBP, aortic reactivity, and levels of fatty acids; castration of long duration normalized them in some cases.

  10. Brain docosahexaenoic acid status and learning in young rats submitted to dietary long-chain polyunsaturated fatty acid deficiency and supplementation limited to lactation. (United States)

    García-Calatayud, Salvador; Redondo, Carlos; Martín, Eva; Ruiz, José Ignacio; García-Fuentes, Miguel; Sanjurjo, Pablo


    N-3 fatty acid deficiency has been related to decreased docosahexaenoic acid (DHA) and increased docosapentaenoic acid (DPA) levels in brain and to learning disadvantages. The influence of n-3 deficiency and supplementation on brain fatty acids and learning were investigated in young rats. Newborn Wistar rats were assigned to three groups of cross-foster mothers. The control group (C) was nursed by mothers that received essential fatty acids during pregnancy and lactation, and the deficient group (D) was nursed by mothers that did not receive those fatty acids. The supplemental group (S) had the same conditions as D, receiving an additional DHA and arachidonic acid supplement during lactation. Cerebral cortex and hippocampus fatty acid composition was examined using thin-layer and capillary column gas chromatography, and learning was measured by passive-avoidance procedure. D brains showed low DHA and high DPA levels, but S brain composition was similar to C. Learning in the S group was unaffected, but in the D group, it was poorer than C. Learning was directly correlated with DHA levels and inversely with DPA levels in brain. Low DHA and high DPA brain levels both were correlated with poor learning. DPA seems not to be a suitable brain functional analogue of DHA, and DHA supplementation reversed both biochemical and learning adverse effects observed in n-3 deficiency.

  11. Hyperoxia Elevates Adrenic Acid Peroxidation in Marine Fish and Is Associated with Reproductive Pheromone Mediators

    Directory of Open Access Journals (Sweden)

    Ming Long Sirius Chung


    Full Text Available The development of oxidative stress in the marine ecosystem is a concurring concern in fish reproductive behavior. Marine fish being rich in polyunsaturated fatty acids (PUFA are precursors of prostaglandin pheromone mediators but also vulnerable to lipid peroxidation. It is yet to be determined if hypoxia or hyperoxia environment, a cumulative effect in the marine ecosystem affect pheromone mediators in fish, and to understand if this is associated with the generation of oxidized lipid products of PUFA. Novel oxidized lipid metabolites, isoprostanoids (15-F2t-isoprostane, 7(RS-7-F2t-dihomo-isoprostane, 17(RS-17-F2t-dihomo-isoprostane, 8-F3t-isoprostane, 4(RS-4-F4t-neuroprostane, 10-F4t-neuroprostane, isofuranoids (isofurans, 10-epi-17(RS-SC-Δ15-11-dihomo-isofuran and neurofurans, hydroxyeicosatetraenoic acids and resolvins, PUFA (arachidonic, adrenic, eicosapentaenoic and docosahexaenoic acids and prostaglandin pheromone mediators in fish muscle were determined in marine male and female fish muscles before and after interaction in a hypoxia or hyperoxia environment. Reproductive behaviors were also assessed. Our study showed oxidized lipid metabolites of arachidonic, eicosapentaenoic, and docosahexaenoic acids were not influenced by hypoxia and hyperoxia exposure in the fishes and no gender differences were found. However, adrenic acid and its oxidized products, 17(RS-17-F2t-dihomo-isoprostane and 10-epi-17(RS-SC-Δ15-11-dihomo-isofuran showed strong correspondence with male fish pheromone mediators and reproductive behavior when under oxidative stress especially, hyperoxia. The occurrence of hypoxia and hyperoxia in the marine ecosystem may not be detrimental to marine fish and instead presents as being beneficial in reproductive behavior.

  12. Designer laying hen diets to improve egg fatty acid profile and maintain sensory quality. (United States)

    Goldberg, Erin M; Ryland, Donna; Gibson, Robert A; Aliani, Michel; House, James D


    The fatty acid composition of eggs is highly reflective of the diet of the laying hen; therefore, nutritionally important fatty acids can be increased in eggs in order to benefit human health. To explore the factors affecting the hen's metabolism and deposition of fatty acids of interest, the current research was divided into two studies. In Study 1, the fatty acid profile of eggs from Bovan White hens fed either 8%, 14%, 20%, or 28% of the omega-6 fatty acid, linoleic acid (LA) (expressed as a percentage of total fatty acids), and an additional treatment of 14% LA containing double the amount of saturated fat (SFA) was determined. Omega-6 fatty acids and docosapentaenoic acid (DPA) in the yolk were significantly (P hens fed either (1) 15% or 30% of the omega-3 fatty acid, alpha-linolenic acid (ALA) (of total fatty acids), and (2) low (0.5), medium (1), or high (2) ratios of SFA: LA+OA. Increasing this ratio resulted in marked increases in lauric acid, ALA, EPA, DPA, and docosahexaenoic acid (DHA), with decreases in LA and arachidonic acid. Increasing the dietary ALA content from 15% to 30% (of total fatty acids) did not overcome the DHA plateau observed in the yolk. No significant differences (P ≥ 0.05) in aroma or flavor between cooked eggs from the different dietary treatments were observed among trained panelists (n = 8). The results showed that increasing the ratio of SFA: LA+OA in layer diets has a more favorable effect on the yolk fatty acid profile compared to altering the LA content at the expense of OA, all while maintaining sensory quality.

  13. Health benefits of docosahexaenoic acid (DHA) (United States)

    Horrocks, L A; Yeo, Y K


    meat and eggs, but is not usually present in infant formulas. EPA, another long-chain n-3 fatty acid, is also present in fatty fish. The shorter chain n-3 fatty acid, alpha-linolenic acid, is not converted very well to DHA in man. These longchain n-3 fatty acids (also known as omega-3 fatty acids) are now becoming available in some foods, especially infant formula and eggs in Europe and Japan. Fish oil decreases the proliferation of tumour cells, whereas arachidonic acid, a longchain n-6 fatty acid, increases their proliferation. These opposite effects are also seen with inflammation, particularly with rheumatoid arthritis, and with asthma. DHA has a positive effect on diseases such as hypertension, arthritis, atherosclerosis, depression, adult-onset diabetes mellitus, myocardial infarction, thrombosis, and some cancers.

  14. Lysophosphatidylcholine acyltransferase 1 protects against cytotoxicity induced by polyunsaturated fatty acids. (United States)

    Akagi, Sosuke; Kono, Nozomu; Ariyama, Hiroyuki; Shindou, Hideo; Shimizu, Takao; Arai, Hiroyuki


    The degree of fatty acid unsaturation in membrane phospholipids affects many membrane-associated functions and can be influenced by dietary consumption of fatty acids such as saturated fatty acids and polyunsaturated fatty acids (PUFAs). Cells must adapt to changes in composition of membrane fatty acids by regulating lipid-metabolizing enzymes. In this study, we investigated how cells respond to loading with excess PUFAs, such as arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid. A lipidomics analysis revealed that dipalmitoylphosphatidylcholine (DPPC) was increased after the production of PUFA-containing phospholipids in cells loaded with PUFAs. An RNA interference screen of lipid-metabolizing enzymes revealed that lysophosphatidylcholine acyltransferase 1 (LPCAT1) was involved in the DPPC production. Moreover, LPCAT1 knockdown markedly enhanced the cytotoxicity induced by excess PUFAs. PUFA-induced cytotoxicity was dependent on caspase and unfolded protein response (UPR) sensor proteins inositol requiring 1α and protein kinase R-like endoplasmic reticulum kinase, suggesting that excess PUFAs trigger UPR-mediated apoptosis. In murine retina, in which PUFAs are highly enriched, DPPC was produced along with increase of PUFA-containing phospholipids. In LPCAT1 knockout mice, DPPC level was reduced and UPR was activated in the retina. Our results provide insight into understanding of the retinal degeneration seen in rd11 mice that lack LPCAT1.-Akagi, S., Kono, N., Ariyama, H., Shindou, H., Shimizu, T., Arai, H. Lysophosphatidylcholine acyltransferase 1 protects against cytotoxicity induced by polyunsaturated fatty acids.

  15. Oxidative stress and nucleic acid oxidation in patients with chronic kidney disease. (United States)

    Sung, Chih-Chien; Hsu, Yu-Chuan; Chen, Chun-Chi; Lin, Yuh-Feng; Wu, Chia-Chao


    Patients with chronic kidney disease (CKD) have high cardiovascular mortality and morbidity and a high risk for developing malignancy. Excessive oxidative stress is thought to play a major role in elevating these risks by increasing oxidative nucleic acid damage. Oxidative stress results from an imbalance between reactive oxygen/nitrogen species (RONS) production and antioxidant defense mechanisms and can cause vascular and tissue injuries as well as nucleic acid damage in CKD patients. The increased production of RONS, impaired nonenzymatic or enzymatic antioxidant defense mechanisms, and other risk factors including gene polymorphisms, uremic toxins (indoxyl sulfate), deficiency of arylesterase/paraoxonase, hyperhomocysteinemia, dialysis-associated membrane bioincompatibility, and endotoxin in patients with CKD can inhibit normal cell function by damaging cell lipids, arachidonic acid derivatives, carbohydrates, proteins, amino acids, and nucleic acids. Several clinical biomarkers and techniques have been used to detect the antioxidant status and oxidative stress/oxidative nucleic acid damage associated with long-term complications such as inflammation, atherosclerosis, amyloidosis, and malignancy in CKD patients. Antioxidant therapies have been studied to reduce the oxidative stress and nucleic acid oxidation in patients with CKD, including alpha-tocopherol, N-acetylcysteine, ascorbic acid, glutathione, folic acid, bardoxolone methyl, angiotensin-converting enzyme inhibitor, and providing better dialysis strategies. This paper provides an overview of radical production, antioxidant defence, pathogenesis and biomarkers of oxidative stress in patients with CKD, and possible antioxidant therapies.

  16. Oxidative Stress and Nucleic Acid Oxidation in Patients with Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Chih-Chien Sung


    Full Text Available Patients with chronic kidney disease (CKD have high cardiovascular mortality and morbidity and a high risk for developing malignancy. Excessive oxidative stress is thought to play a major role in elevating these risks by increasing oxidative nucleic acid damage. Oxidative stress results from an imbalance between reactive oxygen/nitrogen species (RONS production and antioxidant defense mechanisms and can cause vascular and tissue injuries as well as nucleic acid damage in CKD patients. The increased production of RONS, impaired nonenzymatic or enzymatic antioxidant defense mechanisms, and other risk factors including gene polymorphisms, uremic toxins (indoxyl sulfate, deficiency of arylesterase/paraoxonase, hyperhomocysteinemia, dialysis-associated membrane bioincompatibility, and endotoxin in patients with CKD can inhibit normal cell function by damaging cell lipids, arachidonic acid derivatives, carbohydrates, proteins, amino acids, and nucleic acids. Several clinical biomarkers and techniques have been used to detect the antioxidant status and oxidative stress/oxidative nucleic acid damage associated with long-term complications such as inflammation, atherosclerosis, amyloidosis, and malignancy in CKD patients. Antioxidant therapies have been studied to reduce the oxidative stress and nucleic acid oxidation in patients with CKD, including alpha-tocopherol, N-acetylcysteine, ascorbic acid, glutathione, folic acid, bardoxolone methyl, angiotensin-converting enzyme inhibitor, and providing better dialysis strategies. This paper provides an overview of radical production, antioxidant defence, pathogenesis and biomarkers of oxidative stress in patients with CKD, and possible antioxidant therapies.

