Showing papers on "Docosahexaenoic acid published in 1982"

Brain Cortical Fatty Acids and Phospholipids During and Following Complete and Severe Incomplete Ischemia

Abstract: To explore the possibility that peroxtdative degradation of brain tissue lipid constituents is an important mechanism of irreversible ischemic damage, we measured cortical fatty acids and phospholipids during reversible brain ischemia in the rat. Neither complete nor severe incomplete ischemia (5 and 30 min) caused any measurable breakdown of total or individual fatty acids or phospholipids. Except for a small (and reversible) decrease of inositol plus serine phosphoglycerides in the early postischemic period following 30 min of incomplete ischemia, there were no significant losses of fatty acids or phospholipids during recirculation. Since peroxidation, induced in brain cortical tissue in vitro, characteristically involves degradation of polyenoic fatty acids (arachidonic and docosahexaenoic acids) and of ethanolamine phosphoglycerides, the present in vivo results fail to support the hypothesis that peroxidation of membrane lipids is of primary importance for ischemic brain cell damage. Both complete and severe incomplete ischemia caused a similar increase in the tissue content of free fatty acids (FFA). Thus the FFA pool increased by about 10 times during a 30-min ischemic period, to constitute 1 - 2% of the total fatty acid pool. Since there was a relatively larger increase in polyenoic FFA (especially in arachidonic acid) than in saturated FFA, the release of FFA may be the result of activation of a phospholipase A2 unbalanced by reesterification. Increased levels of FFA persisted during the initial recirculation period, but a gradual normalization occurred and the ischemic changes were essentially reversed at 30 min after restoration of circulation. The pathophysiological implications of the changes in FFA are discussed with respect to mitochondrial dysfunction, formation of cellular edema and prostaglandin-mediated deterioration of postischemic circulation.

Phospholipid degradation and cellular edema induced by free radicals in brain cortical slices.

Abstract: Cellular edema and increased lactate production were induced in rat brain cortical slices by xanthine oxidase and xanthine, in the presence of ferric dialdehyde, was increased 174%. Among the various subcellular fractions of brain cortex, xanthine oxidase-stimulated lipid peroxidation was highest in myelin, mitochondria, and synaptosomes, followed by microsomes and nuclei. Antioxidants, catalase, chlorpromazine, and butylated hydroxytoluene inhibited lipid peroxidation in both homogenates and synaptosomes, indicating H2O2 and radicals were involved. Further, several free fatty acids, especially oleic acid (18:1), arachidonic acid (20:4), and docosahexaenoic acid (22:6) were released from the phospholipid pool concomitant with the degradation of membrane phospholipids in xanthine oxidase-treated synaptosomes. These data suggest that lipases are activated by free radicals and lipid peroxides in the pathogenesis of cellular swelling.

Effect of cellular fatty acid alteration on adriamycin sensitivity in cultured L1210 murine leukemia cells.

Abstract: We have investigated the effect of cellular fatty acid alteration on Adriamycin cytotoxicity using the L1210 lymphoblastic leukemia cell line. Cells growing in Roswell Park Memorial Institute Medium 1640 with 5% fetal bovine serum were modified with respect to fatty acid composition by supplementing their growth medium with 32 microM docosahexaenoic acid (22:6) or oleic acid (18:1). A soft agar clonogenic assay was then used to assess survival following incubation with Adriamycin. When exposed to the drug at a concentration of 0.4 microM, cells grown in the 22:6-supplemented medium were more sensitive (min of drug treatment required to reduce survival by 63% on the exponential portion of the survival curve, 64.9 +/- 4.2 min) to the cytotoxic effects of Adriamycin than cells grown in unsupplemented medium (min of drug treatment required to reduce survival by 63% on the exponential part of the survival curve, 106 +/- 9.7 min) (p less than 0.005). Cytotoxicity of L1210 cells grown in 18:1-supplemented medium was similar to that of cells grown in unsupplemented medium (min of drug treatment required to reduce survival by 63% on the exponential part of the survival curve, 126.6 +/- 9.1 min). The heightened sensitivity to Adriamycin of cells whose medium contained 22:6 increased as the concentration of fatty acid used to supplement the growth medium was increased. The cytotoxicity was also a function of the concentration of Adriamycin from 0.1 to 1.6 microM. When compared to cells grown in unsupplemented medium, those grown in 22:6-supplemented medium contained 3- to 4-fold more polyunsaturated fatty acids in their phospholipids, with a resultant doubling in the mean number of double bonds per fatty acid molecule. These data demonstrate that modification of cellular fatty acid composition may dramatically affect the sensitivity of a tumor cell to Adriamycin.

