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PubMed1995

[Effect of free fatty acid on cholesterol nucleation in model bile].

We studied the effect of free fatty acids on cholesterol nucleation in model bile with a sensitive cholesterol crystal growth assay. Palmitic acid, oleic acid, linoleic acid and arachidonic acid were added to model biles in increasing concentrations from 0.5 to 20 umol/ml. The nucleation time of model bile with free fatty acids decreased to 30%-50% of control bile. The final crystal concentration increased with higher concentrations of palmitic acid. However, we found a decrease in the final crystal concentration with the unsaturated fatty acid-soleic acid, linoleic acid and arachidonic acid. The increase in the maximum crystal growth rate was marked in the model biles as linoleic acid was added. These findings show the effect of non-protein fraction in biles on gallstone formation and support the view that free fatty acids are pro-nucleating factors.

Bile↗

PubMed1994

Antithetic relationship of dietary arachidonic acid and eicosapentaenoic acid on eicosanoid production in vivo.

Eicosanoids are oxidative derivatives of arachidonic acid. When produced in excessive amounts, many are proinflammatory and/or prothrombotic agents. N-3 polyunsaturated fatty acids (PUFA) have been used to attenuate tissue arachidonic acid (AA, 20:4 n-6) levels and thus modulate eicosanoid production. However, there is growing evidence that dietary arachidonic acid may also be able to modulate eicosanoid formation by enriching tissue phospholipids with AA. Therefore, the effects of dietary AA and n-3 PUFA are in diametric opposition. This study investigates the antithetic relationship of dietary AA and eicosapentaenoic acid (EPA, 20:5 n-3) on fatty acid composition of hepatic phospholipids and eicosanoid production in vivo. Forty-nine CD-1 male mice were randomly divided into four dietary groups. Identical diets were supplemented with ethyl esters (1.5% w/w) of the following fatty acids: oleic acid (OA, 18:1 n-9), AA, EPA or AA+EPA. After 4 weeks on diet, peritoneal cells were stimulated in vivo with opsonized zymosan and the peritoneal exudates were analyzed for eicosanoid production (PGE2, 6-keto-PGF1 alpha, TXB2, LTB4, LTE4, and LTE5). Hepatic phospholipids were enriched with AA when AA was included in the diet, and EPA was enriched at the expense of AA when EPA was added to the diet. However, when AA was added to the diet containing equivalent amounts of EPA (AA+EPA), any effect EPA had on modulating hepatic phospholipid fatty acid composition was almost completely eliminated. Similar effects were observed with eicosanoid production. The pooled eicosanoid production in the AA group was 41% and 300% higher compared to the OA (control) and EPA groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

[A gas chromatographic analysis of the fatty acid composition of Yersinia pestis].

The fatty acid composition of Y. pestis strains, the causative agent of plaque, has been studied. Y. pestis cells have been found to contain great amounts of palmitoleic acid, methylenehexadecanoic acid, oleic acid with elaidic acid, palmitic acid and pentadecanoic acid. Lauric acid, myristic acid, 3-oxymyristic acid and methyleneoctadecanoic acid have been detected in moderate amounts. Vaccine strains, virulent museum and newly isolated strains, while differing in their antigenic structure, have proved to be uniform in their fatty acid composition. In Y. pestis cels, grown on a solid medium for a longer period and at higher temperature, an increased proportion of saturated acids is observed.

Chromatography, Gas↗

PubMed1993

A systematic analytical chemistry/cell assay approach to isolate activators of orphan nuclear receptors from biological extracts: characterization of peroxisome proliferator-activated receptor activators in plasma.

Using a novel combination of analytical chemical and molecular biological techniques, lipophilic components of human plasma separated according to their physico-chemical properties were screened for their ability to activate the rat peroxisome proliferator-activated receptor (rPPAR). Activation of an rPPAR/glucocorticoid receptor chimera stably expressed in CHO cells by fractions in the initial screening guided further subfractionation. Characterization of an active subfraction by gas chromatography alone and in combination with mass spectrometry (GC-MS), indicated the presence of free fatty acids. Individual active components in this mixture were isolated by a final fractionation using high performance liquid chromatography (HPLC). GC-MS analyses of HPLC fractions able to activate the chimeric receptor identified palmitic acid, oleic acid, linoleic acid, and arachidonic acid as endogenous activators of rPPAR. No other activators were identified. This approach is able to specifically extract and identify endogenous activators of PPAR from a complex biological extract and as such may be valuable in the identification of activators of other orphan receptors in the steroid hormone receptor superfamily.

