0000000000303428

AUTHOR

Philippe Durand

Acute methionine load‐induced hyperhomocysteinemia enhances platelet aggregation, thromboxane biosynthesis, and macrophage‐derived tissue factor activity in rats

A moderate elevation of plasma homocysteine is a risk factor for atherosclerosis and arterial and veinous thrombosis. However, the mechanisms leading to vascular disorders are poorly understood because studies that have investigated the potential atherothrombogenicity of hyperhomocysteinemia in vivo are scarce. Using a rat model, we were the first to show that dietary folic acid deficiency, a major cause of basal hyperhomocysteinemia, is associated with enhanced macrophage-derived tissue factor and platelet activities. We proposed that an homocysteine-induced oxidative stress may account for this hypercoagulable state. To determine the true thrombogenicity of moderate hyperhomocysteinemia a…

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Folate deficiencies and cardiovascular pathologies.

Abstract Although folates are widely distributed in foods, folate deficiencies may be more frequent than expected because their true availability may be impaired due to their lability under various food cooking and processing conditions. Folate deficiency is frequently observed in elderly people, smokers, alcoholics and oral contraceptive users. It is also associated with the mutation leading to the thermolabile variant of N5, 10-methylenetetrahydrofolate reductase which is observed in about 10 % of the population. In addition to the essential role of the intracellular pool of polyglutamates in de novo biosynthesis of deoxyribonucleotides which allow cell growth and division, the reduced an…

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Enhanced platelet thromboxane synthesis and reduced macrophage-dependent fibrinolytic activity related to oxidative stress in oral contraceptive-treated female rats.

Abstract In previous studies conducted in rats and in women, we have shown that oral contraceptive (OC) administration induced a platelet hyperaggregation simultaneously with an increased platelet lipid biosynthesis which might be related to lipid peroxidation. In the present study, we specifically studied the arachidonic acid and the fibrinolytic pathways in relation to the fatty acid composition in female rats treated for 6 weeks with OC (ethinyl estradiol plus lynestrenol). We found that platelets of treated animals were not only hyper-responsive to thrombin and ADP, but also to sodium arachidonate. In addition, the results of the thrombin-induced release of labeled arachidonic acid pre-…

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Déficiences en folates et pathologie cardiovasculaire

Resume Bien que les folates soient largement distribues dans l'alimentation, ils sont sensibles a de nombreuses agressions physicochimiques qui reduisent fortement leur biodisponibilite. Ainsi, contrairement aux idees recues, la deficience en folates concernerait une proportion importante de la population occidentale. La deficience en folates est frequemment observee chez les personnes âgees, les fumeurs et les alcooliques, lors de l'utilisation de certaines medications telles que le methotrexate, les anticonvulsifs et les œstroprogestatifs synthetiques ainsi que lors de la mutation thermolabile de la N 5,10 -methylenetetrahydrofolate reductase. A cote du role majeur du pool intracellulaire…

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Long-term moderate magnesium-deficient diet shows relationships between blood pressure, inflammation and oxidant stress defense in aging rats

International audience; Epidemiological and experimental studies have indicated a relationship among aging, dietary Mg, inflammatory stress, and cardiovascular disease. Our aim in the present study was to investigate possible links between dietary Mg, oxidant stress parameters, and inflammatory status with aging in rats. We designed a long-term study in which rats were fed for 22 months with moderately deficient (150 mg/kg), standard (800 mg/kg), or supplemented (3200 mg/kg) Mg diets. Comparisons were made with young rats fed with the same diets for 1 month. Compared to the standard and supplemented diets, the Mg-deficient diet significantly increased blood pressure, plasma interleukin-6, f…

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Folic Acid Deficiency Enhances Oral Contraceptive-Induced Platelet Hyperactivity

Abstract In previous studies conducted in female rats and in women, oral contraceptives (OC) were found to induce a platelet hyperactivity that was related to an oxidative stress. Because cases of megaloblastic anemia have been reported to occur in women taking OC, these treatments are suspected of depleting folate stores. In the study presented herein, which was conducted in rats, we sought to determine the influence of dietary folic acid deficiency (FD) on the thrombogenicity of OC. Animals were fed for 6 weeks with either a folic acid-deficient diet (250 μg/kg folic acid) or a control diet (750 μg/kg). One-half of the animals in each group were treated with OC (ethinyl estradiol plus ly…

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Profile of Fatty Acids, Tocopherols, Phytosterols and Polyphenols in Mediterranean Oils (Argan Oils, Olive Oils, Milk Thistle Seed Oils and Nigella Seed Oil) and Evaluation of their Antioxidant and Cytoprotective Activities

Background: The effects of vegetable oils on human health depend on their components. Therefore, their profiles of lipid nutrients and polyphenols were determined. Objective: To establish and compare the fatty acid, tocopherol, phytosterol and polyphenol profiles of Mediterranean oils: cosmetic and dietary argan oils (AO; Morocco: Agadir, Berkane); olive oils (OO; Morocco, Spain, Tunisia); milk thistle seed oils (MTSO; Tunisia: Bizerte, Sousse, Zaghouane); nigella seed oil (NSO). Methods: The biochemical profiles were determined by gas chromatography-flame ionization, high performance liquid chromatography and gas chromatography, coupled with mass spectrometry as required. The antioxidant …

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Altérations du métabolisme de l'homocystéine et maladies cardiovasculaires

Resume L'homocysteine est un produit intermediaire du metabolisme de la methionine. L'augmentation moderee ou intermediaire de la concentration totale en homocysteine circulante, detectee dans les conditions basales ou apres le test de surcharge orale en methionine, est maintenant reconnue comme un facteur de risque important des maladies cardiovasculaires et des thromboses, chez les femmes comme chez les hommes, au meme titre que les facteurs de risques conventionnels. L'hyperhomocysteinemie, qui depend d'une inhibition de la voie de remethylation, d'une inhibition ou d'une saturation de la voie de transsulfuration, resulte d'une alteration de la regulation coordonnee du metabolisme de l'h…

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