Biomedical subjects

M Lagarde

Publications and source records attributed to M Lagarde.

At least 19 recordsLinked to original sources

PubMed1992

Lower levels of lipid peroxidation in human platelets incubated with eicosapentaenoic acid.

The modulatory effects of eicosapentaenoic acid (EPA) on platelet arachidonic acid (AA) metabolism were applied to an in vitro model of oxidant stress. Unstimulated normal human blood platelets were first treated with a thiol-oxidizing agent, azodicarboxylic acid bis(dimethylamide) (diamide) (1 microM), and then incubated with a low concentration of EPA (100 nM). Diamide treatment led to a lower alpha-tocopherol content compared to control. Formation of MDA, a marker of the overall lipid peroxidation, as well as formation of 12-hydroxyeicosatetraenoic acid (12-HETE), the 12-lipoxygenase end-product of AA, were both higher in diamide-treated platelets. Subsequent incubation of diamide-treated platelets with EPA counteracted the effects of oxidant stress induced pharmacologically by diamide. Interestingly, EPA prevented the alpha-tocopherol level from falling and the overall lipid peroxidation from increasing as it did during diamide treatment. In particular, incubation of diamide-treated platelets with EPA led to significantly lower amounts of 12-HETE. Conversely, preincubation of platelets with 100 nM EPA protected cells from oxidizing effects induced by diamide treatment, either on the level of lipid peroxides or on the antioxidant status. These results indicate that, in this particular model, EPA permitted platelets to have control levels of tocopherol, MDA and 12-HETE despite diamide treatment. Low concentrations of EPA might have prevented the increase of lipid hydroperoxides and especially the transient accumulation of 12-hydroperoxyeicosatetraenoic acid (12-HPETE).

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

PubMed1992

In vivo inhibition of basal and estrogen-induced phospholipase A2 activities by the triphenylethylene antiestrogen, tamoxifen, in immature quail oviduct.

The effects of tamoxifen on oviductal phospholipase A2 activity were studied in immature quails. Injected alone, from 0.1 to 10 mg/kg tamoxifen significantly reduced basal phospholipase A2 activity 6 h after the injection, independently of the dose used. At 24 h, maximal inhibition (-50%) was observed with 0.1 mg/kg tamoxifen, while higher doses were less effective. Combined with estradiol benzoate, tamoxifen reduced even below the control value (1 mg/kg for 24 h) the increase in phospholipase A2 activity induced by estrogen.

Animals↗

PubMed1992

Evidence for adenosine A2b receptors in the rat pineal gland.

We describe the effects of 5'-N-ethylcarboxamidoadenosine (NECA), a mixed A2a/A2b adenosine receptor agonist and 2-[p-(carboxyethyl)-phenylethylamino]-5'-N-ethylcarboxamidoaden osin e (CGS 21680), a selective A2a agonist, on cyclic AMP and N-acetylserotonin synthesis in rat pineal gland. NECA, 1 and 10 microM, increased cyclic AMP by 5- and 25-fold and N-acetylserotonin by 40- and 60-fold respectively, whereas CGS 21680 at the same concentrations was ineffective. These results argue for the presence of adenosine A2b receptors in rat pinealocytes.

Adenosine↗

PubMed1992

Selective modulation of the human platelet thromboxane A2/prostaglandin H2 receptor by eicosapentaenoic and docosahexaenoic acids in intact platelets and solubilized platelet membranes.