  17. Generation of fad2 transgenic mice that produce omega-6 fatty acids

    Institute of Scientific and Technical Information of China (English)

    CHEN Qing; LIU Qing; WU ZhiFang; WANG ZongYi; GOU KeMian


    Fatty acid desaturase-2 (FAD2)introduces a double bond in position △12 in oleic acid (18:1)to form linoleic acid (18:2 n-6)in higher plants and microbes.A new transgenic expression cassette,containing CMV promoter/fad2 cDNA/SV40 polyA,was constructedto produce transgenic mice.Among 63 healthy offspring,10 founders (15.9%)integrated the cotton fad2 transgene into their genomes,as demonstrated by PCR and Southern blotting analysis.All founder mice were fertile and heterozygous fad2 female and nontransgenic littermates were used for fatty acid analysis using gas chromatography.One fad2 transgenic line showed substantial differences in the fatty acid profiles and the level of linoleic acid was increased 19% (P<0.05)in transgenic muscles compared to their nontransgenic littermates.Moreover,it exhibited an 87% and a 9% increase (P<0.05)in arachidonic acid (20:4 n-6)in muscles and liver,compared to their nontransgenic littermates.The results indicate that the plant fad2 gene can be functionally expressed in transgenic mice and may playan active role in conversion of oleic acid into linoleic acid.

  18. Generation of fad2 transgenic mice that produce omega-6 fatty acids

    Institute of Scientific and Technical Information of China (English)


    Fatty acid desaturase-2 (FAD2) introduces a double bond in position 12 in oleic acid (18:1) to form linoleic acid (18:2 n-6) in higher plants and microbes. A new transgenic expression cassette, containing CMV promoter/fad2 cDNA/SV40 polyA, was constructedto produce transgenic mice. Among 63 healthy offspring, 10 founders (15.9%) integrated the cotton fad2 transgene into their genomes, as demonstrated by PCR and Southern blotting analysis. All founder mice were fertile and heterozygous fad2 female and nontransgenic littermates were used for fatty acid analysis using gas chromatography. One fad2 transgenic line showed substantial differences in the fatty acid profiles and the level of linoleic acid was increased 19% (P<0.05) in transgenic muscles compared to their nontransgenic littermates. Moreover, it exhibited an 87% and a 9% increase (P<0.05) in arachidonic acid (20:4 n-6) in muscles and liver, compared to their nontransgenic littermates. The results indicate that the plant fad2 gene can be functionally expressed in transgenic mice and may playan active role in conversion of oleic acid into linoleic acid.

  19. Significance of long-chain polyunsaturated fatty acids (PUFAs) for the development and behaviour of children. (United States)

    Schuchardt, Jan Philipp; Huss, Michael; Stauss-Grabo, Manuela; Hahn, Andreas


    omega-6 and omega-3 polyunsaturated fatty acids (PUFAs) play a central role in the normal development and functioning of the brain and central nervous system. Long-chain PUFAs (LC-PUFAs) such as eicosapentaenoic acid (EPA, C20:5omega-3), docosahexaenoic acid (DHA, C22:6omega-3) and arachidonic acid (AA, C20:4omega-6), in particular, are involved in numerous neuronal processes, ranging from effects on membrane fluidity to gene expression regulation. Deficiencies and imbalances of these nutrients, not only during the developmental phase but throughout the whole life span, have significant effects on brain function. Numerous observational studies have shown a link between childhood developmental disorders and omega-6:omega-3 fatty acid imbalances. For instance, neurocognitive disorders such as attention-deficit hyperactivity disorder (ADHD), dyslexia, dyspraxia and autism spectrum disorders are often associated with a relative lack of omega-3 fatty acids. In addition to a high omega-6 fatty acid intake and, in many cases, an insufficient supply of omega-3 fatty acids among the population, evidence is increasing to suggest that PUFA metabolism can be impaired in individuals with ADHD. In this context, PUFA imbalances are being discussed as potential risk factors for neurodevelopmental disorders. Another focus is whether the nutritive PUFA requirements-especially long-chain omega-3 fatty acid requirements-are higher among some individuals. Meanwhile, several controlled studies investigated the clinical benefits of LC-PUFA supplementation in affected children and adolescents, with occasionally conflicting results.

  20. Folic acid (United States)

    ... taking folic acid by itself, or with L-carnitine a compound similar to an amino acid from ... levels. It is not clear if folic acid supplementation reduces hearing loss in people with normal folate ...

  1. Impact of methods used to express levels of circulating fatty acids on the degree and direction of associations with blood lipids in humans. (United States)

    Sergeant, Susan; Ruczinski, Ingo; Ivester, Priscilla; Lee, Tammy C; Morgan, Timothy M; Nicklas, Barbara J; Mathias, Rasika A; Chilton, Floyd H


    Numerous studies have examined relationships between disease biomarkers (such as blood lipids) and levels of circulating or cellular fatty acids. In such association studies, fatty acids have typically been expressed as the percentage of a particular fatty acid relative to the total fatty acids in a sample. Using two human cohorts, this study examined relationships between blood lipids (TAG, and LDL, HDL or total cholesterol) and circulating fatty acids expressed either as a percentage of total or as concentration in serum. The direction of the correlation between stearic acid, linoleic acid, dihomo-γ-linolenic acid, arachidonic acid and DHA and circulating TAG reversed when fatty acids were expressed as concentrations v. a percentage of total. Similar reversals were observed for these fatty acids when examining their associations with the ratio of total cholesterol:HDL-cholesterol. This reversal pattern was replicated in serum samples from both human cohorts. The correlations between blood lipids and fatty acids expressed as a percentage of total could be mathematically modelled from the concentration data. These data reveal that the different methods of expressing fatty acids lead to dissimilar correlations between blood lipids and certain fatty acids. This study raises important questions about how such reversals in association patterns impact the interpretation of numerous association studies evaluating fatty acids and their relationships with disease biomarkers or risk.

  2. A simple, rapid micromethod for the determination of the structure of unsaturated fatty acids via ozonolysis. (United States)

    Nickell, E C; Privett, O S


    A micromethod for the localization of double bonds in unsaturated fatty acids via ozonolysis employing pyrolytic cleavage of ozonides in the presence of a hydrogenation catalyst is described. Cleavage of the ozonides is carried out in a gasliquid chromatographie instrument in a small glass tube, containing the catalyst, inserted in the top of the column opposite the in input heaters at 225C. Ozonides of methyl esters of straight chain unsaturated fatty acids are cleaved through the action of the catalyst to aldehyde fragments which are swept simultaneously into the column for analysis.The double bond positions are deduced from the chain length of the fragments. The method is demonstrated on methyl oleate, linoleate, linolenate and arachidonate.

  3. Cardioprotective mechanism of omega-3 polyunsaturated fatty acids. (United States)

    Endo, Jin; Arita, Makoto


    Omega-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid and docosahexaenoic acid, are widely regarded as cardioprotective. Several large-scale, randomized clinical trials have shown that dietary intake of omega-3 PUFAs improves the prognosis of patients with symptomatic heart failure or recent myocardial infarction. Therefore, dietary consumption of omega-3 PUFA is recommended in international guidelines for the general population to prevent the occurrence of cardiovascular diseases (CVDs). However, the precise mechanisms underlying the cardioprotective effects of omega-3 PUFAs are not fully understood. Omega-3 PUFAs can be incorporated into the phospholipid bilayer of cell membranes and can affect membrane fluidity, lipid microdomain formation, and signaling across membranes. Omega-3 PUFAs also modulate the function of membrane ion channels, such as Na and L-type Ca channels, to prevent lethal arrhythmias. Moreover, omega-3 PUFAs also prevent the conversion of arachidonic acid into pro-inflammatory eicosanoids by serving as an alternative substrate for cyclooxygenase or lipoxygenase, resulting in the production of less potent products. In addition, a number of enzymatically oxygenated metabolites derived from omega-3 PUFAs were recently identified as anti-inflammatory mediators. These omega-3 metabolites may contribute to the beneficial effects against CVDs that are attributed to omega-3 PUFAs.

  4. Postnatal changes in fatty acids composition of brown adipose tissue (United States)

    Ohno, T.; Ogawa, K.; Kuroshima, A.


    It has been demonstrated that thermogenic activity of brown adipose tissue (BAT) is higher during the early postnatal period, decreasing towards a low adult level. The present study examined postnatal changes in the lipid composition of BAT. BAT from pre-weaning rats at 4 and 14 days old showed the following differences in lipid composition compared to that from adults of 12 weeks old. (i) Relative weight of interscapular BAT to body weight was markedly greater. (ii) BAT-triglyceride (TG) level was lower, while BAT-phospholipid (PL)level was higher. (iii) In TG fatty acids (FA) polyunsaturated fatty acids (PU; mol %), arachidonate index (AI), unsaturation index (UI) and PU/saturated FA (SA) were higher; rare FA such as eicosadienoate, bishomo- γ-linolenic acid and lignoceric acid in mol % were also higher. (iv) In PL-FA monounsaturated FA (MU) in mol % was lower; PU mol %, AI and UI were higher. These features in BAT of pre-weaning rats resembled those in the cold-acclimated adults, suggesting a close relationship of the PL-FA profile to high activity of BAT.

  5. Resistance of essential fatty acid-deficient rats to endotoxin-induced increases in vascular permeability

    Energy Technology Data Exchange (ETDEWEB)

    Li, E.J.; Cook, J.A.; Spicer, K.M.; Wise, W.C.; Rokach, J.; Halushka, P.V. (Medical Univ. of South Carolina, Charleston (USA))


    Resistance to endotoxin in essential fatty acid-deficient (EFAD) rats is associated with reduced synthesis of certain arachidonic acid metabolites. It was hypothesized that EFAD rats would manifest decreased vascular permeability changes during endotoxemia as a consequence of reduced arachidonic acid metabolism. To test this hypothesis, changes in hematocrit (HCT) and mesenteric localization rate of technetium-labeled human serum albumin (99mTc-HSA) and red blood cells (99mTc-RBC) were assessed in EFAD and normal rats using gamma-camera imaging. Thirty minutes after Salmonella enteritidis endotoxin, EFAD rats exhibited less hemoconcentration as determined by % HCT than normal rats. Endotoxin caused a less severe change in permeability index in the splanchnic region in EFAD rats than in normal rats (1.2 +/- 0.6 x 10(-3)min-1 vs. 4.9 +/- 1.7 x 10(-3)min-1 respectively, P less than 0.05). In contrast to 99mTc-HSA, mesenteric localization of 99mTc-RBC was not changed by endotoxin in control or EFAD rats. Supplementation with ethyl-arachidonic acid did not enhance susceptibility of EFAD rats to endotoxin-induced splanchnic permeability to 99mTc-HSA. Leukotrienes have been implicated as mediators of increased vascular permeability in endotoxin shock. Since LTC3 formation has been reported to be increased in EFA deficiency, we hypothesized that LTC3 may be less potent than LTC4. Thus the effect of LTC3 on mean arterial pressure and permeability was compared to LTC4 in normal rats. LTC3-induced increases in peak mean arterial pressure were less than LTC4 at 10 micrograms/kg (39 +/- 5 mm Hg vs. 58 +/- 4 mm Hg respectively, P less than 0.05) and at 20 micrograms/kg (56 +/- 4 mm Hg vs. 75 +/- 2 mm Hg respectively, P less than 0.05). LY171883 (30 mg/kg), an LTD4/E4 receptor antagonist, attenuated the pressor effect of LTC4, LTD4, and LTC3.

