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Prostaglandins & Other Lipid Mediators Dec 2019Platelet activation plays an important role in acute and chronic cardiovascular disease states. Multiple pathways contribute to platelet activation including those... (Review)
Review
Platelet activation plays an important role in acute and chronic cardiovascular disease states. Multiple pathways contribute to platelet activation including those dependent upon arachidonic acid. Arachidonic acid is released from the platelet membrane by phospholipase A2 action and is then metabolized in the cytosol by specific arachidonic acid oxidation enzymes including prostaglandin H synthase, 12-lipoxygenase, and cytochrome P450 to produce pro- and anti-inflammatory eicosanoids. This review aims to analyze the role of arachidonic acid oxidation on platelet activation, the enzymes that use it as a substrate associated as novel therapeutics target for antiplatelet drugs.
Topics: Animals; Arachidonate 12-Lipoxygenase; Arachidonic Acid; Blood Platelets; Cell Membrane; Cytochrome P-450 Enzyme System; Cytosol; Humans; Oxidation-Reduction; Phospholipases A2; Platelet Activation; Prostaglandin-Endoperoxide Synthases
PubMed: 31634570
DOI: 10.1016/j.prostaglandins.2019.106382 -
Life Sciences Mar 2022Endothelial cells are characterized by intense metabolic activity and control of homeostasis. Exposure to benzo(a)pyrene (BaP) plays an important role in the etiology of...
Endothelial cells are characterized by intense metabolic activity and control of homeostasis. Exposure to benzo(a)pyrene (BaP) plays an important role in the etiology of atherosclerosis. The study aimed to determine the effect of arachidonic (ARA), and eicosapentaenoic acid (EPA) on pro-inflammatory gene and protein levels in human umbilical vein endothelial cells (HUVEC) exposed to BaP. Cyclooxygenase-2 (COX-2), aryl hydrocarbon receptor (AHR), and glutathione S transferase Mu1 (GSTM1) proteins expression were analyzed by Western blot. Prostaglandin synthase 2 (PTGS2), AHR, GSTM1, phospholipase A2 (PLA2G4A), cytochrome P450 CYP1A1, intercellular adhesion molecule-1 (ICAM-1), endothelial nitric-oxide synthase (NOS3), and vascular adhesion molecule-1 gene expression (VCAM-1) was analyzed in Real time-qPCR. Phospholipase A2 activity was measured using the ELISA technique, and CYP1A1 activity was analyzed in luminescence assay. The highest amount of COX-2, the most increased activity of CYP1A1 and cPLA2, and overexpression of GSTM1, CYP1A1, ICAM-1, and VCAM-1 gene was observed in HUVEC cells treated with BaP. After co-treatment with BaP and ARA or EPA, an increase of GSTM1 level was observed. Incubation of endothelial cells with ARA or EPA and BaP resulted in lower CYP1A1 and cPLA2 activities and lower expression of VCAM-1 and ICAM-1 genes. Significant overexpression of AHR, GSTM1, CYP1A1, PTGS2, PLA2G4A, and NOS3 genes was noted in cells treated with EPA and BaP. Our data suggest a beneficial effect of EPA and ARA on endothelial function. Thus, it justifies further research on the participation of fatty acids in the regulation of physiological and pathological processes in endothelial cells.