We previously demonstrated that nonesterified as well as esterified eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3) inhibit U46619-induced platelet aggregation and [3H]U46619 specific binding to washed human platelets. It was also demonstrated that esterification of these fatty acids resulted in a decrease in the affinity of [3H]U46619 for the thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptor. In order to investigate the specificity of this inhibition, the effects of 20:5n-3 and 22:6n-3 on the function and binding of the platelet alpha 2-adrenergic receptor were studied. It was found that neither 20:5n-3 nor 22:6n-3 (nonesterified or esterified) altered epinephrine-induced aggregation or [3H]yohimbine specific binding. Moreover, Scatchard analysis revealed that esterification with either 20:5n-3 or 22:6n-3 did not alter the dissociation constant for [3H]yohimbine binding. Modulation of the TXA2/PGH2 receptor by 20:5n-3 and 22:6n-3 was next evaluated using CHAPS- and digitonin-solubilized platelet membranes. [3H]SQ29,548 dissociation constants of 26.5 nM and 20.8 nM were measured for CHAPS and digitonin-solubilized membranes, respectively. Competitive binding experiments in these solubilized preparations revealed that 20:5n-3 or 22:6n-3 blocked [3H] SQ29,548 binding with IC50 values in the range of 6-15 microM, while concentrations of these fatty acids of up to 100 microM showed no effect on [3H]yohimbine binding. On the other hand, the IC50 values for inhibition of [3H] SQ29,548 binding by linoleic acid (18:2n-6) and gamma-linolenic acid (18:3n-6) were in the range of 150 microM. Furthermore, 18:2n-6 and 18:3n-6 showed similar inhibitory effects on [3H]yohimbine binding. Finally, competition binding studies performed in a partially purified TXA2/PGH2 receptor preparation also demonstrated inhibition of [3H]SQ29,548 binding by 20:5n-3 and 22:6n-3. Collectively, these findings support the notion that 20:5n-3 and 22:6n-3 can selectively and directly modulate TXA2/PGH2 receptor function, and that this mechanism of action may contribute to the antiplatelet activity associated with diets rich in these fatty acids.

Blood Platelets↗

PubMed1992

Diethyldithiocarbamate (ditiocarb sodium) effect on arachidonic acid metabolism in human mononuclear cells. Glutathione peroxidase-like activity.

Diethyldithiocarbamate (DTC), a thiol delivery agent, has been shown to significantly reduce the frequency of primary opportunistic infections in HIV-infected patients. This therapeutic effect has been related to the capacity of DTC to reverse the deleterious effects of the oxidative stress occurring in HIV infection. The influence of DTC on the oxygenated metabolism of arachidonic acid (AA) was investigated in mitogen-stimulated human peripheral blood mononuclear cells (PBMC). Upon incubation with PBMC previously labelled with [3H]AA, Concanavalin A (Con A) markedly increased cyclooxygenase and lipoxygenase activities, within 30 min, as judged by thromboxane B2 (TxB2) and hydroxyeicosatetraenoic acid (HETE) production. Con A activation of [3H]AA platelets also increased 12-HETE production but did not induce any TxB2 synthesis. Micromolar concentrations of DTC, added simultaneously with the mitogen, significantly enhanced the synthesis of HETEs above the Con A-induced level while TxB2-induced synthesis was inhibited but only at DTC concentrations higher than 50 microM. In the presence of nordihydroguaiaretic acid, a lipoxygenase inhibitor, which inhibited the Con A-induced synthesis of HETEs by 78%, DTC no longer stimulated HETE production above the Con A-induced level. Reverse phase HPLC analysis showed that Con A increased the PBMC production of 5-, 12- and 15-HETEs. In the presence of 5 microM DTC, 5-HETE production was entirely suppressed whereas the 15-HETE level was markedly enhanced, 12-HETE production by the contaminating platelets remained unchanged. In vitro experiments indicated that DTC alone did not significantly influence 15-hydroperoxyeicosatetraenoic (15-HPETE) production by the soybean 15-lipoxygenase but, in the presence of added reduced glutathione, DTC markedly reduced 15-HPETE into 15-HETE. In addition, DTC was able to substitute for cellular extract in the glutathione peroxidase (GPx) assay system. Taken together, these results indicate that DTC, through its "GPx-like" activity is able to modify the lipoxygenase cascade. Its ability to selectively reduce 15-HPETE known to stimulate immunosuppressive T-cells might help to explain its positive regulatory effect upon the immune system.

Arachidonic Acid↗

PubMed1992

Incorporation and turnover of eicosapentaenoic and docosahexaenoic acids in human blood platelets in vitro.