  6. Folic acid and polyunsaturated fatty acids improve cognitive function and prevent depression, dementia, and Alzheimer's disease--but how and why? (United States)

    Das, Undurti N


    Low blood folate and raised homocysteine concentrations are associated with poor cognitive function. Folic acid supplementation improves cognitive function. Folic acid enhances the plasma concentrations of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). EPA, DHA, and arachidonic acid (AA) are of benefit in dementia and Alzheimer's disease by up-regulating gene expression concerned with neurogenesis, neurotransmission and connectivity, improving endothelial nitric oxide (eNO) generation, enhancing brain acetylcholine levels, and suppressing the production of pro-inflammatory cytokines. EPA, DHA, and AA also form precursors to anti-inflammatory compounds such as lipoxins, resolvins, and neuroprotectin D1 (NPD1) that protect neurons from the cytotoxic action of various noxious stimuli. Furthermore, various neurotrophins and statins enhance the formation of NPD1 and thus, protect neurons from oxidative stress and prevent neuronal apoptosis Folic acid improves eNO generation, enhances plasma levels of EPA/DHA and thus, could augment the formation of NPD1. These results suggest that a combination of EPA, DHA, AA and folic acid could be of significant benefit in dementia, depression, and Alzheimer's disease and improve cognitive function.

  7. Separation and Identification of Fatty Acid in the Seed Oils of Two New Species of Celosia Cristata L.

    Institute of Scientific and Technical Information of China (English)

    WENG Debao; WANG Haifeng


    The seed oils of two new species of Celosia cristata L., C. Argentea L. Var. Crispa Kuntze (Yellow flower) and C. Cristata L. Cv. Spicata ( Red flower), were extracted with organic solvent and the fatty acides (Fas) in seed oils were separated and identificated by gas chromatography (GC). They all contained 10 kinds of FA including 4 trace Fas, respectively. Two new Fas of odd number of carbons in the seed oils, pentadecanoic acid( C15:0) and heptadecenoic acid (C17:1 ), were found. The compositions of main Fas in the seed oils were palmitic 20.61%, 23.50%; stearic 1.87 %; 2.39 %; oleic 20.77 %, 19.93% ;linoleic 51.39%, 45.99%; linolenic 1.54%, 1.86% and arachidonic 3.20%, 3.42%, respectively.

  8. The potential usage of caffeic acid phenethyl ester (CAPE) against chemotherapy-induced and radiotherapy-induced toxicity. (United States)

    Akyol, Sumeyya; Ginis, Zeynep; Armutcu, Ferah; Ozturk, Gulfer; Yigitoglu, M Ramazan; Akyol, Omer


    Protection of the patients against the side effects of chemotherapy and radiotherapy regimens has attracted increasing interest of clinicians and practitioners. Caffeic acid phenethyl ester (CAPE), which is extracted from the propolis of honeybee hives as an active component, specifically inhibits nuclear factor κB at micromolar concentrations and show ability to stop 5-lipoxygenase-catalysed oxygenation of linoleic acid and arachidonic acid. CAPE has antiinflammatory, antiproliferative, antioxidant, cytostatic, antiviral, antibacterial, antifungal and antineoplastic properties. The purpose of this review is to summarize in vivo and in vitro usage of CAPE to prevent the chemotherapy-induced and radiotherapy-induced damages and side effects in experimental animals and to develop a new approach for the potential usage of CAPE in clinical trial as a protective agent during chemotherapy and radiotherapy regimens.

  9. Synthesis and biological activities of transition metal complexes based on acetylsalicylic acid as neo-anticancer agents. (United States)

    Rubner, Gerhard; Bensdorf, Kerstin; Wellner, Anja; Kircher, Brigitte; Bergemann, Silke; Ott, Ingo; Gust, Ronald


    [(μ(4)-η(2))-(Prop-2-ynyl)-2-acetoxybenzoate]dicobalthexacarbonyl (Co-ASS), a derivative of aspirin (ASS), demonstrated high growth-inhibitory potential against various tumor cells with interference in the arachidonic acid cascade as probable mode of action. The significance of the kind of metal and cluster was verified in this structure-activity study: Co(2)(CO)(6) was respectively exchanged by a tetrameric cobalt-, trimeric ruthenium-, or trimeric ironcarbonyl cluster. Furthermore, the metal binding motif was changed from alkyne to 1,3-butadiene. Compounds were evaluated for growth inhibition, antiproliferative effects, and apoptosis induction in breast (MCF-7, MDA-MB 231) and colon cancer (HT-29) cell lines and for COX-1/2 inhibitory effects at isolated isoenzymes. Additionally, the major COX metabolite prostaglandin E2 (PGE(2)) was quantified in arachidonic acid-stimulated MDA-MB 231 breast tumor cells. It was demonstrated that the metal cluster was of minor importance for effects on cellular activity if an alkyne was used as ligand. Generally, no correlation existed between growth inhibition and COX activity. Cellular growth inhibition and antiproliferative activity at higher concentrations of the most active compounds Prop-ASS-Co(4) and Prop-ASS-Ru(3) correlated well with apoptosis induction.

  10. The Decrease of n-3 Fatty Acid Energy Percentage in an Equicaloric Diet Fed to B6C3Fe Mice for Three Generations Elicits Obesity

    Directory of Open Access Journals (Sweden)

    Ingeborg Hanbauer


    Full Text Available Feeding mice, over 3 generations, an equicaloric diet in which α-linolenic acid, the dietary precursor of n-3 polyunsaturated fatty acids, was substituted by linoleic acid, the dietary precursor of n-6 polyunsaturated fatty acids, significantly increased body weight throughout life when compared with standard diet-fed mice. Adipogenesis observed in the low n-3 fatty acid mice was accompanied by a 6-fold upregulation of stearyl-coenzyme A desaturase 1 (Scd1, whose activity is correlated to plasma triglyceride levels. In total liver lipid and phospholipid extracts, the sum of n-3 fatty acids and the individual longer carbon chain acids, eicosapentaenoic acid (20:5n3, docosapentaenoic acid (22:5n3, and docosahexaenoic acid (22:6n3 were significantly decreased whereas arachidonic acid (20:4n6 was significantly increased. In addition, low n-3 fatty acid-fed mice had liver steatosis, heart, and kidney hypertrophy. Hence, reducing dietary α-linolenic acid, from 1.02 energy% to 0.16 energy% combined with raising linoleic acid intake resulted in obesity and had detrimental consequences on organ function.

  11. Egg yolk as a source of long-chain polyunsaturated fatty acids in infant feeding. (United States)

    Simopoulos, A P; Salem, N


    In this paper we compare the fatty acid content of egg yolks from hens fed four different feeds as a source of docosahexaenoic acid to supplement infant formula. Greek eggs contain more docosahexaenoic acid (DHA, 22:6 omega 3) and less linoleic acid (LA, 18:2 omega 6) and alpha-linolenic acid (LNA, 18:3 omega 3) than do fish-meal or flax eggs. Two to three grams of Greek egg yolk may provide an adequate amount of DHA and arachidonic acid for a preterm neonate. Mean intake of breast milk at age 1 mo provides 250 mg long-chain omega 3 fatty acids. This amount can be obtained from less than 1 yolk of a Greek egg (0.94), greater than 1 yolk of flax eggs (1.6) and fish-meal eggs (1.4), or 8.3 yolks of supermarket eggs. With proper manipulation of the hens' diets, eggs could be produced with fatty acid composition similar to that of Greek eggs.

  12. Characteristics of fatty acid distribution is associated with colorectal cancer prognosis. (United States)

    Zhang, Junjie; Zhang, Lijian; Ye, Xiaoxia; Chen, Liyu; Zhang, Liangtao; Gao, Yihua; Kang, Jing X; Cai, Chun


    To investigate tissue fatty acid distribution in relation to the incidence of colorectal cancer prognosis, adjacent normal tissue and cancerous tissue from 35 samples of clinically incident colorectal cancer were obtained. Fatty acids were measured in the colorectal mucosa phospholipid fraction by gas chromatography mass spectrometry. Palmitoleic acid and oleic acid were significantly lower in colorectal cancerous tissue, ranging from 20% to 50% less than the adjacent normal tissue. The omega-6 (n-6) fatty acid family members (20:2, 20:3, 20:4 and 22:4) were higher by 1-3 fold in cancerous colorectal tissue. Contrary with the high level of n-6 fatty acids, about a 37% to 87% reduction in EPA and DHA was observed in colorectal cancerous tissue. A higher level of linoleic acid and arachidonic acid was detected in the C cancer stage than in the B cancer stage (pdistribution of colorectal tissue is strongly linked to the incidence of colorectal cancer. This study also provides scientific basis for identifying novel biomarkers for the diagnosis and treatment of cancer.

  13. Fish oil prevents essential fatty acid deficiency and enhances growth: clinical and biochemical implications. (United States)

    Strijbosch, Robert A M; Lee, Sang; Arsenault, Danielle A; Andersson, Charlotte; Gura, Kathleen M; Bistrian, Bruce R; Puder, Mark


    Fish oil, a rich source of omega-3 fatty acids, has never been used as the sole source of lipid in clinical practice for fear of development of essential fatty acid deficiency, as it lacks the believed requisite levels of linoleic acid, an omega-6 fatty acid. The objectives of this study were to establish biochemical standards for fish oil as the sole fat and to test the hypothesis that fish oil contains adequate amounts of omega-6 fatty acids to prevent essential fatty acid deficiency. Forty mice were divided into 2 groups that were either pair fed or allowed to eat ad libitum. In each group, 4 subgroups of 5 mice were fed 1%, 5%, and 10% fish oil diets by weight or a control soybean diet for 9 weeks. Blood was collected at 4 time points, and fatty acid analysis was performed. Food intake and weight status were monitored. All groups but the pair-fed 1% fish oil group gained weight, and the 5% fish oil group showed the highest caloric efficiency in both pair-fed and ad libitum groups. Fatty acid profiles for the 1% fish oil group displayed clear essential fatty acid deficiency, 5% fish oil appeared marginal, and 10% and soybean oil diets were found to prevent essential fatty acid deficiency. Fish oil enhances growth through higher caloric efficiency. We established a total omega-6 fatty acid requirement of between 0.30% and 0.56% of dietary energy, approximately half of the conventionally believed 1% as linoleic acid. This can presumably be attributed to the fact that fish oil contains not only a small amount of linoleic acid, but also arachidonic acid, which has greater efficiency to meet omega-6 fatty acid requirements.

  14. Echium oil: A valuable source of n-3 and n-6 fatty acids

    Directory of Open Access Journals (Sweden)

    MIR Miquel


    Full Text Available Echium oil is a vegetable oil of non-GMO plant origin extracted from the seeds of Echium plantagineum containing significant amounts of omega-3 fatty acid Stearidonic Acid (SDA and omega-6 acid γ-linolenic acid (GLA. Typical fatty acid composition of Echium oil is: Oleic acid (18:1 n-9 16%, Linoleic acid (LA, 18:2 n-6 19%, γ-linolenic acid (GLA, 18:3 n-610%, α-linolenic acid (ALA, 18:3 n-3 30% and Stearidonic acid (SDA, 18:4 n-3 13%. This natural ratio of fatty acids, trough their metabolism, deliver enhanced plasma concentrations of eicosapentaenoic (EPA, 20:5 n-3, docosapentaenoic (DPA, 22:5 n-3 and dihomo-γ-linolenic (DGLA, 20:3 n-6 acids without increasing the concentrations of arachidonic acid (AA, 20:4 n-6. GLA is commonly associated with the anti-inflammatory effects of oils such as evening primrose oil and borage oil. Supplementation with GLA can markedly increase serum AA with subsequent pro-inflammatory effects. The presence of stearidonic acid in echium oil prevents the accumulation of serum AA and AA-derived eicosanoids without preventing the accumulation of DGLA which is the real n-6 precursor of anti-inflammatory eicosanoids. SDA is an intermediate in the biosynthetic conversion of ALA to EPA. As SDA is the product of the rate-limiting ∆6-desaturase step and due the efficiency of the elongase and ∆5-desaturase steps, SDA is readily converted to EPA. SDA has the physiologic benefits of EPA, for instance, lowering the serum triglycerides in hypertriglyceridemic subjects. Therefore echium oil is a true alternative for vegetarians or those who do not eat fish, to benefit from the anti-inflammatory effects of omega-3 and omega-6 long chain polyunsaturated fatty acids.

