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Analytical and Bioanalytical Chemistry Apr 2015Quantification of eicosanoids and oxylipins derived from other polyunsaturated fatty acids in biological samples is crucial for a better understanding of the biology of... (Review)
Review
Quantification of eicosanoids and oxylipins derived from other polyunsaturated fatty acids in biological samples is crucial for a better understanding of the biology of these lipid mediators. Moreover, a robust and reliable quantification is necessary to monitor the effects of pharmaceutical intervention and diet on the arachidonic acid (AA) cascade, one of today's most relevant drug targets. Low (sub-nanomolar) concentrations and a large number of structurally similar analytes, including regioisomers, require high chromatographic resolution and selective and sensitive mass spectrometry analysis. Currently, reversed-phase liquid chromatography in combination with detection on sensitive triple-quadrupole instruments, operating in selected reaction monitoring mode, is the main method of quantitative oxylipin analysis. A lack of standardized sample collection, handling, and preparation procedures, degradation of the analytes during sample preparation, and purity and availability of standards (internal standards) are the major problems of targeted metabolomics approaches for the AA cascade. Major challenges for instrumental analytical methods are the detection of esterified oxylipins, and separation and individual detection of oxylipin isomers. Solving these problems would help to further knowledge of the biology of lipid mediators, and is an important task for bio-analytical research.
Topics: Arachidonic Acid; Chromatography, Reverse-Phase; Esterification; Humans; Mass Spectrometry; Metabolomics; Oxylipins; Stereoisomerism
PubMed: 25577350
DOI: 10.1007/s00216-014-8369-4 -
Pharmacology & Therapeutics Jun 2023Platelets are small, anucleate cells in the blood that play a crucial role in the hemostatic response but are also implicated in the pathophysiology of cardiovascular... (Review)
Review
Platelets are small, anucleate cells in the blood that play a crucial role in the hemostatic response but are also implicated in the pathophysiology of cardiovascular disease. It is widely appreciated that polyunsaturated fatty acids (PUFAs) play an integral role in the function and regulation of platelets. PUFAs are substrates for oxygenase enzymes cyclooxygenase-1 (COX-1), 5-lipoxygenase (5-LOX), 12-lipoxygenase (12-LOX) and 15-lipoxygenase (15-LOX). These enzymes generate oxidized lipids (oxylipins) that exhibit either pro- or anti-thrombotic effects. Although the effects of certain oxylipins, such as thromboxanes and prostaglandins, have been studied for decades, only one oxylipin has been therapeutically targeted to treat cardiovascular disease. In addition to the well-known oxylipins, newer oxylipins that demonstrate activity in the platelet have been discovered, further highlighting the expansive list of bioactive lipids that can be used to develop novel therapeutics. This review outlines the known oxylipins, their activity in the platelet, and current therapeutics that target oxylipin signaling.
Topics: Humans; Oxylipins; Cardiovascular Diseases; Fatty Acids, Unsaturated; Hemostasis; Thrombosis
PubMed: 37100208
DOI: 10.1016/j.pharmthera.2023.108420 -
Journal of Chromatography. A Oct 2023Oxylipins and their precursors (long-chain polyunsaturated fatty acids, LCPUFAs) are key intercellular signaling molecules influencing the inflammatory response. Each...
Determination of oxylipins and their precursors in breast milk by solid phase extraction-ultra high performance liquid chromatography-triple quadrupole tandem mass spectrometry.