Choline Uptake in Cultured Human Y79 Retinoblastoma Cells: Effect of Polyunsaturated Fatty Acid Compositional Modifications

Abstract: Choline uptake in Y79 human retinoblastoma cells occurs through two kinetically distinguishable processes. The high-affinity system shows little sodium or energy dependence, and it does not appear to be linked to acetyl CoA; choline O-acetyltransferase. When the cells are grown in a culture medium containing 10% fetal bovine serum, the high-affinity system has a K'm= 2.16 +/- 0.13 microM and V'max = 27.0 +/- 2.9 pmol min-1 mg-1, whereas the low-affinity system has a k'm = 20.4 +/- 1.3 microM and V'max = 402 +/- 49 pmol min-1 mg-1. Under these conditions, the polyunsaturated fatty acid content of the cell membranes is relatively low. When the polyunsaturated fatty acid content of the microsomal membrane fraction was increased by supplementing the culture medium with linolenic or docosahexaenoic acids (n-3 polyunsaturated fatty acids) or arachidonic acid (n-6 polyunsaturated fatty acid), the K'm of the high-affinity choline transport system was reduced by 40--60%. The V'max also was reduced by 20--40%. Supplementation with oleic acid, the most prevalent monounsaturated fatty acid, did not affect either kinetic parameter. The results suggest that one functional effect of the high unsaturated fatty acid content of neural cell membranes is to facilitate the capacity of the high-affinity choline uptake system to transport low concentrations of choline. This effect appears to be specific for polyunsaturated fatty acids but not for a single type, for it is produced by members of both the n-3 and n-6 classes of polyunsaturated fatty acids.

Inclusion compound of eicosapentaenoic acid or docosahexaenoic acid with cyclodextrin

Abstract: This disclosure describes an inclusion compound of cyclodextrin in which at least one guest compound selected from the group of eicosapentaenoic acid, docosahexaenoic acid and alkali metal salts and alkyl esters thereof is included.

Incorporation and turnover of essential fatty acids in phospholipids and neutral lipids of rainbow trout

Abstract: 1. 1. The turnover of rainbow trout (Salmo gairdneri) lipid was monitored in fish receiving essential fatty acid (EFA) replete and EFA deficient diets using [1-14C]-linolenic acid (C18:3ω3). 2. 2. Forty percent of administered radioactivity was recovered in total lipid after 7 days. 3. 3. Eighty-five percent of incorporated label was recovered in C18:3ω3 derivatives, primarily docosahexaenoic acid (22:6ω3). 4. 4. Over 10 weeks, 14C activity in neutral lipid (NL) remained constant whereas that in phospholipid (PL) declined due to loss of label from shorter chain ω3 fatty acids. The mass and specific activity of longer chain ω3 fatty acids remained constant. 5. 5. There was an accumulation of 14C activity and C22:6ω3 in PE at the expense of PC. 6. 6. The pattern of incorporation of 32P inorganic phosphate into molecular classes of phosphatidylcholine (PC) of EFA deficient fish indicated that the rate of turnover of docosahexaenoyl PC was not diminished by EFA deficiency. 7. 7. It is hypothesized that retention of C22:6ω3 in EFA deficiency is due to the presence of an efficient recycling system during membrane turnover.

The lipid composition of human liver microsomes.

Abstract: The lipid composition of human liver microsomes isolated from liver biopsy samples obtained at abdominal surgery has been determined. Human liver microsomal phospholipid is composed of 49% phosphatidylcholine, 31% phosphatidylethanolamine, 14% phosphatidylserine+phosphatidylinositol and 6% sphingomyelin, very similar to the phospholipid composition of rat liver microsomes. The fatty acid composition of human liver microsomes is remarkable only for its content of polyunsaturated fatty acids, with 20% of the fatty acids consisting of arachidonic, docosatetraenoic, docosapentaenoic and docosahexaenoic acids. This value contrasts with 33% in rats and 9% in rabbits. The molar cholesterol/phospholipid ratio in human liver microsomes is 0.069, similar to the ratio in rat and rabbit microsomes.