Mass changes in the incorporation of linoleic (C18:2), eicosapentaenoic (C20:5) and docosahexaenoic (C22:6) acids in human blood platelet phospholipids were induced by incubating the cells and these fatty acids complexed to albumin. The remodelling of [14C]C18:2, [14C]C20:5 and [14C]C22:6 in classes, subclasses and molecular species of platelet phospholipids was studied in resting and thrombin-stimulated cells. More than 85% of the incorporation was located in phospholipids, representing 5-fold and 2.5-fold increases in the phospholipid C20:5 and C22:6 endogenous content respectively. Thrombin stimulation induced a 30% degradation of 1-acyl-2-C20:5-glycerophosphocholine (GPC) and 1-acyl-2-C22:6-GPC, but did not induce significant release of C18:2 from 1-acyl-2-C18:2-GPC. There was no change in the [14C]fatty acid composition of 1-alkyl-2-acyl-GPC. Thrombin-dependent increases in 1-alkenyl-2-C20:5-glycerophosphoethanolamine (GPE) and 1-alkenyl-2-C22:6-GPE of 2.1-fold and 2.5-fold respectively accounted for the rise in GPE radioactivity and partly compensated for the loss of these fatty acids from 1,2-diacyl-GPC: transfer to 1-alkenyl-2-acyl-GPE was 0.4 and 1.5 nmol/10(9) platelets for C20:5 and C22:6 respectively. [14C]C20:5 and [14C]C22:6 were incorporated into six different species of 1,2-diacyl-GPC, with acylation in the major endogenous forms (C18:1 +C16:0 and C18:0 species) representing 76% and 66% respectively of the total radioactivity present in 1,2-diacyl-GPC. Stimulation by thrombin induced significant release of these fatty acids from the main molecular species of 1,2-diacyl-GPC, but significantly stimulated the synthesis of alkenyl forms of GPE containing C18:1/C22:6 +C16:0/C22:6, C18:0/C22:6 and C18:0/C20:5. C18:0/C18:2, the major endogenous C18:2 molecular species, represented only 10.5% of the incorporation; none of the [14C]C18:2 molecular species was a substrate for transfer towards 1-alkenyl-2-acyl-GPE. It is concluded that when C20:5 and C22:6, but not C18:2, are acylated in 1,2-diacyl-GPC, they participate in thrombin-dependent phospholipid remodelling, and might compete with the turnover and release of arachidonic acid from platelet phospholipids and the subsequent activation of the cells.

Blood Platelets↗

PubMed1992

Early increase in lymphocyte cyclic nucleotide phosphodiesterase activity upon mitogenic activation of human peripheral blood mononuclear cells.

Cyclic nucleotide phosphodiesterase activity of human peripheral blood mononuclear cells was significantly increased following a short (30 min) incubation with the mitogenic lectin Concanavalin A. Con A stimulated phosphodiesterase activity to the same extent whatever the subcellular compartment (homogenate, cytosol or pellet). Further separation of the Con A-activated mononuclear cells into lymphocyte-enriched and monocyte-enriched populations showed that the Con A-induced increase of phosphodiesterase activity exclusively affected the lymphocyte-enriched population. In lymphocytes, cyclic GMP phosphodiesterase activity was more importantly enhanced by Con A (+275%) than cyclic AMP phosphodiesterase activity (+75%). The increase of both activities occurred as early as from 10 min of Con A incubation and proved to be maximal with Con A doses of 2.5 and 5 micrograms per 10(6) cells, lower and higher doses being less effective. Inhibition experiments with reference inhibitors suggested that, among the high affinity phosphodiesterase isoforms, the cyclic GMP-inhibited enzyme might be more selectively enhanced by Con A than the cyclic AMP-specific, Rolipram-sensitive one. The non-mitogenic lectin Helix pomatia hemagglutinin, was not able to enhance cyclic nucleotide phosphodiesterase activity of human mononuclear cells whereas anti-CD3 monoclonal antibody, although being less effective than Con A, exhibited a significant stimulatory effect. Putting together these results suggest that the early increase in phosphodiesterase activity might be a normal step involved in the mitogenic activation of human lymphocyte.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1992

Modulation of cyclic nucleotide phosphodiesterase by dietary fats in rat heart.

Feeding oils of different fatty acid composition modifies the fatty acid composition of cardiac membrane phospholipids, thereby inducing changes in cardiac contractility and altering response of adenylate cyclase to catecholamines. In the present study, the effect of such dietary manipulations on cyclic nucleotide phosphodiesterase, which is involved in the control of cyclic nucleotide intracellular levels and in the control of cardiac contractility, was investigated. Rats were fed either a saturated fatty acid-enriched diet (8 weight percent [%] coconut oil + 2% sunflower oil), an n-6 fatty acid-enriched diet (10% sunflower oil) or an n-3 fatty acid-enriched diet (8% fish oil + 2% sunflower oil). The fatty acid composition of cardiac phospholipids, as well as the nonesterified fatty acid content of heart were markedly altered by the diets. The 18:2n-6 and 20:4n-6 content of cardiac phospholipids was markedly (-49%) depressed by fish oil as compared with sunflower oil feeding, but the nonesterified fatty acid level of heart membrane was lowest in coconut oil-fed rats. In addition, fish oil feeding more drastically depressed the n-6/n-3 fatty acid ratio in the nonesterified fatty acid pool than in cardiac phospholipids. Cyclic AMP phosphodiesterase activity was the lowest in both the particulate and soluble fractions of heart from rats fed sunflower oil, whereas cyclic GMP phosphodiesterase activity was not altered by the diets. Cyclic AMP phosphodiesterase activity was decreased by 18 and 12% in heart membranes of the sunflower oil group as compared to that of the coconut oil and fish oil groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1992

Age-related changes in arachidonic acid peroxidation and glutathione-peroxidase activity in human platelets.