Oxylipins and their precursors (long-chain polyunsaturated fatty acids, LCPUFAs) are key intercellular signaling molecules influencing the inflammatory response. Each oxylipin has pro- and/or anti-inflammatory effects, and the relative abundance of different oxylipins can alter the inflammatory balance, making it important to clarify the oxylipin profile of breast milk for optimal infant health. The extraction, identification, and simultaneous quantification of oxylipins in breast milk are challenging due to the structural similarity, limited stability, and the low endogenous concentration of oxylipins and the complex matrix of breast milk. This study aimed to develop a solid phase extraction-ultra high performance liquid chromatography-triple quadrupole tandem mass spectrometry (SPE-UPLC-MS/MS) method for the comprehensive and specific quantification of oxylipins and their precursors in breast milk. The LC conditions (including column, mobile phase, and gradient conditions) and SPE procedure (including SPE cartridges, elution solvent, and elution volume) were optimized to achieve accurate quantification and better analyte recovery. A single 18-minute chromatographic run allows for the quantification of 20 oxylipins and 5 PUFAs. The results showed good linearity (R > 0.99) over the concentration range of 2 to 100 ng/mL, with the instrument detection limits ranging from 0.01 to 0.90 ng/mL for oxylipins and 0.02 to 0.59 ng/mL for PUFAs. The method is rapid, sensitive, and reproducible (RSD ≤ 10%) and is suitable for the quantitative analysis of oxylipins and their precursors in infant formula samples.
Topics: Humans; Female; Milk, Human; Oxylipins; Chromatography, High Pressure Liquid; Tandem Mass Spectrometry; Chromatography, Liquid; Solid Phase Extraction; Fatty Acids, Unsaturated
PubMed: 37769518
DOI: 10.1016/j.chroma.2023.464400 -
Prostaglandins & Other Lipid Mediators Jan 2012There is a sufficient body of work documenting the distribution of 3-hydroxy oxylipins in microbes. However, there is limited information on the role of these compounds... (Review)
Review
There is a sufficient body of work documenting the distribution of 3-hydroxy oxylipins in microbes. However, there is limited information on the role of these compounds in microbial pathogenesis. When derived from mammalian cells, these compounds regulate patho-biological processes, thus an understanding of 3-hydroxy oxylipin function and metabolism could prove important in shedding light on how these compounds mediate cellular pathology and physiology. This could present 3-hydroxy oxylipin biosynthetic pathways as targets for drug development. In this minireview, we interrogate the relevant yeast and bacterial 3-hydroxy oxylipin literature in order to appreciate how these compounds may influence the inflammatory response leading to disease development.
Topics: Animals; Bacteria; Humans; Oxylipins; Yeasts
PubMed: 22108026
DOI: 10.1016/j.prostaglandins.2011.11.001 -
Journal of Pediatric Gastroenterology... Aug 2019Lipid emulsions used to support nutrition in preterm infants contain long-chain polyunsaturated fatty acids (LCPUFAs) as a source of essential fatty acids; these LCPUFAs...
Lipid emulsions used to support nutrition in preterm infants contain long-chain polyunsaturated fatty acids (LCPUFAs) as a source of essential fatty acids; these LCPUFAs and their parent polyunsaturated fatty acid (PUFA) can be oxidized by a variety of mechanisms to bioactive molecules called oxylipins, which are signaling molecules that initiate and/or resolve inflammation. The aim of this study was to explore levels of free LCPUFA and their related oxylipins in 3 commercially available lipid emulsions (Intralipid, SMOFlipid, and ClinOleic) using ultra high-performance liquid chromatography mass spectroscopy. Free LCPUFA were detected in all lipid emulsions tested. Seven, 8, and 9 different oxylipin compounds were detected in the 3 emulsions, respectively. The oxylipins detected were mainly derived from omega-6 PUFAs; these included 13-hydroxyoctadecadienoic acid from linoleic acid and 5-hydroxyeicosatetraenoic acid derived from arachidonic acid. It may be clinically important to know that oxylipins exist in lipid emulsions and to evaluate their potential effects on preterm infants.
Topics: Fat Emulsions, Intravenous; Fatty Acids, Nonesterified; Female; Humans; In Vitro Techniques; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infant, Premature; Male; Oxylipins; Parenteral Nutrition
PubMed: 31058781
DOI: 10.1097/MPG.0000000000002369 -
Phytomedicine : International Journal... Sep 2021Salvianolic acids have a special synergic effect on panax notoginsenosides in acute myocardial infarction (AMI) and have been developed into a new drug as Danqi Tongmai...