Effect of linoleic acid-rich diet on blood pressure, lipids, catecholamines, and dopamine -beta-hydroxylase in spontaneously hypertensive rats.

Abstract: Spontaneously hypertensive rats (SHR) and normotensive Wistar rats were fed a linoleic acid-rich (LAR) and -deficient (LAD) diet for 22 weeks, respectively. Although linoleic acid (LA) and arachidonic acid (AA) in serum and liver triglycerides markedly increased after a LAR diet, LA was significantly lower and AA was higher in SHR when compared to normotensive control rats. Thus, the percentage of both fatty acids remained different like in animals fed a commercial diet. On the contrary, in SHR and normotensive rats fed a LAD diet no differences in the LA and AA content could be found between the groups. In these rats, however, n-3 fatty acids (eicosapentaenoic and docosahexaenoic acids) in serum triglycerides were increased. Blood pressure, serum triglycerides and total cholesterol appeared unchanged, whereas HDL-cholesterol was increased after a LAR diet. Dopamine, adrenaline and noradrenaline content as well as dopamine-beta-hydroxylase activity were augmented in adrenal glands of SHR fed a LAR diet. In spite of distinct biochemical alterations the genetically determined hypertension in rats could not be influenced by a long-lasting diet containing a high amount of LA which has been proved to be effective on lowering blood pressure in other hypertensive rat models.

Use of phospholipase A to compare phospholipid organization in synaptic membranes, myelin, and liposomes.

Abstract: The pattern of fatty acid release from rat synaptic membranes in the presence of phospholipase A2 (Vipera russelli) was compared to that from liposomes comprised of phospholipids. Phospholipase A2 more readily attacked myelin and synaptic membranes than liposomes prepared from total phospholipids derived from myelin. Although hydrolysis of liposomal phospholipids occurred in the absence of added calcium, the presence of 2mm CaCl2 or 2% bovine serum albumin significantly enhanced the phospholipase attack of liposomes, but not synaptic membranes or myelin. Phospholipase exhibited a marked preference for phospholipids containing docosahexaenoic acid (22∶6) in the synaptic membranes, while with liposomes the pattern of released fatty acid reflected the fatty acid composition in the two-position of the phospholipids. Although either calcium or albumin markedly increased the phospholipase hydrolysis of liposomes, neither affected the hydrolysis of synaptic membranes or the pattern of fatty acid release from liposomes. It was concluded that the nonlipid constituents, particularly the proteins, of biomembranes were responsible for the organization of the phospholipids and accounted for the observed differences between liposomes and synaptic membranes with respect to enzymic accessibility.

Effect of chloroquine treatment on the different phospholipid species of rat liver lysosomes.

Abstract: The lysosomal phospholipids of rat liver were determined after treatment of the animals with chloroquine for varying periods up to 15 days. During this period, all the measured phospholipids increased. After two weeks of treatment the absolute level of each phospholipid had increased 3 to 6-fold, with the exception of bis(monoacylglycero)phosphate which was increased 25-fold, accounting for one third of the total phospholipids. The fatty acid pattern not only differed between the classes of lipids; it changed during treatment within every lipid class. In addition to other changes, the polyenoic fatty acids of the main glycerophospholipids were markedly reduced between the 3rd and 14th day of chloroquine treatment: to one half in phosphatidylcholine, to about one tenth in phosphatidylethanolamine, and to one quarter in phosphatidylinositol. However, the polyenoic fatty acid content of bis(monoacylglycero)phosphate was doubled, reaching 76% of the total at the end of treatment. Whereas docosahexaenoic acid was not detected in this acidic phospholipid in the first 3 days of treatment, it was present to the extent of 55% of the total fatty acids after 15 days of chloroquine application;

Long-chain fatty acids bound to α-fetoprotein and to serum albumin from fetal and adult pig

Abstract: 1. Pig alpha-fetoprotein (AFP) and albumin were isolated from fetal serum by DEAE-Sephadex ion exchange chromatography combined with Cibacron Blue-Sepharose and trypsin-Sepharose adsorptions. 2. AFP, fetal albumin and adult albumin carried 2.6, 2.4, and 1.9 moles of fatty acids per mole of protein, respectively. 3. Most of fatty acids bound to AFP were polyunsaturated: mainly arachidonic (20:4, n-6) and docosahexaenoic (22:6, n-3) acids, which accounted respectively for 21.7 and 18.8% of the total fatty acids. 4. By contrast, the fatty acids found in the albumins (fetal and adult) were preferentially saturated and monounsaturated. 5. Arachidonic acid was a minor component in both albumins, and no docosahexaenoic acid was detected.