Lipid peroxidation, vitamin E level and glutathione-peroxidase activity were determined in platelets from elderly (greater than 68 years) and young (21-43 years) people. To further assess the platelet lipid peroxidation, the metabolism of endogenous arachidonic acid in unstimulated platelets as well as that of the exogenous one were measured in the two groups. The oxygenated metabolites of arachidonic acid were enhanced in the elder population under both conditions tested. In addition, the platelet malondialdehyde content, a marker of the overall lipid peroxidation, was also found significantly increased in platelets from aged subjects. On the other hand, the platelet vitamin E level and the glutathione-peroxidase activity were significantly depressed in the elder group compared to the young one. These results suggest that the increased platelet activation observed with age could be linked to the accumulation of lipoxygenase-dependent peroxides associated with the decreased antioxidative defence of the cells, especially glutathione-peroxidase activity.

Adult↗

PubMed1992

Leukotriene B4 level in stimulated blood neutrophils and alveolar macrophages from healthy and asthmatic subjects. Effect of beta-2 agonist therapy.

Leukotriene B4 levels were measured after stimulation by calcium ionophore A23187: (i) in peripheral, neutrophils (PMN) from allergic asthmatics, rhinitis and healthy subjects; (ii) in macrophages collected by bronchoalveolar lavage. LTB4 levels in PMNs were significantly higher in non-treated allergic asthmatics and non-treated subjects with rhinitis compared to controls. Beta-2 agonist-treated asthmatics showed a significantly decreased LTB4 production which was not different from those of controls. In vitro, LTB4 production decreased significantly after PMN incubation with Salbutamol (10(-6) mol l-1). LTB4 produced by AM collected by BAL was measured in non-treated (n = 5) and treated (n = 11) asthmatics with inhaled beta-2 agonist. AM collected from all controls and non-treated asthmatics produced LTB4. By contrast, no production of LTB4 was observed in the treated group. LTB4 production decreased when normal AM were incubated in vitro with Salbutamol (10(-8) mol l-1). These results suggest that biochemical differences occur in PMN and macrophages from subjects treated with beta-2 agonist, presumably in changing the 5-lipoxygenase pathway.

Adult↗

PubMed1992

Unsaturated fatty acids esterified in 2-acyl-l-lysophosphatidylcholine bound to albumin are more efficiently taken up by the young rat brain than the unesterified form.

The aim of the present study was to investigate whether unsaturated 2-acyl-lysophosphatidylcholine bound to plasma albumin is a relevant delivery form of unsaturated fatty acids to the developing brain. Twenty-day-old rats were perfused for 30 s with labeled palmitic, oleic, linoleic, and arachidonic acids in either their unesterified form or esterified in 2-acyl-lysophosphatidylcholine labeled on the choline and fatty acid moieties. Both forms were bound to albumin. Incorporation in brain lipid classes was followed within 1 h. The brain uptake of the unesterified fatty acids reached a plateau at 5-15 min and was maximal for arachidonic acid (0.45% of the perfused dose). The brain uptake of palmitoyl-lysophosphatidylcholine was similar to that of palmitic acid, whereas that of other lysophosphatidylcholines increased with the degree of unsaturation (rate and maximal uptake) and was six- to 10-fold higher than that of the corresponding unesterified fatty acid. 2-Acyl-lysophosphatidylcholines were taken up without prior hydrolysis and reacylated into doubly labeled phosphatidylcholine, which was the most labeled lipid class, whereas lipid distribution of the unesterified fatty acid was more diversified. Partial hydrolysis of 2-acyl-lysophosphatidylcholine occurred in the brain tissue, and redistribution of the fatty acyl moiety into other phospholipid classes was also observed and was the highest for arachidonic acid. In this case, the percentage of esterification of this fatty acid in phosphatidylinositol (expressed as a percentage of the total lipid fraction) was relatively lower than that observed when the unesterified form was used.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

12-HETE inhibits the binding of PGH2/TXA2 receptor ligands in human platelets.