Chemical Fractionation↗

PubMed1995

[Free fatty acids in gallbladder bile].

Using gas chromatography and high performance liquid chromatography (HILC), we examined free fatty acid and lecithin molecular species in gallbladder biles from patients with cholesterol gallstones. Effect of free fatty acids on cholesterol nucleation in model bile was studied by a sensitive cholesterol crystal growth assay. Compared to bile of controls, biles from patients with gallstones had higher total free fatty acid level, more palmitic acid, more stearic acid, more linoleic acid and arachidonic acid. The lecithin pattern was similar in all. After free fatty acids were added to model bile, palmitic acid, oleic, acid, linoleic acid and arachidonic acid had significant effect of pro-nucleating, free fatty acids on non-protein pro-nucleating factor. These data suggest that variations in quantitation and composition of free fatty acids are importanct in the pathogenesis of cholesterol gallstone formation.

Bile↗

PubMed1998

Cytotoxicity and apoptosis produced by arachidonic acid in HepG2 cells overexpressing human cytochrome P-4502E1.

The goal of the current study was to evaluate the effects of arachidonic acid, as a representative polyunsaturated fatty acid, on the viability of a HepG2 cell line, which has been transduced to express human cytochrome P4502E1 (CYP2E1). Arachidonic acid produced a concentration- and time-dependent toxicity to HepG2-MV2E1-9 cells, which express CYP2E1, but little or no toxicity was found with control cells. In contrast to arachidonic acid, oleic acid was not toxic to the HepG2-MV2E1-9 cells. The cytotoxicity of arachidonic acid involved a lipid peroxidation type of mechanism since toxicity was enhanced after depletion of cellular glutathione; formation of malondialdehyde and 4-hydroxy-2-nonenal was markedly elevated in the cells expressing CYP2E1, and toxicity was prevented by antioxidants and the iron chelator desferrioxamine. The CYP2E1-dependent arachidonic acid toxicity appeared to involve apoptosis, as demonstrated by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling and DNA laddering experiments. Trolox, which prevented toxicity of arachidonic acid, also prevented the apoptosis. Transfection with a plasmid containing bcl-2 resulted in complete protection against the CYP2E1-dependent arachidonic acid toxicity. It is proposed that elevated production of reactive oxygen intermediates by cells expressing CYP2E1 can cause lipid peroxidation, which subsequently promotes apoptosis and cell toxicity when the cells are enriched with polyunsaturated fatty acids such as arachidonic acid.

Animals↗

PubMed1998

[Factors aggravating bronchial asthma in urban children (II)--The involvement of atopy and serum fatty acids, and their interaction with urban living environment].

The aggravation of bronchial asthma in today's urban child population was studied by an epidemiological study in order to elucidate the involvement of food habits as well as individual factors such as age, sex, and history of atopic dermatitis, and the interaction with urban living environments. The asthma group consisted of 202 children under 12 years old who had been recently diagnosed as having bronchial asthma and under the care of Osaka Prefectural Habikino Hospital. The non-asthma group consisted of 81 children under 12 years old who had been under care at Osaka Prefectural Hospital but had no present history of allergic symptom. The individual factors and the urban living environments (atmospheric environment, housing style) were surveyed by questionnaire. Also, the mite (Dp: Dermatophagoides pteronyssinus, Df: Dermatophagoides farinae) specific immunoglobulin E (Dp-IgE, Df-IgE) and the composition of serum fatty acid were examined as objective indicators for atopy and dietary habits, respectively. In this study, bronchial asthma was classified into two types: atopic/non-atopic, according to whether Dp-IgE was present/absent (positive/negative). Thus, for the risk factors given above, their involvement in each type of asthma was examined. As atopy is an important factor of child asthma, the relative risk (odds ratio) of Dp-IgE increase (atopy) was also examined by logistic regression analysis in each of the asthma and non-asthma groups. The results are as follows: 1. As age increased, the risk of atopy increased but the risk of asthma decreased. 2. The risk of asthma increased as Dp-IgE rather than Df-IgE increased. 3. For the composition of serum fatty acid, the lower quartile ranking (LQR) group for a saturated fatty acid, stearic acid, and the upper quartile ranking (UQR) group for a mono-unsaturated fatty acid, oleic acid, had a higher risk of nonatopic asthma. 4. The LQR group for omega 6-poly-unsaturated fatty acid such as linoleic acid, had a lower risk of atopy. 5. The UQR group for a omega 3-poly-unsaturated fatty acid, eicosapentaenoic acid, had a higher risk of nonatopic asthma. The UQR of eicosapentaenoic acid and living environments within 25 m from a major road or housing of reinforced concrete structure showed involvement in synergistic increase in the risk of non-atopic asthma.