The fatty acid levels of rat alpha-fetoprotein derived from fetuses, pregnancy and hepatoma sera.

Abstract: The fatty acid levels of alpha-fetoprotein (AFP) isolated from term rat fetuses is about half that of similar human preparations. Arachidonic and docosahexaenoic acids constitute about 33% of the total fatty acids in the rat AFP isolates. The AFP isolated from rat maternal and hepatoma sera have relatively low levels of these fatty acids. A comparison of the fatty acid contents of selected tissues from pregnant and non-pregnant rats does not show differences which might reflect the variable fatty acid levels of the fetal and maternal source AFP preparations.

Food containing highly unsaturated fatty acid

Abstract: PURPOSE: To provide the titled food having the characteristic properties (taste, smell, feeling to the teeth, color, etc.) of the original food, and takable continuously without unagreeable feeling, by coating an oil or fat containing highly unsaturated fatty acid with an edible coating film, and adding the coated oil, etc. to a food. CONSTITUTION: The oil or fat 1 containing a highly unsaturated fatty acid having a carbon number of about ≥18 and a unsaturated bond number of about ≥4 [e.g. eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), etc.] in an amount of ≥5wt% based on whole fatty acids, is coated with an edible film- forming substance (e.g. gelatin, casein, alginic acid, etc.) to form an coated oil or fat 10 having edible coating film 2. The oil or fat is preferably formed in granular form having a diameter of about ≤1W2mm. The coated oil or fat 10 is added to a food 3 such as biscuit, bread, custard cream, etc. COPYRIGHT: (C)1984,JPO&Japio

Preparation of antitumor complex

Abstract: PURPOSE: To prepare the titled novel complex having remarkably reduced toxicity and improved target effect to the tumor tissue, and useful as an antitumor agent, by reacting an antitumor compound with a specific unsaturated fatty acid or its reactive derivative. CONSTITUTION: A compound having antitumor activity [e.g. aminoglycoside antitumor compound (e.g. daunorubicin, toxorubicin, etc.)] is made to react with a 10W30C unsaturated fatty acid (e.g. arachidonic acid, docosahexaenoic acid, etc.) or its reactive derivative (e.g. acid halide) to obtain the novel antitumor complex. The reaction is carried out usually in a solvent (e.g. DMF) in the presence of a condensation agent (e.g. water-soluble carbodiimide) at 4W5pH and 10W30°C for 2W8hr. The ratio of the antitumor compound to the fatty acid in the complex depends upon the number of the reactive groups in the antitumor compound; for example, daunorubicin and toxorubicin having one amino group forms an amide bond with 1mol of the fatty acid. COPYRIGHT: (C)1984,JPO&Japio

Method for concentrating and separating eicosapentaenoic acid and docosahexaenoic acid

Abstract: PURPOSE: To concentrate and separate the titled fatty acids safely with a high efficiency, by hydrolyzing a fat or oil containing the titled fatty acids in a solution of an alkali metallic hydroxide in ethanol, and cooling the hydrolytic product to deposit alkali metallic salts of saturated fatty acids CONSTITUTION: A fat or oil containing eicosapentaenoic acid (EPA) and /or docosahexaenoic acid (DHA) is hydrolyzed in a solution of an alkai metallic hydroxide in ethanol, preferably containing 20% or less, particularly 10% or less, water, under heating, and the resultant saponified solution is directly cooled to 5W25°C to deposit alkali metallic salts of unnecessary saturated fatty acids as crystals, which are then removed by the filtration Water is then added to the resultant filterate, and the mixture is acidified with a mineral acid and extracted with an organic solvent slightly soluble in water and washed with water The solvent is then distilled away to give the aimed concentrated oil of EPA and/or DHA A fat or oil containing 10W30wt% total of EPA and DHA is preferably used as the raw material fat or oil COPYRIGHT: (C)1984,JPO&Japio