12(S)-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE), the end-lipoxygenase product of arachidonic acid in platelets has been previously shown to prevent PGH2/TxA2-induced aggregation. From the present study, we show that 12-HETE inhibits the binding of [125I]-PTA-OH, a thromboxane antagonist, to platelet membranes with an IC50 of 8 microM. This value is in accordance with previously reported 12-HETE concentrations required to prevent the aggregation induced by TxA2 mimetics, the methano analogues of PGH2, U44069 and U46619. When [3H]-U44069 was used as a thromboxane agonist to label intact platelets, 12-HETE also inhibited its binding. We conclude that part of the inhibitory effect of 12-HETE on PGH2/TxA2-induced aggregation might be the result of interacting with PGH2/TxA2 receptor sites.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

PubMed1991

Leukotriene B4 level in neutrophils from allergic and healthy subjects stimulated by low concentration of calcium ionophore A23187. Effect of exogenous arachidonic acid and possible endogenous source.

Peripheral blood neutrophils from patients with allergic rhinitis and from normal subjects were incubated for 5 min at 37 degrees C with 0.15 microM calcium ionophore A23187 in the absence or presence of exogenous arachidonic acid (2.5 to 10 microM). In neutrophils from allergic patients, the leukotriene B4 (LTB4) level was significantly increased by exogenous arachidonic acid in a concentration-dependent manner (16.2 +/- 4.2 and 38.1 +/- 6.8 pmol/5 min per 2 X 10(6) cells in the absence and presence of 10 microM arachidonic acid, respectively; P less than 0.005; n = 8). The LTB4 level in neutrophils from healthy subjects was only 0.97 +/- 0.17 pmol/5 min per 2 x 10(6) cells (n = 5) and was not enhanced by exogenous arachidonate. When cells from allergic patients were challenged in the presence of exogenous [1-14C]arachidonic acid, released LTB4 was radiolabeled and the incorporated radioactivity increased with the labeled arachidonate concentration. Labeled LTB4 was never detectable after incubating neutrophils from normal donors with exogenous labeled arachidonate. When neutrophils were incubated with [1-14C]arachidonate for 1 h, the different lipid pools of the two cell populations were labeled but both types of neutrophils produced unlabeled LTB4 in response to ionophore stimulation. The hydrolysis of choline and ethanolamine phospholipids into diacyl-, alkenylacyl- and alkylacyl-species revealed that solely the alkylacyl-subclass of phosphatidylcholine was unlabeled. We conclude (i) that neutrophils from allergic patients stimulated by low ionophore concentration produce more LTB4 than neutrophils from healthy subjects and incorporate exogenous arachidonate, (ii) that endogenous arachidonate converted to LTB4 by the 5-lipoxygenase pathway may provide only from 1-O-alkyl-2-arachidonoyl-glycero-3-phosphocholine.

Adult↗

PubMed1991

Differential regulation of calmodulin-dependent and -independent cyclic AMP phosphodiesterases from oviduct by fatty acids.

Regulation of calmodulin-independent and -dependent cAMP phosphodiesterases from quail oviduct by various fatty acids was studied. The calmodulin-independent form was slightly activated by low concentrations (20 microM) of oleic, linoleic and arachidonic acid, higher concentrations were inhibitory. The basal activity of the calmodulin-dependent form was activated by linoleic acid and to a lesser extent by arachidonic acid at low concentrations and inhibited by higher concentrations of the two fatty acids. In contrast, arachidonic acid was a potent reversible inhibitor of calmodulin in the activation of this enzyme (IC50: 20 microM) whereas linoleic acid was inactive from 10 to 150 microM. The present results strongly suggest that the differential regulation of cAMP phosphodiesterases by these fatty acids could profoundly influence the level of cAMP in the oviduct and thus its subsequent effects.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1991

Docosahexaenoic acid (cervonic acid) incorporation into different brain regions in the awake rat.