Asthma↗

PubMed2002

Biosynthesis of triacylglycerol molecular species in an oleaginous fungus, Mortierella ramanniana var. angulispora.

The incorporation of radiolabeled lipid precursors into triacylglycerol (TG) molecular species in Mortierella ramanniana var. angulispora, an oleaginous fungus, was studied to determine the biosynthetic pathways for TG molecular species. Radiolabeled TG molecular species were separated and quantified by reverse-phase high performance liquid chromatography with a radioisotope detector. The major TG molecular species labeled by [1-(14)C]oleic acid at 30 degrees C were OOP, OOO, and OPP (TG molecular species designations represent three constituent acyl groups. G, gamma-linolenic acid; L, linoleic acid; O, oleic acid; S, stearic acid; P, palmitic acid), which were abundant TG molecular species in this fungus. The incorporation of [1-(14)C]oleic acid at 15 degrees C into these molecular species was the same, while that into most other species was decreased, suggesting that biosynthesis of major molecular species such as OOP, OOO, and OPP differs from that of other TG molecular species. [1-(14)C]Linoleic acid incorporation indicated that the major labeled molecular species were LOP and LOO, which may be due to acylation of oleoyl, palmitoyl-glycerol, or dioleoyl-glycerol by exogenous linoleic acid. This is basically the same mechanism as for OOP and OOO biosynthesis from exogenous oleic acid. [(14)C(U)]Glycerol incorporation suggested that TG molecular species containing palmitic acid such as OPP were more readily synthesized through the de novo pathway. Further experiments involving inhibitors such as sodium azide and cerulenin suggested that OOO biosynthesis included a mechanism differing from that in the cases of OOP and OPP. Trifluoperazine, which inhibits the conversion from phosphatidic acid to TG, decreased [1-(14)C]oleic acid incorporation into all molecular species, suggesting that the incorporation into all molecular species included the de novo TG biosynthetic pathway via phosphatidic acid. These results revealed that the biosynthetic pathways for TG molecular species can be classified into several groups, which exhibit different sensitivities to low temperature and inhibitors of lipid metabolism. This implies that the composition of TG molecular species is regulated through different biosynthetic pathways responsible for specific TG molecular species, providing a new insight into the biosynthesis of TG molecular species.

Carbon Radioisotopes↗

PubMedDate not supplied

Microbial production of hydroxy and oxo fatty acids by several microorganisms as a model of adipocere formation.

Some varieties of aerobic or anaerobic microorganisms from the human stool and adipocere were separated and identified. These separated microorganisms together with other authentic ones produced 10-hydroxystearic acid from oleic acid. Some bacteria could convert oleic acid to 10-oxostearic acid as well as 10-hydroxystearic acid. These findings indicate that the microbial enzyme(s) catalyzes the hydration of oleic acid and probably the oxidation of this hydrated product. Aerobic bacteria as well as anaerobic microorganisms were found to be involved in the formation of adipocere.

Bacillus subtilis↗

PubMed1992

Effect of free fatty acids on GABAA receptor ligand binding.

Phospholipase A2 (PLA2) treatment of synaptosomal membranes, which causes the release of fatty acids, particularly unsaturated fatty acids, inhibits the flux of chloride ions through the gamma-aminobutyric acid (GABA) benzodiazepine receptor ion channel in response to activation by agonists. PLA2 treatment has also been shown to affect ligand binding to the receptor. In the present study, we have investigated the effect of unsaturated free fatty acids, arachidonic acid and oleic acid and saturated free fatty acids, arachidic acid and stearic acid on various characteristics of GABAA receptor ligand binding. Only the unsaturated fatty acids showed any effect: arachidonic acid and oleic acid enhanced flunitrazepam binding and muscimol binding but inhibited tert-butylbicyclophosphorothionate (TBPS) binding in a dose-dependent manner. The effects on muscimol and TBPS binding were shown to be due to changes in receptor density by saturation analysis. Oleic acid and arachidonic acid also decreased the enhancement of flunitrazepam and muscimol binding by cartazolate and pentobarbital but did not affect GABA enhancement of flunitrazepam binding. These data indicate that unsaturated free fatty acids can mimic the effects of PLA2 treatment and underline the importance of the lipid microenvironment on ligand binding to the GABAA receptor.