  15. Dietary total fat and fatty acids intake, serum fatty acids and risk of breast cancer: A meta-analysis of prospective cohort studies. (United States)

    Cao, Yi; Hou, Lin; Wang, Weijing


    Results from prospective cohort studies on the association between dietary total fat and fatty acids intake and risk of breast cancer remain controversial. Pertinent prospective cohort studies were identified by a search of Embase and PubMed from inception to September 2015. Study-specific relative risks (RRs) with 95% confidence intervals were pooled using a random-effect model. Between-study heterogeneity and publication bias were assessed, and sensitivity analysis was conducted. Twenty-four independent studies on dietary total fat and fatty acids intake and seven studies on serum fatty acids were included. The pooled RR of breast cancer for the highest vs. lowest category of dietary total fat intake was 1.10 (1.02-1.19); however, no association was observed in studies adjusting for traditional risk factors of breast cancer. No association was observed between animal fat, vegetable fat, saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), n-3 PUFA, n-6 PUFA, eicosapentaenoic acid, docosahexaenoic acid, alpha-linolenic acid, oleic acid, linoleic acid and arachidonic acid and risk of breast cancer. The pooled RRs of breast cancer for the highest vs. lowest category of serum SFA, MUFA, PUFA, n-3 PUFA and n-6 PUFA were 1.00 (0.78-1.28), 1.41 (0.99-2.03), 0.59 (0.27-1.30), 0.81 (0.60-1.10) and 0.84 (0.60-1.18), respectively. Results from this meta-analysis suggested that dietary total fat and fatty acids might be not associated with risk of breast cancer.

  16. [Overexpression of four fatty acid synthase genes elevated the efficiency of long-chain polyunsaturated fatty acids biosynthesis in mammalian cells]. (United States)

    Zhu, Guiming; Saleh, Abdulmomen Ali Mohammed; Bahwal, Said Ahmed; Wang, Kunfu; Wang, Mingfu; Wang, Didi; Ge, Tangdong; Sun, Jie


    Three long-chain polyunsaturated fatty acids, docosahexaenoic acid (DHA, 22:6n-3), eicosapentaenoic acid (EPA, 20:5n-3) and arachidonic acid (ARA, 20:4n-6), are the most biologically active polyunsaturated fatty acids in the body. They are important in developing and maintaining the brain function, and in preventing and treating many diseases such as cardiovascular disease, inflammation and cancer. Although mammals can biosynthesize these long-chain polyunsaturated fatty acids, the efficiency is very low and dietary intake is needed to meet the requirement. In this study, a multiple-genes expression vector carrying mammalian A6/A5 fatty acid desaturases and multiple-genes expression vector carrying mammalian Δ6/Δ5 fatty acid desaturases and Δ6/Δ5 fatty acid elongases coding genes was used to transfect HEK293T cells, then the overexpression of the target genes was detected. GC-MS analysis shows that the biosynthesis efficiency and level of DHA, EPA and ARA were significantly increased in cells transfected with the multiple-genes expression vector. Particularly, DHA level in these cells was 2.5 times higher than in the control cells. This study indicates mammal possess a certain mechanism for suppression of high level of biosynthesis of long chain polyunsaturated fatty acids, and the overexpression of Δ6/Δ5 fatty acid desaturases and Δ6/Δ5 fatty acid elongases broke this suppression mechanism so that the level of DHA, EPA and ARA was significantly increased. This study also provides a basis for potential applications of this gene construct in transgenic animal to produce high level of these long-chain polyunsaturated fatty acid.

  17. Effect of a phytogenic additive on blood serum indicator levels and fatty acids profile in fattening turkeys meat

    Directory of Open Access Journals (Sweden)

    Branislav Gálik


    Full Text Available The aim of the study was to determine the effect of a phytogenic additive on blood serum indicator levels and fatty acids profile of breast, leg muscles and liver in fattening turkeys. The experiment was realized in private turkey farm and in the Department of Animal Nutrition, Faculty of Agrobiology and Food Resources, Slovak University of Agriculture in Nitra. A total of 300 clinically healthy female turkeys (broad-breasted white turkey, hybrid XL were used in the experiment. Female turkeys were randomly divided into two groups (150 pcs per each. In the control group, turkey were fed with standard complete feed mixtures for fattening, in the experimental group, standard diets from the beginning to 12th week were supplemented with the a blend of essential oils from origanum, anise and citrus fruits as well as a prebiotic rich fructooligosaccharides in dosage 1kg per 1000 kg of feed mixture. Fattening lasted 18 weeks. Blood serum was collected at the end of the experiment, during the slaughter of birds. Samples of breast and leg muscles, and liver for fatty acids composition evaluation were collected during birds dissection (10 samples per each group. After the 12 weeks of phytoadditive supplementation, a tendency of lower activity of serum alanine aminotransferase (53.963 vs. 3.499 U/L and aspartate aminotransferase (6.238 vs. 1.012 U/L in experimental group of turkeys was found (P0.01 content of cis-8,11,14-eicosadienoic and arachidonic acids. The phytoadditive supplementation significantly (P<0.01 decreased content of some unsaturated fatty acids in turkeys tissues, as well. In experimental group of turkey have been recorded lower level of elaidic and oleic acids in the breast muscle and cis-11,14-eicosadienoic and arachidonic acids in the liver, compare to birds from control group.

  18. Fish meal supplementation increases bovine plasma and luteal tissue omega-3 fatty acid composition. (United States)

    White, N R; Burns, P D; Cheatham, R D; Romero, R M; Nozykowski, J P; Bruemmer, J E; Engle, T E


    The objective of this experiment was to determine if dietary inclusion of fish meal would increase plasma and luteal tissue concentrations of eicosapentaenoic and docosahexaenoic acids. Seventeen nonlactating Angus cows (2 to 8 yr of age) were housed in individual pens and fed a corn silage-based diet for approximately 60 d. Diets were supplemented with fish meal at 5% DMI (a rich source of eicosapentaenoic acid and docosahexaenoic acid; n = 9 cows) or corn gluten meal at 6% DMI (n = 8 cows). Body weights and jugular blood samples were collected immediately before the initiation of supplementation and every 7 d thereafter for 56 d to monitor plasma n-3 fatty acid composition and BW. Estrous cycles were synchronized using 2 injections of PGF(2α) administered at 14-d intervals. The ovary bearing the corpus luteum was surgically removed at midcycle (between d 10 and 12) after estrus synchronization, which corresponded to approximately d 60 of supplementation. The ovary was transported to the laboratory, and approximately 1.5 g of luteal tissue was stored at -80°C until analyzed for n-3 fatty acid content. Initial and ending BW did not differ (P > 0.10) between cows supplemented with fish meal and those with corn gluten meal. Plasma eicosapentaenoic acid was greater (P < 0.05) beginning at d 7 of supplementation and docosahexaenoic was greater (P < 0.05) beginning at d 14 of supplementation for cows receiving fish meal. Luteal tissue collected from fish meal-supplemented cows had greater (P < 0.05) luteal n-3 fatty acids and reduced (P < 0.05) arachidonic acid and n-6 to n-3 ratio as compared with tissue obtained from cows supplemented with corn gluten meal. Our data show that fish meal supplementation increases luteal n-3 fatty acid content and reduces available arachidonic acid content, the precursor for PGF(2α). The increase in luteal n-3 fatty acids may reduce PGF(2α) intraluteal synthesis after breeding resulting in increased fertility in cattle.

  19. Differential regulation of hepatic transcription factors in the Wistar rat offspring born to dams fed folic acid, vitamin B12 deficient diets and supplemented with omega-3 fatty acids. (United States)

    Meher, Akshaya; Joshi, Asmita; Joshi, Sadhana


    Nutritional status of the mother is known to influence various metabolic adaptations required for optimal fetal development. These may be mediated by transcription factors like peroxisome proliferator activated receptors (PPARs), which are activated by long chain polyunsaturated fatty acids. The objective of the current study was to examine the expression of different hepatic transcription factors and the levels of global methylation in the liver of the offspring born to dams fed micronutrient deficient (folic acid and vitamin B12) diets and supplemented with omega-3 fatty acids. Female rats were divided into five groups (n = 8/group) as follows; control, folic acid deficient (FD), vitamin B12 deficient (BD) and omega-3 fatty acid supplemented groups (FDO and BDO). Diets were given starting from pre-conception and continued throughout pregnancy and lactation. Pups were dissected at the end of lactation. Liver tissues were removed; snap frozen and stored at -80°C. Maternal micronutrients deficiency resulted in lower (pacid (DHA) and arachidonic acid (ARA) as compared to the control group. Pup liver PPARα and PPARγ expression was lower (pfatty acids supplementation to this group normalized (pfatty acids supplementation to this group reduced (pfatty acid supplementation. Our novel findings suggest a role for omega-3 fatty acids in the one carbon cycle in influencing the hepatic expression of transcription factors in the offspring.

  20. Lipid Transport through the Fetoplacental Barrier by the Fatty Acid-Binding Proteins in Pregnant Women with Herpes Virus Infection in the third Trimester

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    Michael T. Lucenko, PhD, ScD


    Full Text Available In this study, the transport of the long chain polyunsaturated fatty acids (LCPUFAs from the lacunar blood through the syncytiotrophoblast of the placental villi to the fetal cord blood via a saturable protein-mediated mechanism by the heart-type fatty acid-binding proteins (H-FABPs has been examined. Exacerbation of the herpes simplex viruses (HSV-1 in the third trimester of gestation reduces the delivery of the fatty acid-binding proteins to the syncytiotrophoblast. During exacerbation of the HSV-1 infection, the selective transfer of the LCPUFAs across the syncytiotrophoblast basal plasma membrane into the fetal cord blood was observed. The supply of anti-inflammatory ω-3 PUFAs was reduced; however, the inflow of inflammatory arachidonic acid and other ω-6 PUFAs into the fetal blood was increased.

  1. The Association between Cerebral White Matter Lesions and Plasma Omega-3 to Omega-6 Polyunsaturated Fatty Acids Ratio to Cognitive Impairment Development

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    Michihiro Suwa


    Full Text Available Objective. Cerebral white matter hyperintensity (WMH with magnetic resonance imaging (MRI has a potential for predicting cognitive impairment. Serum polyunsaturated fatty acid (PUFA levels are important for evaluating the extent of atherosclerosis. We investigated whether abnormal PUFA levels affected WMH grading and cognitive function in patients without significant cognitive impairment. Methods. Atherosclerotic risk factors, the internal carotid artery (ICA plaque, and serum ratios of eicosapentaenoic to arachidonic acids (EPA/AA and docosahexaenoic to arachidonic acids (DHA/AA were assessed in 286 patients. The relationship among these risk factors, WMH, and cognitive function was evaluated using WMH grading and the Mini-Mental State Examination (MMSE. Results. The development of WMH was associated with aging, hypertension, ICA plaques, and a low serum EPA/AA ratio (<0.38, obtained as the median value but was not related to dyslipidemia, diabetes, smoking, and a low serum DHA/AA ratio (<0.84, obtained as the median value. In addition, the MMSE score deteriorated slightly with the progression of WMH (29.7 ± 1.0 compared to 28.4 ± 2.1, P<0.0001. Conclusions. The progression of WMH was associated with a low serum EPA/AA ratio and accompanied minimal deterioration in cognitive function. Sufficient omega-3 PUFA intake may be effective in preventing the development of cognitive impairment.