A quantitative method is presented to examine the localization, in individual brain regions of awake rats, of docosahexaenoic acid (22:6 n-3 or cervonic acid), the main polyunsaturated fatty acid of the nervous system together with arachidonic acid. Following the intravenous injection of 10 microCi [14C]22:6 n-3 (around 0.2 mumol/rat). 0.11-0.28% of the initial radioactivity was located in specific brain areas after detection from 10 to 240 min. Brain regional radioactivity determined by quantitative autoradiography indicated that 60 min after injection, [14C]22:6 n-3 concentrations ranged from 13.75 nCi/g of tissue in inferior olive to 5.59 nCi/g in frontal cortex. The results indicate a higher incorporation into the auditory system: inferior colliculus, central cochlear nucleus, lateral lemniscus, into neuroendocrine structures: paraventricular and supraoptic nuclei, and into certain circumventricular organs such as the pineal gland and neurohypophysis. Analysis of the Bligh and Dyer lipid extracts of rat brain revealed that 60 min after injection, 80-85% of the radioactivity was in choline and ethanolamine phosphoglycerides. These observations suggest that intravenous injection of [14C]22:6 n-3 may be used to study the brain lipid compartmental metabolism in vivo in order to visualize alterations of structural lipid components.

Animals↗

PubMed1991

Fatty acid composition of the rat pineal gland. Dietary modifications.

When compared to brain, the fatty acid composition of the rat pineal gland revealed that the total proportion of n-6 polyunsaturated fatty acids (PUFA) was 2.3-fold higher, whereas the proportion of n-3 fatty acids was similar. Specifically, 20:4(n-6) and 18:2(n-6) were respectively 1.56- and 11.80-fold higher in the pineal than in the brain, while the proportions of 22:6(n-3) were similar in both tissues. In addition, 18:1(n-9) was found 2.15-fold lower in the pineal. Feeding adult rats with fish oil concentrates induced a significant alteration of the polyunsaturated fatty acid composition of the pineal. There was a reciprocal replacement of the n-6 by the n-3 fatty acids. Conversely, in rats fed a n-3 fatty acid-deficient diet (sunflower oil or coconut oil diet), the pineal gland contained reduced proportions of n-3 fatty acids. We conclude that the pineal gland (i) differs from the brain in containing much higher proportions of 18:2(n-6) and from the other tissues for its high proportions of 22:6(n-3) and (ii) is highly sensitive to the n-3 fatty acid diet in contrast to what is known for the brain. These findings are discussed in the context of melatonin biosynthesis, the major hormone of the pineal gland.

Animals↗

PubMed1991

Decrease in platelet reduced glutathione increases lipoxygenase activity and decreases vitamin E.

Unstimulated normal human blood platelets were treated with azodicarboxylic acid bis(dimethylamide) (diamide), a thiol-oxidizing agent. Oxygenated arachidonic acid (AA) metabolites, malondialdehyde (MDA), and tocopherols were then quantified by high-performance liquid chromatography (HPLC). Diamide treatment partially decreased the amount of reduced glutathione (GSH) content and induced a subsequent decrease in peroxidase activity. However, formation of 12-hydroxy-eicosatetraenoic acid (12-HETE), the end-product of lipoxygenation of AA, increased. Formation of MDA, a marker of overall lipid peroxidation, was also enhanced. Furthermore, platelet alpha-tocopherol, but not gamma-tocopherol, significantly decreased. These results indicate that enhanced "basal" lipoxygenase activity, as a marker of specific AA oxygenation, may be linked to decreased platelet antioxidant status.

Antioxidants↗

PubMed1991

Distribution of tritium labeled 12(S) hydroxy-eicosatetraenoic acid (12-HETE) in the rat.

The in vivo metabolism of 12-(S)-Hydroxy-eicosatetraenoic acid (12-HETE), the end-lipoxygenase product of arachidonic acid in platelets, has been investigated in the rat. Fifty microcuries of 5,6-[3H]-12-HETE (50 Ci/mmol) were injected to anesthetized rats and the radioactivity was followed in plasma. At the end of the experiment, various organs of the animal were removed and the radioactivity attached to them was determined. The label of the plasma plateaued to approximately one third of the initial radioactivity ten minutes after the injection. Among the various organs tested (brain, heart, intestine, kidney, liver, lungs, spleen, testis/uterus) the kidney was far the most active to accumulate 12-HETE and/or its labeled metabolites, and no radioactivity could be detected in urine during the course of the experiment. The analysis of lipid extracts from the various tissues revealed that 12-HETE was not accumulating in its unesterified form but was likely bound to phospholipids. We conclude that, although the label providing from the initial 12-HETE did not completely disappear from plasma, circulating 12-HETE cannot be considered as a circulating marker of cell activation.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