Topics: Arachidonic Acid; Benzo(a)pyrene; Cell Survival; Cytochrome P-450 CYP1A1; Dose-Response Relationship, Drug; Eicosapentaenoic Acid; Human Umbilical Vein Endothelial Cells; Humans
PubMed: 35065163
DOI: 10.1016/j.lfs.2022.120345 -
Journal of Atherosclerosis and... Jun 2023
Topics: Humans; Arachidonic Acid; East Asian People; Eicosapentaenoic Acid; Independent Living; Risk Factors
PubMed: 36682774
DOI: 10.5551/jat.ED222 -
Prostaglandins & Other Lipid Mediators Dec 2019Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock, the most common form of vasodilatory shock, is a subset... (Review)
Review
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock, the most common form of vasodilatory shock, is a subset of sepsis in which circulatory and cellular/metabolic abnormalities are severe enough to increase mortality. Inflammatory shock constitutes the hallmark of sepsis, but also a final common pathway of any form of severe long-term tissue hypoperfusion. The pathogenesis of inflammatory shock seems to be due to circulating substances released by pathogens (e.g., bacterial endotoxins) and host immuno-inflammatory responses (e.g., changes in the production of histamine, bradykinin, serotonin, nitric oxide [NO], reactive nitrogen and oxygen species, and arachidonic acid [AA]-derived eicosanoids mainly through NO synthase, cyclooxygenase, and cytochrome P450 [CYP] pathways, and proinflammatory cytokine formation). Therefore, refractory hypotension to vasoconstrictors with end-organ hypoperfusion is a life threatening feature of inflammatory shock. This review summarizes the current knowledge regarding the role of eicosanoids derived from CYP pathway of AA in animal models of inflammatory shock syndromes with an emphasis on septic shock in addition to potential therapeutic strategies targeting specific CYP isoforms responsible for proinflammatory/anti-inflammatory mediator production.
Topics: Animals; Arachidonic Acid; Cytochrome P-450 Enzyme System; Cytokines; Humans; Inflammation; Inflammation Mediators; Nitric Oxide Synthase; Shock
PubMed: 31586592
DOI: 10.1016/j.prostaglandins.2019.106377 -
Molecules (Basel, Switzerland) Jun 2022Inflammation plays a crucial role in the initiation and development of a wide range of systemic illnesses. Epoxyeicosatrienoic acids (EETs) are derived from arachidonic... (Review)
Review
Inflammation plays a crucial role in the initiation and development of a wide range of systemic illnesses. Epoxyeicosatrienoic acids (EETs) are derived from arachidonic acid (AA) metabolized by CYP450 epoxygenase (CYP450) and are subsequently hydrolyzed by soluble epoxide hydrolase (sEH) to dihydroxyeicosatrienoic acids (DHETs), which are merely biologically active. EETs possess a wide range of established protective effects on many systems of which anti-inflammatory actions have gained great interest. EETs attenuate vascular inflammation and remodeling by inhibiting activation of endothelial cells and reducing cross-talk between inflammatory cells and blood vessels. EETs also process direct and indirect anti-inflammatory properties in the myocardium and therefore alleviate inflammatory cardiomyopathy and cardiac remodeling. Moreover, emerging studies show the substantial roles of EETs in relieving inflammation under other pathophysiological environments, such as diabetes, sepsis, lung injuries, neurodegenerative disease, hepatic diseases, kidney injury, and arthritis. Furthermore, pharmacological manipulations of the AA-CYP450-EETs-sEH pathway have demonstrated a contribution to the alleviation of numerous inflammatory diseases, which highlight a therapeutic potential of drugs targeting this pathway. This review summarizes the progress of AA-CYP450-EETs-sEH pathway in regulation of inflammation under different pathological conditions and discusses the existing challenges and future direction of this research field.
Topics: Anti-Inflammatory Agents; Arachidonic Acid; Cytochrome P-450 Enzyme System; Eicosanoids; Endothelial Cells; Epoxide Hydrolases; Humans; Inflammation; Neurodegenerative Diseases
PubMed: 35744996
DOI: 10.3390/molecules27123873 -
BioTechniques Jun 2022Clinical and epidemiological studies suggest that analysis of the polyunsaturated fatty acids (PUFAs) is essential to evaluate nutritional requirements and disease...
Clinical and epidemiological studies suggest that analysis of the polyunsaturated fatty acids (PUFAs) is essential to evaluate nutritional requirements and disease risk. We describe a simple, sensitive and non-invasive method for estimating the n-3 index and arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio in dried blood spots (DBSs). After obtaining DBSs on a spot card, PUFAs were transesterified (direct, acidic transesterification) and subsequently extracted with n-hexane. Gas chromatography with flame ionization detection (GC-FID) was used to analyze the extracted PUFAs, and then n-3 index and AA/EPA ratio were calculated. Method validation showed satisfactory precision and linearity. This analysis is simple and reliable to estimate PUFA status, and it was successfully applied to samples from 20 subjects, demonstrating its applicability.