Animals↗

PubMed2001

X-ray diffraction and spectroscopic studies of oleic acid-sodium oleate.

The sodium oleate-oleic acid (1:1) complex (NaHOl(2)) is characterized using X-ray diffraction, FT-IR photoacoustic spectroscopy, FT-Raman spectroscopy, and DSC. The special arrangement of hydrogen-bonded pairs of carboxylic acid and carboxylate groups into unique "head-group" is supported by frequency shifts and partial or total disappearance of characteristic vibrations of carboxylic acid dimer and of carboxylate groups. The well-ordered state of hydrocarbon chains is demonstrated by the existence of sharp Raman bands in the C-C stretching region (1000-1150 cm-1) and other conformationally sensitive modes. The FT-Raman results suggest that the transition at about 32 degrees C involves the cooperative melting of methyl- and carboxyl/carboxylate-sided hydrocarbon chains. From the X-ray diffraction data it is clear that this transition is associated with the disintegration of the hydrogen-bonded carboxylate-carboxylic acid complex, followed by the separate formation of oleic acid and sodium oleate. The packing of hydrocarbon chain in the acid-soap complex is different from the parent oleic acid or sodium oleate. The hydrocarbon chains in the NaHOl(2) form more stable packing (O subcell) in comparison to that of oleic acid. A temperature composition phase diagram is presented.

Calorimetry, Differential Scanning↗

PubMed1987

Uncoupling of oxidative phosphorylation. 1. Protonophoric effects account only partially for uncoupling.

The mechanism of uncoupling of oxidative phosphorylation by carbonyl cyanide p-trifluoromethoxy)phenylhydrazone (FCCP), a typical weak acid protonophore, oleic acid, a fatty acid, and chloroform, a general anesthetic, has been investigated by measuring in mitochondria their effect on (i) the transmembrane proton electrochemical potential gradient (delta mu H) and the rates of electron transfer and adenosine 5'-triphosphate (ATP) hydrolysis in static head, (ii) delta mu H and the rates of electron transfer and ATP synthesis in state 3, and (iii) the membrane proton conductance. Both FCCP and oleic acid increase the membrane proton conductance, and accordingly, they cause a depression of delta mu H [generated by either the redox proton pumps or the adenosinetriphosphatase (ATPase) proton pumps]. Although their effects on ATP synthesis/hydrolysis, respiration, and delta mu H are qualitatively consistent with a pure protonophoric uncoupling mechanism and an additional inhibitory action of oleic acid on both the ATPases and the electron-transfer enzymes, a quantitative comparison between the dissipative proton influx and the rate of either electron transfer or ATP hydrolysis (multiplied by either the H+/e- or the H+/ATP stoichiometry, respectively) at the same delta mu H shows that the increase in membrane conductance induced by FCCP and oleic acid accounts for the stimulation of the rate of ATP hydrolysis but not for that of the rate of electron transfer. Chloroform (at concentrations that fully inhibit ATP synthesis) only very slightly increases the proton conductance of the mitochondrial membrane and causes only a little depression of delta mu H.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1986

The role of thyroxine (T4)-binding serum proteins in oleic acid-induced increase in free T4 in nonthyroidal illnesses.

We studied the effects of various concentrations of oleic acid (0.1-3.3 mM), such as are often found in the serum of patients with nonthyroidal illness, on the dialyzable (free) fraction of T4 (DFT4) in three types of serum samples: pooled normal serum (PNS), pooled pregnancy serum (PPS), and pooled serum of hospitalized patients (PSHP). The samples were extracted with diethyl ether to remove endogenous fatty acids before being tested in the DFT4 assay. Oleic acid caused only a moderate increase in DFT4 in PNS; a significant (greater than 2 SD above control) increase (15%) was found with 2.0 mM oleic acid, and the maximal dose of oleic acid (3.3 mM) caused a 33% increase in DFT4. However, the DFT4-increasing effect of oleic acid was enhanced (increase in DFT4 of 33% caused by 0.9-1.2 mM oleic acid) when the serum tested had low (0.5 times normal) albumin and prealbumin concentrations with either normal (50% PPS) or half-normal TBG (50% PNS). The effect of oleic acid in 100% PSHP was significantly (P less than 0.005) greater than that in 100% PNS, and it was close to that in 50% PNS (increase in DFT4 with 3.3 mM oleic acid, 118% in PSHP vs. 98% in 50% PNS). Normalization of serum albumin in PSHP by adding exogenous albumin markedly reduced the DFT4-increasing effect of oleic acid; the maximal increase in DFT4 of 64% with 3.3 mM oleic acid in albumin-normalized PSHP was equalled with 1.3 mM oleic acid in unmodified PSHP. The data suggest that the serum concentrations of albumin and other T4-binding proteins are important in modulating the DFT4-increasing effect of oleic acid and that oleic acid may contribute to the reduced serum binding of T4 in nonthyroidal illness.