  2. A Δ-9 Fatty Acid Desaturase Gene in the Microalga Myrmecia incisa Reisigl: Cloning and Functional Analysis

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    Wen-Bin Xue


    Full Text Available The green alga Myrmecia incisa is one of the richest natural sources of arachidonic acid (ArA. To better understand the regulation of ArA biosynthesis in M. incisa, a novel gene putatively encoding the Δ9 fatty acid desaturase (FAD was cloned and characterized for the first time. Rapid-amplification of cDNA ends (RACE was employed to yield a full length cDNA designated as MiΔ9FAD, which is 2442 bp long in sequence. Comparing cDNA open reading frame (ORF sequence to genomic sequence indicated that there are 8 introns interrupting the coding region. The deduced MiΔ9FAD protein is composed of 432 amino acids. It is soluble and localized in the chloroplast, as evidenced by the absence of transmembrane domains as well as the presence of a 61-amino acid chloroplast transit peptide. Multiple sequence alignment of amino acids revealed two conserved histidine-rich motifs, typical for Δ9 acyl-acyl carrier protein (ACP desaturases. To determine the function of MiΔ9FAD, the gene was heterologously expressed in a Saccharomyces cerevisiae mutant strain with impaired desaturase activity. Results of GC-MS analysis indicated that MiΔ9FAD was able to restore the synthesis of monounsaturated fatty acids, generating palmitoleic acid and oleic acid through the addition of a double bond in the Δ9 position of palmitic acid and stearic acid, respectively.

  3. Determination of fatty acids percentages and profile extracted from cuttlefish of Iranian coasts of Persian Gulf and Oman Sea

    Institute of Scientific and Technical Information of China (English)

    Yosief Ali Asadpour


    Objective: To determine the fatty acid profile extracted from cuttlefish of Persian Gulf and Oman Sea, including Ancistrocheirus, Enoploteuthidae, Cranchiidae, Ommastrephidae and Loliginidae. Methods:Oil was extracted by the Bligh and Dyer method. The fatty acid profile of the oil was determined by gas chromatography. Results:The results showed that (13±5)% of wet weight of cuttlefish is oil. The results also showed that cuttlefish oil has 29.40% saturated fatty acids and 23.70% single-band unsaturated fatty acids, and the total value of the unsaturated multiple-band is 40.20%, the contents of arachidonic acid 2.78%, linolenic acid 3.10%, linoleic acid 5.20%, docosahexaenoic acid 15.40%, and eicosapentaenoic acid 9.60% out of the total fatty acids of the same may be mentioned. Conclusions:The results of the current study described that cuttlefish is considered for the first time as the new and rich source of omega-3 and omega-6.

  4. Maternal Plasma Phosphatidylcholine Fatty Acids and Atopy and Wheeze in the Offspring at Age of 6 Years

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    Katharine C. Pike


    Full Text Available Variation in exposure to polyunsaturated fatty acids (PUFAs might influence the development of atopy, asthma, and wheeze. This study aimed to determine whether differences in PUFA concentrations in maternal plasma phosphatidylcholine are associated with the risk of childhood wheeze or atopy. For 865 term-born children, we measured phosphatidylcholine fatty acid composition in maternal plasma collected at 34 weeks’ gestation. Wheezing was classified using questionnaires at 6, 12, 24, and 36 months and 6 years. At age of 6 years, the children underwent skin prick testing, fractional exhaled nitric oxide (FENO measurement, and spirometry. Maternal n-6 fatty acids and the ratio of n-3 to n-6 fatty acids were not associated with childhood wheeze. However, higher maternal eicosapentaenoic acid, docosahexaenoic acid, and total n-3 fatty acids were associated with reduced risk of non-atopic persistent/late wheeze (RR 0.57, 0.67 and 0.69, resp. P=0.01, 0.015, and 0.021, resp.. Maternal arachidonic acid was positively associated with FENO (P=0.024. A higher ratio of linoleic acid to its unsaturated metabolic products was associated with reduced risk of skin sensitisation (RR 0.82, P=0.013. These associations provide some support for the hypothesis that variation in exposure to n-6 and n-3 fatty acids during pregnancy influences the risk of childhood wheeze and atopy.

  5. Refsum disease diagnostic marker phytanic acid alters the physical state of membrane proteins of liver mitochondria. (United States)

    Schönfeld, P; Struy, H


    Phytanic acid (3,7,11,15-tetramethylhexadecanoic acid), a branched chain fatty acid accumulating in Refsum disease to high levels throughout the body, induces uncoupling of rat liver mitochondria similar to non-branched fatty acids (e.g. palmitic acid), but the contribution of the ADP/ATP carrier or the aspartate/glutamate carrier in phytanic acid-induced uncoupling is of minor importance. Possible deleterious effects of phytanic acid on membrane-linked energy coupling processes were studied by ESR spectroscopy using rat liver mitochondria and a membrane preparation labeled with the lipid-specific spin probe 5-doxylstearic acid (5-DSA) or the protein-specific spin probe MAL-TEMPO (4-maleimido-2,2,6, 6-tetramethyl-piperidine-1-oxyl). The effects of phytanic acid on phospholipid molecular dynamics and on the physical state of membrane proteins were quantified by estimation of the order parameter or the ratio of the amplitudes of the weakly to strongly immobilized MAL-TEMPO binding sites (W/S ratio), respectively. It was found, that phytanic acid (1) increased the mobility of phospholipid molecules (indicated by a decrease in the order parameter) and (2) altered the conformational state and/or the segmental mobility of membrane proteins (indicated by a drastic decrease in the W/S ratio). Unsaturated fatty acids with multiple cis-double bonds (e.g. linolenic or arachidonic acid), but not non-branched FFA (ranging from chain length C10:0 to C18:0), also decrease the W/S ratio. It is hypothesized that the interaction of phytanic acid with transmembrane proteins might stimulate the proton permeability through the mitochondrial inner membrane according to a mechanism, different to a protein-supported fatty acid cycling.

  6. Ligand specificity and conformational stability of human fatty acid-binding proteins. (United States)

    Zimmerman, A W; van Moerkerk, H T; Veerkamp, J H


    Fatty acid binding proteins (FABPs) are small cytosolic proteins with virtually identical backbone structures that facilitate the solubility and intracellular transport of fatty acids. At least eight different types of FABP occur, each with a specific tissue distribution and possibly with a distinct function. To define the functional characteristics of all eight human FABPs, viz. heart (H), brain (B), myelin (M), adipocyte (A), epidermal (E), intestinal (I), liver (L) and ileal lipid-binding protein (I-LBP), we studied their ligand specificity, their conformational stability and their immunological crossreactivity. Additionally, binding of bile acids to I-LBP was studied. The FABP types showed differences in fatty acid binding affinity. Generally, the affinity for palmitic acid was lower than for oleic and arachidonic acid. All FABP types, except E-FABP, I-FABP and I-LBP interacted with 1-anilinonaphtalene-8-sulphonic acid (ANS). Only L-FABP, I-FABP and M-FABP showed binding of 11-((5-dimethylaminonaphtalene-1-sulfonyl)amino)undecanoic acid (DAUDA). I-LBP showed increasing binding of bile acids in the order taurine-conjugated>glycine-conjugated>unconjugated bile acids. A hydroxylgroup of bile acids at position 7 decreased and at position 12 increased the binding affinity to I-LBP. The fatty acid-binding affinity and the conformation of FABP types were differentially affected in the presence of urea. Our results demonstrate significant differences in ligand binding, conformational stability and surface properties between different FABP types which may point to a specific function in certain cells and tissues. The preference of I-LBP (but not L-FABP) for conjugated bile acids is in accordance with a specific role in bile acid reabsorption in the ileum.

  7. Essential fatty acid intake and serum fatty acid composition among adolescent girls in central Mozambique. (United States)

    Freese, Riitta; Korkalo, Liisa; Vessby, Bengt; Tengblad, Siv; Vaara, Elina M; Hauta-alus, Helena; Selvester, Kerry; Mutanen, Marja


    Many African diets are low in fat but are currently changing because of nutrition transition. We studied fat and fatty acid (FA) intake and the essential fatty acid (EFA) status of adolescent girls (aged 14-19 years, n 262) in Zambezia Province, central Mozambique. A cross-sectional study was carried out in a city as well as in the towns and rural villages of a coastal and an inland district. Dietary intake and FA sources were studied in a 24 h dietary recall. FA compositions of cholesteryl esters and phospholipids of non-fasting serum samples were analysed by GLC. Fat intake was low (13-18 % of energy) in all areas. Coconut and palm oil were the main sources of fat, and soyabean oil and maize were the main sources of PUFA. Compared to Food and Agriculture Organization/WHO 2010 recommendations, intake of linoleic acid (LA, 18 : 2n-6) was inadequate in the coastal district, and intakes of n-3 PUFA were inadequate in all areas. FA compositions of serum lipids differed between areas. The proportions of LA tended to be highest in the city and lowest in the rural areas. The phospholipid mead (20 : 3n-9):arachidonic acid (20 : 4n-6) ratio did not indicate EFA insufficiency. LA proportions in phospholipids were low, but those of long-chain n-6 and n-3 PUFA were high in comparison with Western adolescents. To conclude, fat sources, FA intake and EFA status differed between adolescent girls living in different types of communities. Fat intake was low, but EFA insufficiency was not indicated.

  8. Eicosapentaenoic acid increases cytochrome P-450 2J2 gene expression and epoxyeicosatrienoic acid production via peroxisome proliferator-activated receptor γ in endothelial cells. (United States)

    Wang, Dahai; Hirase, Tetsuaki; Nitto, Takeaki; Soma, Masaaki; Node, Koichi


    ω-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have beneficial effects on cardiovascular diseases. Cytochrome P-450 (CYP) 2J2 that is expressed in endothelial cells metabolizes arachidonic acids to biologically active epoxyeicosatrienoic acids (EETs) that possess anti-inflammatory and anti-thrombotic effects. We studied the effects of EPA and DHA on the expression of CYP 2J2 mRNA by reverse transcription-polymerase chain reaction in cultured human umbilical vein endothelial cells and found that EPA, but not DHA, increased the expression of CYP 2J2 mRNA in a dose-dependent and a time-dependent manner. EPA-induced CYP 2J2 expression was significantly inhibited by pretreatment with a peroxisome proliferator-activated receptor (PPAR) γ antagonist, GW9662. EPA, but not DHA, caused a significant increase in cellular levels of 11,12-dihydroxyeicosatrienoic acid that is a stable metabolite of 11,12-EET, which was blocked by pretreatment with GW9662. These data demonstrate that EPA increases CYP 2J2 mRNA expression and 11,12-EET production via PPARγ in endothelial cells and indicate a novel protective role of EPA and PPARγ against vascular inflammation.