Topics: Arachidonic Acid; Chromatography, Gas; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; Humans
PubMed: 35698842
DOI: 10.2144/btn-2021-0109 -
Current Opinion in Clinical Nutrition... May 2024For many decades, docosahexaenoic acid (DHA) supplementation was tested in premature infants to achieve an intake equivalent to the average level in breast milk, but... (Review)
Review
PURPOSE OF REVIEW
For many decades, docosahexaenoic acid (DHA) supplementation was tested in premature infants to achieve an intake equivalent to the average level in breast milk, but this approach has led to conflicting results in terms of development and health outcomes. Higher doses of DHA closer to fetal accumulation may be needed.
RECENT FINDINGS
The efficacy of DHA supplementation for preterm infants at a dose equivalent to the estimated fetal accumulation rate is still under investigation, but this may be a promising approach, especially in conjunction with arachidonic acid supplementation. Current data suggest benefit for some outcomes, such as brain maturation, long-term cognitive function, and the prevention of retinopathy of prematurity. The possibility that supplementation with highly unsaturated oils increases the risk of neonatal morbidities should not be ruled out, but current meta-analyzes do not support a significant risk.
SUMMARY
The published literature supports a DHA intake in preterm infants that is closer to the fetal accumulation rate than the average breast milk content. Supplementation with DHA at this level in combination with arachidonic acid is currently being investigated and appears promising.
Topics: Infant; Female; Infant, Newborn; Humans; Infant, Premature; Docosahexaenoic Acids; Arachidonic Acid; Milk, Human; Dietary Supplements
PubMed: 38547330
DOI: 10.1097/MCO.0000000000001035 -
Drug Metabolism Reviews 2023The incidence of heart failure (HF) is generally preceded by cardiac hypertrophy (CH), which is the enlargement of cardiac myocytes in response to stress. During CH, the... (Review)
Review
The incidence of heart failure (HF) is generally preceded by cardiac hypertrophy (CH), which is the enlargement of cardiac myocytes in response to stress. During CH, the metabolism of arachidonic acid (AA), which is present in the cell membrane phospholipids, is modulated. Metabolism of AA gives rise to hydroxyeicosatetraenoic acids (HETEs) and epoxyeicosatrienoic acids (EETs) cytochrome P450 (CYP) ω-hydroxylases and CYP epoxygenases, respectively. A plethora of studies demonstrated the involvement of CYP-mediated AA metabolites in the pathogenesis of CH. Also, inflammation is known to be a characteristic hallmark of CH. In this review, our aim is to highlight the impact of inflammation on CYP-derived AA metabolites and CH. Inflammation is shown to modulate the expression of various CYP ω-hydroxylases and CYP epoxygenases and their respective metabolites in the heart. In general, HETEs such as 20-HETE and mid-chain HETEs are pro-inflammatory, while EETs are characterized by their anti-inflammatory and cardioprotective properties. Several mechanisms are implicated in inflammation-induced CH, including the modulation of NF-κB and MAPK. This review demonstrated the inflammatory modulation of cardiac CYPs and their metabolites in the context of CH and the anti-inflammatory strategies that can be employed in the treatment of CH and HF.
Topics: Humans; Cardiomegaly; Cytochrome P-450 Enzyme System; Heart; Arachidonic Acid; Hydroxyeicosatetraenoic Acids; Inflammation; Heart Failure
PubMed: 36573379
DOI: 10.1080/03602532.2022.2162075 -
Ultrasonics Sonochemistry Oct 2021Ultrasound assisted enzymatic method was applied to the degumming of arachidonic acid (ARA) oil produced by Mortierella alpina. The conditions of degumming process were...