Dialysis↗

PubMed1990

Inhibitors directed to binding domains in neutrophil elastase.

Human neutrophil elastase (HNE) can be inhibited by unsaturated fatty acids, including oleic acid [Ashe, B. M., & Zimmerman, M. (1977) Biochem. Biophys. Res. Commun. 75, 194-199; Cook, L., & Ternai, B. (1988) Biol. Chem. Hoppe-Seyler 369, 627-631], but is not affected by saturated fatty acids. We have shown that the interaction of oleic acid with HNE can be characterized by two apparent inhibitory modes: a high-affinity mode (Ki = 48 +/- 3 nM), resulting in partial noncompetitive inhibition (87% residual activity), and a competitive inhibitory mode of lower affinity (Ki = 16 +/- 1 microM). Binding of oleate in the high-affinity mode induces a blue shift in the endogenous fluorescence arising from the tryptophan residues in HNE. This shift is maximal in the presence of 1 microM oleate; higher concentrations of fatty acid have no further effect on the fluorescence spectrum. The negatively charged fluorescent ester of oleic acid and hydroxypyrenetrisulfonate (HPTSoleate) interacts with HNE at an apparent single site (Ki = 44 +/- 3 nM), resulting in competitive inhibition. A blue shift in the emission maximum of the pyrene fluorescence at 410 nm and a decrease in the ratio of the intensities of the maximum at 388 and 410 nm indicate that upon binding to HNE the environment of the pyrene ring in HPTSoleate becomes more hydrophobic.(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine↗

PubMed1985

Effect of exogenous glucagon and free fatty acids on gluconeogenesis in fasting neonatal pigs.

Thirty-two pigs (1 d old) were used to determine if exogenous glucagon and(or) free fatty acids (FFA oleic acid) would enhance gluconeogenesis and glucose homeostasis during fasting. Pigs were acquired at birth, fitted with an indwelling arterial cannula (via umbilicus) and fasted 24 h to deplete liver glycogen. A jugular cannula was inserted nonsurgically 8 to 10 h before initiation of a primed-continuous infusion consisting of control (excipient), glucagon (Glu), oleic acid (FFA), or both glucagon and oleic acid (Glu-FFA). Plasma Glu averaged 395 pg/ml preinfusion and was similar across treatments. The concentration increased fivefold (P less than .05) by 80 min for Glu and Glu-FFA pigs and remained constant thereafter (160 min: 2,379, 2,258 pg/ml; 240 min: 2,355, 2,274 pg/ml, respectively). Glucagon infusion did not alter plasma glucose after 240 min of infusion (control, 50 vs Glu, 51 mg/dl); however, Glu-FFA effected an increase (60 mg/dl, P less than .10). In contrast, pigs infused with FFA alone had a lower glucose concentration (40 mg/dl, P less than .10). Rate of glucose synthesis was determined using liver slices, acquired immediately postinfusion, with alanine and lactate as substrate (7.5 mM). The rate of synthesis was not altered by Glu or Glu-FFA infusion (2.91, 2.43 mumol glucose X g-1 X h-1 vs 2.91 for control). In contrast, exogenous FFA reduced synthesis to 1.85 mumol glucose X g-1 X h-1 (P less than .05) with lactate as substrate. It appears that Glu is not the primary factor limiting gluconeogenesis in fasting newborn pigs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Effects of eicosapentaenoic acid and arachidonic acid on incorporation and metabolism of radioactive linoleic acid in cultured human fibroblasts.