  9. Nutrigenomics and nutrigenetics of ω3 polyunsaturated fatty acids. (United States)

    Vanden Heuvel, John P


    Diets rich in ω3 polyunsaturated fatty acids (ω3-PUFAs) such as alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid are associated with decreased incidence and severity of several chronic diseases including cardiovascular disease (CVD) and cancer. At least some of the beneficial effects of these dietary fatty acids are via metabolites such as prostaglandins, leukotrienes, thromboxanes, and resolvins. The effects of ω3-PUFAs are in contrast to those of fatty acids with virtually identical structures, such as the ω6-PUFAs linoleic acid and arachidonic acid, and their corresponding metabolites. The purpose of this chapter is to discuss both the nutrigenomics (nutrient-gene interactions) and nutrigenetics (genetic variation in nutrition) of dietary fatty acids with a focus on the ω3-PUFAs (Gebauer et al., 2007(1)). Important in the biological response for these fatty acids or their metabolites are cognate receptors that are able to regulate gene expression and coordinately affect metabolic or signaling pathways associated with CVD and cancer. Four nuclear receptor (NR) subfamilies will be emphasized as receptors that respond to dietary and endogenous ligands: (1) peroxisome proliferator-activated receptors, (2) retinoid X receptors, (3) liver X receptors, and (4) farnesoid X receptor. In addition to the different responses elicited by varying structures of fatty acids, responses may vary because of genetic variation in enzymes that metabolize ω3- and ω6 fatty acids or that respond to them. In particular, polymorphisms in the fatty acid desaturases and the aforementioned NRs contribute to the complexity of nutritional effects seen with ω3-PUFAs. Following a brief introduction to the health benefits of ω3-PUFAs, the regulation of gene expression by these dietary fatty acids via NRs will be characterized. Subsequently, the effects of single-nucleotide polymorphisms (SNPs) in key enzymes involved in the metabolism and response to ω3-PUFAs will

  10. Associations of Whole Blood n-3 and n-6 Polyunsaturated Fatty Acids with Blood Pressure in Children and Adolescents – Results from the IDEFICS/I.Family Cohort (United States)

    Pala, Valeria; Russo, Paola; Risé, Patrizia; Moreno, Luis A.; De Henauw, Stefaan; Mehlig, Kirsten; Veidebaum, Toomas; Molnár, Denés; Tornaritis, Michael; Galli, Claudio; Ahrens, Wolfgang; Börnhorst, Claudia


    Background Polyunsaturated n-3 and n-6 polyunsaturated fatty acids (PUFA) are precursors of biologically active metabolites that affect blood pressure (BP) regulation. This study investigated the association of n-3 and n-6 PUFA and BP in children and adolescents. Methods In a subsample of 1267 children aged 2–9 years at baseline of the European IDEFICS (Identification and prevention of dietary- and lifestyle-induced health effects in children and infants) cohort whole blood fatty acids were measured by a validated gas chromatographic method. Systolic and diastolic BP was measured at baseline and after two and six years. Mixed-effects models were used to assess the associations between fatty acids at baseline and BP z-scores over time adjusting for relevant covariables. Models were further estimated stratified by sex and weight status. Results The baseline level of arachidonic acid was positively associated with subsequent systolic BP (β = 0.08, P = 0.002) and diastolic BP (β = 0.07, P<0.001). In thin/normal weight children, baseline alpha-linolenic (β = -1.13, P = 0.003) and eicosapentaenoic acid (β = -0.85, P = 0.003) levels were inversely related to baseline and also to subsequent systolic BP and alpha-linolenic acid to subsequent diastolic BP. In overweight/obese children, baseline eicosapentaenoic acid level was positively associated with baseline diastolic BP (β = 0.54, P = 0.005). Conclusions Low blood arachidonic acid levels in the whole sample and high n-3 PUFA levels in thin/normal weight children are associated with lower and therefore healthier BP. The beneficial effects of high n-3 PUFA on BP were not observed in overweight/obese children, suggesting that they may have been overlaid by the unfavorable effects of excess weight. PMID:27806134

  11. Fatty acid desaturase gene variants, cardiovascular risk factors, and myocardial infarction in the Costa Rica Study

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    Stella eAslibekyan


    Full Text Available Genetic variation in fatty acid desaturases (FADS has previously been linked to long-chain polyunsaturated fatty acids (PUFAs in adipose tissue and cardiovascular risk. The goal of our study was to test associations between six common FADS polymorphisms (rs174556, rs3834458, rs174570, rs2524299, rs174589, rs174627, adipose tissue fatty acids, intermediate cardiovascular risk factors, and nonfatal myocardial infarction (MI in a matched population based case-control study of Costa Rican adults (n=1756. Generalized linear models and multiple conditional logistic regression models were used to assess the associations of interest. Analyses involving intermediate cardiovascular risk factors and MI were also conducted in two replication cohorts, The Nurses’ Health Study (n=1200 and The Health Professionals Follow-Up Study (n=1295. In the Costa Rica Study, genetic variation in the FADS cluster was associated with a robust linear decrease in adipose gamma-linolenic, arachidonic, and eicosapentaenoic fatty acids, and significant or borderline significant increases in the eicosadienoic, eicosatrienoic, and dihomo-gamma-linolenic fatty acids. However, the associations with adipose tissue fatty acids did not translate into changes in inflammatory biomarkers, blood lipids, or the risk of MI in the discovery or the replication cohorts. In conclusion, fatty acid desaturase polymorphisms impact long-chain PUFA biosynthesis, but their overall effect on cardiovascular health likely involves multiple pathways and merits further investigation.

  12. Dietary unsaturated fatty acids differently affect catecholamine handling by adrenal chromaffin cells. (United States)

    Gomes, Andreia; Correia, Gustavo; Coelho, Marisa; Araújo, João Ricardo; Pinho, Maria João; Teixeira, Ana Luisa; Medeiros, Rui; Ribeiro, Laura


    Catecholamines (CA) play an important role in cardiovascular (CDV) disease risk. Namely, noradrenaline (NA) levels positively correlate whereas adrenaline (AD) levels negatively correlate with obesity and/or CDV disease. Western diets, which are tipically rich in Ω-6 fatty acids (FAs) and deficient in Ω-3 FAs, may contribute to the development of obesity, type 2 diabetes and/or coronary artery disease. Taking this into consideration and the fact that our group has already described that saturated FAs affect catecholamine handling by adrenal chromaffin cells, this work aimed to investigate the effect of unsaturated FAs upon catecholamine handling in the same model. Our results showed that chronic exposure to unsaturated FAs differently modulated CA cellular content and release, regardless of both FA series and number of carbon atoms. Namely, the Ω-6 arachidonic and linoleic acids, based on their effect on CA release and cellular content, seemed to impair NA and AD vesicular transport, whereas γ-linolenic acid selectively impaired AD synthesis and release. Within the Ω-9 FAs, oleic acid was devoid of effect, and elaidic acid behaved similarly to γ-linolenic acid. Eicosapentaenoic and docosahexaenoic acids (Ω-3 series) impaired the synthesis and release of both NA and AD. These results deserve attention and future development, namely, in what concerns the mechanisms involved and correlative effects in vivo.

  13. Fatty acid profile of the sea snail Gibbula umbilicalis as a biomarker for coastal metal pollution. (United States)

    Silva, Carla O; Simões, Tiago; Novais, Sara C; Pimparel, Inês; Granada, Luana; Soares, Amadeu M V M; Barata, Carlos; Lemos, Marco F L


    Metals are among the most common environmental pollutants with natural or anthropogenic origin that can be easily transferred through the food chain. Marine gastropods are known to accumulate high concentrations of these metals in their tissues. Gibbula umbilicalis ecological importance and abundant soft tissues, which enables extent biochemical assessments, makes this particular organism a potentially suitable species for marine ecotoxicological studies. Fatty acids are carbon-rich compounds that are ubiquitous in all organisms and easy to metabolize. Their biological specificity, relatively well-studied functions and importance, and the fact that they may alter when stress is induced, make fatty acids prospect biomarkers. This work aimed to assess fatty acid profile changes in the gastropod G. umbilicalis exposed to three metal contaminants. After a 168h exposure to cadmium, mercury, and nickel, the following lipid related endpoints were measured: total lipid content; lipid peroxidation; and fatty acid profile (FAP). The analysis of the FAP suggested an alteration in the fatty acid metabolism and indicated a link between metals exposure and homeoviscous adaptation and immune response. In particular, five fatty acids (palmitic, eicosatrienoic, arachidonic, eicosapentaenoic, and docosahexaenoic acids), demonstrated to be especially good indicators of G. umbilicalis responses to the array of metals used, having thus the potential to be used as biomarkers for metal contamination in this species. This work represents a first approach for the use of FAP signature as a sensitive and informative parameter and novel tool in environmental risk assessment (ERA) of coastal environments, using G. umbilicalis as model species.

  14. Gestation length and birth weight in relation to intake of marine n-3 fatty acids. (United States)

    Olsen, S F; Hansen, H S; Secher, N J; Jensen, B; Sandström, B


    It has been hypothesized that marine n-3 fatty acids ingested during pregnancy prolong duration of pregnancy and increase fetal growth rate in humans. By a combined self-administered questionnaire and interview applied in the 30th week of gestation we assessed dietary intake of marine n-3 fatty acids and energy in a population-based sample of 965 pregnant Danish women; in a random 14% subsample we also measured marine n-3 fatty acids relative to arachidonic acid (FA-ratio) in erythrocytes. Mean intake of marine n-3 fatty acids was 0.25 (95% range 0-0.75) g/d. We could detect no association between n-3 fatty acid intake and FA-ratio on the one hand, and gestation length, birth weight and birth length on the other. The analyses were adjusted for maternal height, prepregnant weight, parity and smoking. The conclusion from the study was that within the intake range of this population, marine n-3 fatty acids ingested in the weeks prior to the 30th week of pregnancy seem not to be a predictor of gestation length or fetal growth rate.

  15. 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.

  16. Glucose-stimulated acrolein production from unsaturated fatty acids. (United States)

    Medina-Navarro, R; Duran-Reyes, G; Diaz-Flores, M; Hicks, J J; Kumate, J


    Glucose auto-oxidation may be a significant source of reactive oxygen species (ROS), and also be important in the lipid peroxidation process, accompanied by the release of toxic reactive products. We wanted to demonstrate that acrolein can be formed directly and actively from free fatty acids in a hyperglycemic environment. A suspension of linoleic and arachidonic acids (2.5 mM) was exposed to different glucose concentrations (5, 10 and 15 mmol/L) in vitro. The samples were extracted with organic solvents, partitioned, followed at 255-267 nm, and analysed using capillary electrophoresis and mass spectroscopy. The total release of aldehydes significantly (P < 0.01) increased from 1.0 to 5.1, 8.3 and 13.1 micromol/L after 6 hours of incubation, proportional to glucose concentrations. It was possible to verify a correlate hydroperoxide formation as well. Among the lipid peroxidation products, acrolein (5% of total) and its condensing product, 4-hydroxy-hexenal, were identified. From the results presented here, it was possible to demonstrate the production of acrolein, probably as a fatty acid product, due to free radicals generated from the glucose auto-oxidation process. The results led us to propose that acrolein, which is one of the most toxic aldehydes, is produced during hyperglycemic states, and may lead to tissue injury, as one of the initial problems to be linked to high levels of glucose in vivo.

  17. Valproic Acid (United States)

    ... acid is in a class of medications called anticonvulsants. It works by increasing the amount of a ... older (about 1 in 500 people) who took anticonvulsants such as valproic acid to treat various conditions ...

  18. Ascorbic Acid (United States)

    Ascorbic acid is used to prevent and treat scurvy, a disease caused by a lack of vitamin C ... Ascorbic acid comes in extended-release (long-acting) capsules and tablets, lozenges, syrup, chewable tablets, and liquid drops ...

  19. Amino acids (United States)

    ... this page: // Amino acids To use the sharing features on this page, please enable JavaScript. Amino acids are organic compounds that combine to form proteins . ...