Ultrasound assisted enzymatic method was applied to the degumming of arachidonic acid (ARA) oil produced by Mortierella alpina. The conditions of degumming process were optimized by response surface methodology with Box- Behnken design. A dephosphorization rate of 98.82% was achieved under optimum conditions of a 500 U/kg of Phospholipase A (PLA) dosage, 2.8 mL/100 g of water volume, 120 min of ultrasonic time, and 135 W of ultrasonic power. The phosphorus content of ultrasonic assisted enzymatic degumming oil (UAEDO) was 4.79 mg/kg, which was significantly lower than that of enzymatic degumming oil (EDO, 17.98 mg/kg). Crude Oil (CO), EDO and UAEDO revealed the similar fatty acid compositions, and ARA was dominated (50.97 ~ 52.40%). The oxidation stability of UAEDO was equivalent to EDO and weaker than CO, while UAEDO presented the strongest thermal stability, followed by EDO and CO. Furthermore, aldehydes, acids and alcohols were identified the main volatile flavor components for the three oils. The proportions of major contributing components such as hexanal, nonanal, (E)-2-nonanal, (E, E)-2,4-decadienal, (E)-2-nonenal and aldehydes in UAEDO and EDO were all lower than CO. Overall, Ultrasound assisted enzymatic degumming proved to be an efficient and superior method for degumming of ARA oil.
Topics: Aldehydes; Arachidonic Acid; Fatty Acids; Mortierella; Plant Oils; Ultrasonic Waves; Water
PubMed: 34469850
DOI: 10.1016/j.ultsonch.2021.105720 -
Clinical Nutrition (Edinburgh, Scotland) Jun 2023Preterm infants risk deficits of long-chain polyunsaturated fatty acids (LCPUFAs) that may contribute to morbidities and hamper neurodevelopment. We aimed to determine... (Randomized Controlled Trial)
Randomized Controlled Trial
Modification of serum fatty acids in preterm infants by parenteral lipids and enteral docosahexaenoic acid/arachidonic acid: A secondary analysis of the Mega Donna Mega trial.
BACKGROUND & AIM
Preterm infants risk deficits of long-chain polyunsaturated fatty acids (LCPUFAs) that may contribute to morbidities and hamper neurodevelopment. We aimed to determine longitudinal serum fatty acid profiles in preterm infants and how the profiles are affected by enteral and parenteral lipid sources.
METHODS
Cohort study analyzing fatty acid data from the Mega Donna Mega study, a randomized control trial with infants born <28 weeks of gestation (n = 204) receiving standard nutrition or daily enteral lipid supplementation with arachidonic acid (AA):docosahexaenoic acid (DHA) (100:50 mg/kg/day). Infants received an intravenous lipid emulsion containing olive oil:soybean oil (4:1). Infants were followed from birth to postmenstrual age 40 weeks. Levels of 31 different fatty acids from serum phospholipids were determined by GC-MS and reported in relative (mol%) and absolute concentration (μmol l) units.
RESULTS
Higher parenteral lipid administration resulted in lower serum proportion of AA and DHA relative to other fatty acids during the first 13 weeks of life (p < 0.001 for the 25th vs the 75th percentile). The enteral AA:DHA supplement increased the target fatty acids with little impact on other fatty acids. The absolute concentration of total phospholipid fatty acids changed rapidly in the first weeks of life, peaking at day 3, median (Q1-Q3) 4452 (3645-5466) μmol l, and was positively correlated to the intake of parenteral lipids. Overall, infants displayed common fatty acid trajectories over the study period. However, remarkable differences in fatty acid patterns were observed depending on whether levels were expressed in relative or absolute units. For example, the relative levels of many LCPUFAs, including DHA and AA, declined rapidly after birth while their absolute concentrations increased in the first week of life. For DHA, absolute levels were significantly higher compared to cord blood from day 1 until postnatal week 16 (p < 0.001). For AA, absolute postnatal levels were lower compared to cord blood from week 4 throughout the study period (p < 0.05).
CONCLUSIONS
Our data show that parenteral lipids aggravate the postnatal loss of LCPUFAs seen in preterm infants and that serum AA available for accretion is below that in utero. Further research is needed to establish optimal postnatal fatty acid supplementation and profiles in extremely preterm infants to promote development and long-term health.
CLINICAL TRIAL REGISTRY
ClinicalTrials.gov, identifier: NCT03201588.
Topics: Infant; Infant, Newborn; Humans; Docosahexaenoic Acids; Fatty Acids; Arachidonic Acid; Cohort Studies; Infant, Extremely Premature; Phospholipids
PubMed: 37120902
DOI: 10.1016/j.clnu.2023.04.020