Effects of exogenous eicosapentaenoic acid, arachidonic acid and oleic acid on incorporation and metabolism of [14C] linoleic acid were examined in cultured human fibroblasts obtained from three donors of different ages. Eicosapentaenoic acid treatment (40 microM) inhibited incorporation of radioactive linoleic acid and actively reduced radioactivity of desaturation-elongation metabolites in phospholipids, predominantly in the phosphatidylethanolamine fraction. In contrast, radioactivities of the metabolites in triacylglycerols were significantly increased with arachidonic acid treatment (40 microM): eicosapentaenoic acid had a smaller effect or none. Oleic acid had virtually no effect. These effects were consistent in the three cell lines, but responses to treatment with the acids differed considerably among individual cells. The pool of linoleic acid metabolites in triacylglycerols may not be negligible. The exogenous fatty acids may influence both the transfer of lipids between the major lipid pools as well as the activities of the desaturation-elongation system.

Arachidonic Acid↗

PubMed2000

Dietary unsaturated fatty acids in type 2 diabetes: higher levels of postprandial lipoprotein on a linoleic acid-rich sunflower oil diet compared with an oleic acid-rich olive oil diet.

OBJECTIVE: The present study was undertaken to examine the effect of a polyunsaturated fat diet compared with an isocaloric Mediterranean-style monounsaturated fat diet. RESEARCH DESIGN AND METHODS: This was a randomized 2-week crossover study on either a high-polyunsaturated or a high-monounsaturated fat diet in 11 well-controlled diabetic men. Blood was taken fasting and for up to 8 h after a high fat meal. Lipoproteins were isolated by sequential ultracentrifugation. Apolipoprotein (apo) B48 and apo B100 were separated by PAGE. Fatty acids were analyzed by gas-liquid chromatography RESULTS: Fasting blood glucose and insulin levels were significantly higher on the linoleic acid diet compared with the oleic acid diet (P < 0.01 and P < 0.002, respectively). Plasma cholesterol and LDL cholesterol levels were also significantly higher on the linoleic acid diet (P < 0.001). Likewise, fasting chylomicron apo B48 and apo B100 (P < 0.05) and postprandial chylomicron and VLDL apo B48 and B100 (P < 0.05) were also higher on the linoleic acid diet. CONCLUSIONS: This study suggests that, in type 2 diabetes, an oleic acid-rich Mediterranean-type diet versus a linoleic acid-enriched diet may reduce the risk of atherosclerosis by decreasing the number of chylomicron remnant particles.

Apolipoprotein B-48↗

PubMed1998

Anticonvulsant effect of polyunsaturated fatty acids in rats, using the cortical stimulation model.

Recent studies have shown that long-chain polyunsaturated fatty acids can prevent cardiac arrhythmias, attributed to the reduction in excitability of cardiomyocytes, owing mainly to a shift in hyperpolarizing direction of the inactivation curves of both Na+ and Ca2+ currents and to a slowed recovery from inactivation. Qualitatively similar effects of polyunsaturated fatty acids on inactivation parameters have been observed in freshly isolated hippocampal neurons. Since the same effects are presumed to underlie the action of some established anticonvulsant drugs, polyunsaturated fatty acids might have an anticonvulsant action as well. We have investigated this for eicosapentaenoic acid, docosahexaenoic acid, linoleic acid and oleic acid, employing cortical stimulation in rats, a seizure model allowing the determination of the full anticonvulsant effect-time profile in freely moving, individual animals. I.v. infusion of 40 micromol of eicosapentaenoic acid or docosahexaenoic acid over a period of 30 min, modestly increased the threshold for localized seizure activity after 6 h by 73 +/- 13 microA (mean +/- S.E.M.; n = 7) and 77 +/- 17 microA (n = 7), respectively, and the threshold for generalized seizure activity by 125 +/- 20 and 130 +/- 19 microA, respectively (P < 0.001). The thresholds remained elevated for 6 h after infusion, but returned to baseline the next day. Free plasma concentrations in rats treated with eicosapentaenoic acid or docosahexaenoic acid, averaged 5.7 +/- 1.6 microM (n = 4) for eicosapentaenoic acid and 12.9 +/- 1.8 microM (n = 5) for docosahexaenoic acid at the end of infusion, but declined to undetectable levels within 3 h. Linoleic acid and oleic acid were less effective. Possible mechanisms for the modest anticonvulsant effect but of long duration with the polyunsaturated fatty acids are discussed.

Animals↗