  20. Analysis of epoxyeicosatrienoic and monohydroxyeicosatetraenoic acids esterified to phospholipids in human red blood cells by electrospray tandem mass spectrometry. (United States)

    Nakamura, T; Bratton, D L; Murphy, R C


    Electrospray ionization (ESI) and tandem mass spectrometry (MS/MS) were used to analyze epoxyeicosatrienoic acids (EETs) and monohydroxyeicosatetraenoic acids (HETEs) isolated from human red blood cell membranes following base hydrolysis. ESI results in the formation of an abundant isobaric carboxylate anion at m/z 319 for both of these oxidized metabolites of arachidonic acid. The product ion spectra from the collision-induced dissociation of this carboxylate anion could be used to identify each of the isomeric eicosanoids from the unique fragment ions of each eicosanoid. The observed product ion spectra were identical with those previously obtained by fast atom bombardment ionization; however, ESI required less EET and HETE for analysis. Both EET and HETE phospholipids were present in human red blood cells (RBCs) and their abundance could be substantially increased by treatment under conditions that would induce free radical oxidation of membrane phospholipids. Following incubation of human RBCs with tert-butyl hydroperoxide (tBuOOH), phospholipids were extracted and purified by normal-phase high-performance liquid chromatography (HPLC) as to glycerophospholipid class containing ethanolamine (GPE), serine (GPS) and choline (GPC) as the polar head group. Each class of phospholipid was hydrolyzed to yield the free carboxylic acid prior to on-line HPLC/ESI-MS/MS analysis. The formation of oxidized arachidonic acid esterified to phospholipids in treated RBCs was found to increase significantly for both esterified EETs in GPE, GPS and GPC which increased 49-, 34- and 59-fold, respectively, and also for esterified HETEs in GPE, GPS and GPC which increased 3-, 4- and 11-fold, respectively, compared with untreated RBCs. These results provide the first characterization of EETs formed non-enzymatically as intact phospholipids in a lipid peroxidation model system.

  1. Characterization of the ovary fatty acids composition of Rhamdia quelen (Quoy & Gaimard (Teleostei: Siluriformes, throughout their reproductive cycle

    Directory of Open Access Journals (Sweden)

    Rodrigo Vargas Anido

    Full Text Available Knowledge about gonad fatty acid composition is important for broodstock diet formulation. This study characterized ovary fatty acid composition of wild female jundiá catfish (Rhamdia quelen in their different gonadal maturation stages. Female jundiá (n = 36, average weight= 383.8 + 208.8 g were captured in the rio Uruguay, comprising all seasons. Ovaries were extracted and classified according to their gonadal maturation stage. Gonad-somatic ratio varied significantly among seasons, being higher in spring (3.7, followed by summer (2.2, winter (0.9 and autumn (0.6. Main fatty acids groups detected were: saturated (SFA= 35.5%, monounsaturated (MUFA= 28.1% and polyunsaturated fatty acids (PUFA= 33.5%. Over the four seasons, palmitic acid was recorded in large quantities, followed by docosahexaenoic acid (DHA and arachidonic acid (ARA. ARA was present in higher concentrations in immature or maturing ovaries, and its content decreased along the maturation process. Conversely, DHA and eicosapentaenoic acid (EPA contents increased during maturation. Such variation resulted in an increase in EPA/ARA and DHA/ARA ratios in mature gonads, which can be important for successful breeding. Such findings suggest that jundiá broodstock diets should contain lipids that provide long chain polyunsaturated fatty acids from both the n-3 and n-6 series to ensure gonadal maturation completion.

  2. Fatty acids - trans fatty acids (United States)

    The data supporting a negative effect of dietary trans fatty acids on cardiovascular disease risk is consistent. The primary dietary sources of trans fatty acids include partially hydrogenated fat and rudiment fat. The adverse effect of trans fatty acids on plasma lipoprotein profiles is consisten...

  3. Omega-3 fatty acids and antioxidants in edible wild plants. (United States)

    Simopoulos, Artemis P


    Human beings evolved on a diet that was balanced in the omega-6 and omega-3 polyunsaturated fatty acids (PUFA), and was high in antioxidants. Edible wild plants provide alpha-linolenic acid (ALA) and higher amounts of vitamin E and vitamin C than cultivated plants. In addition to the antioxidant vitamins, edible wild plants are rich in phenols and other compounds that increase their antioxidant capacity. It is therefore important to systematically analyze the total antioxidant capacity of wild plants and promote their commercialization in both developed and developing countries. The diets of Western countries have contained increasingly larger amounts of linoleic acid (LA), which has been promoted for its cholesterol-lowering effect. It is now recognized that dietary LA favors oxidative modification of low density lipoprotein (LDL) cholesterol and increases platelet response to aggregation. In contrast, ALA intake is associated with inhibitory effects on the clotting activity of platelets, on their response to thrombin, and on the regulation of arachidonic acid (AA) metabolism. In clinical studies, ALA contributed to lowering of blood pressure, and a prospective epidemiological study showed that ALA is inversely related to the risk of coronary heart disease in men. Dietary amounts of LA as well as the ratio of LA to ALA appear to be important for the metabolism of ALA to longer-chain omega-3 PUFAs. Relatively large reserves of LA in body fat. as are found in vegans or in the diet of omnivores in Western societies, would tend to slow down the formation of long-chain omega-3 fatty acids from ALA. Therefore, the role of ALA in human nutrition becomes important in terms of long-term dietary intake. One advantage of the consumption of ALA over omega-3 fatty acids from fish is that the problem of insufficient vitamin E intake does not exist with high intake of ALA from plant sources.

  4. [Changes in prostaglandin systhetase activity in mouse tissues as affected by S-[N-(3-aminopropyl)-2-aminoethyl] thiophosphoric acid]. (United States)

    Prianishnikova, E N; Zhulanova, Z I; Romantsev, E F


    Effect of various concentrations of a radioprotector S-[N-(3 aminopropyl)-2-aminoethyl] thiophosphoric acid on the activity of prostaglandine synthetase was studied in mouse liver microsomes as well as in the soluble fractions of testicules and brain in vitro. The activity of prostaglandine synthetase was estimated by monitoring the formation of labelled PGF2 alpha and PGE2 from I-14C-arachidonic acid. The radioprotector at concentration 1.66 mg/ml stimulated formation of PGF2 alpha in all the tissues studied. At the lower concentrations of the radioprotector only slight stimulation of the biosynthesis of prostaglandines in testicules was noted. No effect on their synthesis in the brain soluble fraction could be observed while in the liver microsomes it was inhibited. The radioprotective substance studied apparently affected the cyclooxygenase activity, which is a key enzyme in the prostaglandine-synthesizing system.

  5. Design, synthesis and evaluation of semi-synthetic triazole-containing caffeic acid analogues as 5-lipoxygenase inhibitors. (United States)

    De Lucia, Daniela; Lucio, Oscar Méndez; Musio, Biagia; Bender, Andreas; Listing, Monika; Dennhardt, Sophie; Koeberle, Andreas; Garscha, Ulrike; Rizzo, Roberta; Manfredini, Stefano; Werz, Oliver; Ley, Steven V


    In this work the synthesis, structure-activity relationship (SAR) and biological evaluation of a novel series of triazole-containing 5-lipoxygenase (5-LO) inhibitors are described. The use of structure-guided drug design techniques provided compounds that demonstrated excellent 5-LO inhibition with IC50 of 0.2 and 3.2 μm in cell-based and cell-free assays, respectively. Optimization of binding and functional potencies resulted in the identification of compound 13d, which showed an enhanced activity compared to the parent bioactive compound caffeic acid 5 and the clinically approved zileuton 3. Compounds 15 and 16 were identified as lead compounds in inhibiting 5-LO products formation in neutrophils. Their interference with other targets on the arachidonic acid pathway was also assessed. Cytotoxicity tests were performed to exclude a relationship between cytotoxicity and the increased activity observed after structure optimization.

  6. Biological effects of add-on eicosapentaenoic acid supplementation in diabetes mellitus and co-morbid depression

    DEFF Research Database (Denmark)

    Mocking, Roel J T; Assies, Johanna; Bot, Mariska;


    ) lipoprotein parameters during 12-weeks' follow-up. RESULTS: Besides increases in supplemented α-tocopherol [estimate (95% CI); 3.62 (1.14-6.11) µmol/l; p = 0.006] and plasma and erythrocyte EPA, the intervention did not influence other oxidative stress, inflammatory or one-carbon-cycle parameters compared...... to placebo. HPA-axis reactivity significantly decreased in the EPA-group (N = 12) [AUC(i): -121.93 (-240.20--3.47) min×nmol/l; p = 0.045], not in the placebo-group (N = 12). Furthermore, EPA-supplementation increased erythrocyte and plasma docosapentaenoic acid, and decreased plasma arachidonic acid (AA...

  7. Fatty acid metabolism in infants with functional and inflamatory bowel diseases

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    Marushko RV


    Full Text Available Summary. Over past years, considerable attention is paid to the role of fatty acids, especially polyunsaturated, in the development of various gastrointestinal diseases, among which the most common are functional and inflammatory bowel diseases. The need for studies of fatty acid disorders is to clarify the pathogenetic mechanisms in which fatty acids participate in the development intestinal pathology. The aim of this study to elaborate the optimal preventive and therapeutic measures to reduce the incidence of these diseases and provide the effective treatment, especially in early childhood . Objective: To study the profile features of fatty acids in infants with functional and inflammatory bowel diseases. Patients and methods: Were examined 149 children aged from 6 months to 3 years, divided into 3 groups: 52 children with chronic non-ulcerative non-specific colitis, 49 children with functional constipation and 47 children with functional diarrhea. Verification of diagnoses was provided in accordance with the «Standardised cinical protocols of medical care for children with digestive diseases». Analysis of fatty acid's profile was evaluated by the method blood gas chromatography. Results: All the examined children had fatty acid disorders. The level of saturated fatty acids was decreased and the concentration of polyunsaturated fatty acids was increased in the expence of omega 6 polyunsaturated fatty acids (PUFA, in particularly, linoleic and arachidonic acids. The greatest changes were observed in patients with chronic non-ulcerative non-specific colitis which can be considered as important links in the pathogenesis of chronic inflammation. In functional bowel disorders imbalance of fatty acids is likely to be a risk factor in development significant lesions in the intestinal mucosa. Conclusions: Given the presence of lipid imbalance in inflammatory bowel disease as well as in intestinal functional disorders, which is characterized by a

  8. Synthesis of structured lipid enriched with omega fatty acids and sn-2 palmitic acid by enzymatic esterification and its incorporation in powdered infant formula. (United States)

    Nagachinta, Supakana; Akoh, Casimir C


    Structured lipid (SL) enriched with arachidonic (ARA) and docosahexaenoic (DHA) acids was produced from tripalmitin using Lipozyme TL IM. The effects of acyl donors, that is, free fatty acids vs fatty acid ethyl esters, on the reactions were compared. The highest total incorporation of ARA and DHA was obtained when the reaction continued for 24 h, at a substrate mole ratio of 9, using free fatty acids as acyl donors (acidolysis). The SL prepared by a large-scale acidolysis reaction contained 17.69 ± 0.09% total ARA, 10.75 ± 0.15% total DHA, and 48.53 ± 1.40% sn-2 palmitic acid. SL thermograms exhibited multiple peaks indicating complexity of the triacylglycerol (TAG) distribution. RP-HPLC analysis of SL revealed nine of 26 TAG molecular species that were similar to those of human milk fat. Powdered infant formulas containing the SL were prepared by wet-mixing/spray-drying and dry-blending methods. Formula prepared with microencapsulated SL and the dry-blending method had better oxidative stability and color quality.

  9. Long-term treatment with the pan-PPAR agonist tetradecylthioacetic acid or fish oil is associated with increased cardiac content of n-3 fatty acids in rat

    Directory of Open Access Journals (Sweden)

    Strand Elin


    Full Text Available Abstract Background Excess peroxisome proliferator-activated receptor (PPAR stimulation has been associated with detrimental health effects including impaired myocardial function. Recently, supplementation with n-3 polyunsaturated fatty acids (PUFA has been associated with improved left ventricular function and functional capacity in patients with dilated cardiomyopathy. We investigated the long-term effects of the pan-PPAR agonist tetradecylthioacetic acid (TTA and/or high-dose fish oil (FO on cardiac fatty acid (FA composition and lipid metabolism. Male Wistar rats were given one out of four different 25% (w/v fat diets: control diet; TTA diet; FO diet; or diet containing both TTA and FO. Results After 50 weeks n-3 PUFA levels were increased by TTA and FO in the heart, whereas liver levels were reduced following TTA administration. TTA was associated with a decrease in arachidonic acid, increased activities of carnitine palmitoyltransferase II, fatty acyl-CoA oxidase, glycerol-3-phosphate acyltransferase, and fatty acid synthase in the heart. Furthermore, cardiac Ucp3 and Cact mRNA was upregulated. Conclusions Long-term treatment with the pan-PPAR agonist TTA or high-dose FO induced marked changes in PUFA composition and enzymatic activity involved in FA metabolism in the heart, different from liver. Changes included increased FA oxidation and a selective increase in cardiac n-3 PUFA.

  10. Clinical overview of effects of dietary long-chain polyunsaturated fatty acids during the perinatal period. (United States)

    Scholtz, Susan A; Colombo, John; Carlson, Susan E


    The current report provides a brief background introducing 30 years of research on long-chain polyunsaturated fatty acids (LC-PUFA) and infant development, but focuses mainly on challenges for future studies. Infants fed formulas containing only vegetable fats were found to have lower docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (20:4n-6) status than infants fed human milk. Studies soon focused on efforts to improve LC-PUFA status and evaluate functions suggested by early primate studies of DHA deficiency. Despite evidence for the importance of these fatty acids for development, particularly DHA, several recent meta-analyses conclude dietary supplementation does not enhance development. Future studies should employ (1) more finely grained measures of brain development as opposed to global measures, and (2) tests that evaluate development later in childhood when children are able to be tested on more complex behaviors (if found effective these would also be evidence of early brain programming). (3) Studies are needed to understand the cause of high variability in transfer of DHA to the fetus. (4) Finally, the role of single-nucleotide polymorphisms of the fatty acid desaturase genes 1 and 2 of mother and infant needs study to determine how they affect requirements for these fatty acids by the fetus/infant.

  11. Effect of age, season and housing system on cholesterol and fatty acids contents of table eggs

    Directory of Open Access Journals (Sweden)

    A. A. Hussein


    Full Text Available A survey was carried out in Khartoum State to examine the effects of hens' age (66, 42 and 20 weeks, season of production (winter and summer and housing system (open sided and closed on table egg contents of cholesterol and fatty acids. Eggs were collected and analyzed for cholesterol and fatty acids content using gas chromatography mass spectrometer. Eggs of 66 weeks old hens had a significantly (P<0.05 higher amount of cholesterol than eggs of 20 weeks and 42 weeks old ones. Eggs collected in winter season contained significantly (P<0.05 higher percentages of C16:19e fatty acid and vaccenic acid. Arachidonic acid was significantly (P<0.05 less in egg yolk of 66 weeks old hens. There were some variations in fatty acids level among all studied factors but the differences were not statistically significant. It could be concluded that eggs produced from younger hens contain less cholesterol than that of the older hens.

  12. Autistic Children Exhibit Decreased Levels of Essential Fatty Acids in Red Blood Cells

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    Sarah A. Brigandi


    Full Text Available Omega-6 (n-6 and omega-3 (n-3 polyunsaturated fatty acids (PUFA are essential nutrients for brain development and function. However, whether or not the levels of these fatty acids are altered in individuals with autism remains debatable. In this study, we compared the fatty acid contents between 121 autistic patients and 110 non-autistic, non-developmentally delayed controls, aged 3–17. Analysis of the fatty acid composition of red blood cell (RBC membrane phospholipids showed that the percentage of total PUFA was lower in autistic patients than in controls; levels of n-6 arachidonic acid (AA and n-3 docosahexaenoic acid (DHA were particularly decreased (p < 0.001. In addition, plasma levels of the pro-inflammatory AA metabolite prostaglandin E2 (PGE2 were higher in a subset of the autistic participants (n = 20 compared to controls. Our study demonstrates an alteration in the PUFA profile and increased production of a PUFA-derived metabolite in autistic patients, supporting the hypothesis that abnormal lipid metabolism is implicated in autism.

  13. [Anti-inflammatory effect of Urtica dioica folia extract in comparison to caffeic malic acid]. (United States)

    Obertreis, B; Giller, K; Teucher, T; Behnke, B; Schmitz, H


    Urtica dioica extract is a traditionary used adjuvant therapeutic in rheumatoid arthritis. The antiphlogistic effects of the urtica dioica folia extract IDS 23 (Extractum Urticae dioicae foliorum) and the main phenolic ingredient caffeic malic acid were tested concerning the inhibitory potential on biosynthesis of arachidonic acid metabolites in vitro. The caffeic malic acid was isolated from Urtica folia extract using gel exclusion- and high performance liquid chromatography and identified by mass spectroscopy and nuclear magnetic resonance. Concerning the 5-lipoxygenase products IDS 23 showed a partial inhibitory effect. The isolated phenolic acid inhibited the synthesis of the leukotriene B4 in a concentration dependent manner. The concentration for halfmaximal inhibition (IC50) was 83 microns/ml in the used assay. IDS 23 showed a strong concentration dependent inhibition of the synthesis of cyclooxygenase derived reactions. The IC50 were 92 micrograms/ml for IDS 23 and 38 micrograms/ml for the caffeic malic acid. Calculating the content in IDS 23 the caffeic malic acid is a possible but not the only active ingredient of the plant extract in the tested assay systems. It is demonstrated that the phenolic component showed a different enzymatic target compared with IDS 23. The antiphlogistic effects observed in vitro may give an explanation for the pharmacological and clinical effects of IDS 23 in therapie of rheumatoid diseases.

  14. Release of arachidonic acid metabolites from bloodby cultivation of human amniotic fluid with oneself blood%羊水与自体血培养后刺激花生四烯酸代谢物的释放

    Institute of Scientific and Technical Information of China (English)

    杨鉴; 余艳红; 周凤琴; 钟梅


    AIM: To investigate the effect of human amniotic fluid on the release of thromboxane A2 (TXA2), prostaglandin I2 (PGI2) and Leukotriene C4 (LTC4) from blood cells. METHODS: 1 mL human amniotic fluid and 10 mL oneself blood collected from 38 - 41 weeks with cesarean section were cultured at 37℃ for 30 min, and then centrifuged. The supernatants were taken and stored at - 70℃. TXB2 and 6 - Keto - PGF1α of the supernrants were determined by radioimmunoassay and LTC4 by enzyme immunoassay. RESULTS: It was found that the levels of TXB2 and LTC4 in blood were elevated from (63.5 + 52.0) ng/L and (40.1 + 39.2) ng/L to (189.1 + 102.0) ng/L and (293.5 + 206.1) ng/L respectively ( P 0.05 ). CONCLUSION: Amniotic fluid might stimulate the release of TXA2 and LTC4 from blood, it might affect the balance of TXA2 and PGI2 in blood, which might play an important role in the pathogenesis of amniotic fluid embolism.%目的:探讨人羊水在体外刺激自体血细胞释放前列环素(PGI2)、血栓素A2(TXA2)和白三烯C4(LTC4)等花生四烯酸代谢物的作用。方法:取产妇羊水与自体血进行培养,用放射免疫分析法检测血中血栓素B2(TXB2)和6-酮前列腺素F1α(6-Keto-PGF1α)的含量,用酶联免疫法检测LTC4。结果:羊水能刺激血细胞释放TXA2和LTC4,胎粪污染的羊水作用更为明显。TXB2的含量由加羊水培养前的(63.5±52.0)ne/L增加到培养后的(189.1±l02.0)ng/L(P0.05)。结论:羊水能刺激血细胞释放花生四烯酸类生物活性物质,使其正常的平衡状态被破坏,可能与羊水栓塞的发生机理有关。

  15. Simultaneous Determination Method of Epoxyeicosatrienoic Acids and Dihydroxyeicosatrienoic Acids by LC-MS/MS System. (United States)

    Mukai, Yuji; Toda, Takaki; Takeuchi, Satoya; Senda, Asuna; Yamashita, Miki; Eliasson, Erik; Rane, Anders; Inotsume, Nobuo


    Epoxyeicosatrienoic acids (EETs) are produced primarily by CYPs from arachidonic acid (AA) and then further metabolized to the corresponding dihydroxyeicosatrienoic acids (DHETs). EETs play important roles in physiological processes such as regulating vasodilation and inflammation. Thus, the drug inhibition of CYP-mediated AA metabolism could reduce production of EETs, potentially resulting in adverse cardiovascular events. The aim of this study was to develop a simple method to simultaneously determine the concentrations of both EETs and DHETs using a conventional LC-MS/MS system to evaluate drug-endogenous substance interactions, including eicosanoids. Eight eicosanoids (5,6-EET, 8,9-EET, 11,12-EET, 14,15-EET, 5,6-DHET, 8,9-DHET, 11,12-DHET, and 14,15-DHET) were detected with their corresponding deuterium-labeled eicosanoids as internal standards. The samples were purified by solid-phase extraction columns. Liquid chromatographic separation was achieved on a C18 column. DHETs and EETs were eluted at 4-7 and 18-26 min, respectively. The weighted (1/y(2)) calibration curves were linear over a range of 5-2000 nmol/L for EETs and 2-2000 nmol/L for DHETs. In quality control (QC) samples, the recoveries of eicosanoids were 95.2-118%. The intra-day precisions were within 6% in all three QC samples, and the inter-day precisions were eicosanoid levels in samples from incubation studies of AA by using human recombinant CYP enzyme (rCYP), and confirmed that the method has sensitivity sufficient for assessment of rCYP incubation study.

  16. Cardiac mortality is associated with low levels of omega-3 and omega-6 fatty acids in the heart of cadavers with a history of coronary heart disease. (United States)

    Chattipakorn, Nipon; Settakorn, Jongkolnee; Petsophonsakul, Petnoi; Suwannahoi, Padiphat; Mahakranukrauh, Pasuk; Srichairatanakool, Somdet; Chattipakorn, Siriporn C


    The benefits of omega-3 (ie, eicosapentaenoic acid and docosahexaenoic acid [DHA]) and omega-6 (ie, linoleic acid and arachidonic acid [AA]) fatty acids on reducing cardiac mortality are still debated. In this study, we tested the hypothesis that high levels of omega-3 and omega-6 fatty acids in heart tissues are associated with low cardiac mortality in Thai cadavers. One hundred fresh cadavers were examined in this study. The cause of death, history of coronary heart disease (CHD), and fish consumption habits were obtained from death certificates, cadaver medical record profiles, and a questionnaire to a person who lived with the subject before death. In each cadaver, biopsies of cardiac tissues were taken from the interventricular septum for measurement of fatty acid. Of the 100 cadavers (aver