Salvianolic acids have a special synergic effect on panax notoginsenosides in acute myocardial infarction (AMI) and have been developed into a new drug as Danqi Tongmai Tablet (DQTT). To explore candidate targets and mechanisms of DQTT on AMI, a network pharmacology-based analysis was performed on absorbed prototype compounds of DQTT in rat plasma. Target prediction from network analysis indicated that the arachidonic acid pathway might contribute to the therapeutic effects of DQTT on AMI, and the regulatory effects on cyclooxygenase (COX) and lipoxygenase (LOX) were validated using an oxygen-glucose deprivation/reoxygenation model established on H9c2 cardiomyocytes. To further explore the action mechanisms of DQTT, 38 oxylipins were quantitatively analyzed among high, medium, and low doses of DQTT using a rat AMI model with an ultra high performance liquid chromatograph coupled with a triple quadrupole mass spectrometry (UHPLC-QqQ/MS) detection system. As attenuation was observed in AMI with DQTT treatment, the perturbed arachidonic acid metabolome was partly restored in a dose-dependent fashion with a significant elevation of anti-inflammatory metabolites, while pro-inflammatory lipids were decreased. Cytokine array analysis also supported the anti-inflammatory effects of DQTT, as significant down-regulation of pro-inflammatory cytokines was observed. The analysis of ischemic heart tissues demonstrated that COX and LOX, the inflammation-induced catalytic enzymes of arachidonic acid metabolism, were inhibited on both gene expression and protein level. These results confirmed that DQTT could restore the arachidonic acid metabolome to maintain an anti-inflammatory profile against the ischemic tissue injury and support that DQTT can be a promising medicinal therapy against AMI.
Topics: Animals; Cell Line; Drugs, Chinese Herbal; Myocardial Infarction; Myocytes, Cardiac; Oxylipins; Rats; Tablets
PubMed: 34252738
DOI: 10.1016/j.phymed.2021.153616 -
Lipids Nov 2020Human milk contains oxylipins involved in infant development. Although oxylipins have been identified in whole or skim milk, their localization within human milk cream,...
Human milk contains oxylipins involved in infant development. Although oxylipins have been identified in whole or skim milk, their localization within human milk cream, cell, and skim fractions is not known. This study determined the distribution of free and esterified oxylipins in cream, cell, and skim fractions of human milk. Out of 72 oxylipins probed by mass-spectrometry, 42, 29, and 41 oxylipins (free or bound) were detected in cream, cell, and skim fractions, respectively. Over 90% of free and bound oxylipins were derived from linoleic acid in all milk fractions. Other oxylipins were derived from n-6 arachidonic acid and dihomo-gamma-linolenic acid, and n-3 alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid. Free oxylipins were more abundant in skim milk (59.9% of total oxylipins) compared to cream and cell pellet, whereas esterified oxylipins were most abundant in milk cream and cell pellets (74.9-76.9%). The heterogenous distribution of oxylipins in different fractions of human milk may regulate the guided release of these bioactive signaling molecules within infants.
Topics: Chromatography, High Pressure Liquid; Esterification; Female; Humans; Linoleic Acid; Milk, Human; Oxylipins; Tandem Mass Spectrometry
PubMed: 32725684
DOI: 10.1002/lipd.12268 -
Journal of Agricultural and Food... Dec 2022Oxylipins play important signaling roles in aflatoxin (AF) biosynthesis in . We previously showed that exogenous supply of autoxidated linolenic acid (AL) inhibited AF...
Oxylipins play important signaling roles in aflatoxin (AF) biosynthesis in . We previously showed that exogenous supply of autoxidated linolenic acid (AL) inhibited AF biosynthesis in via oxylipins, but the molecular mechanism is still unknown. Here, we performed multiomics analyses of grown in media with or without AL. Targeted metabolite analyses and quantitative reverse transcription (qRT)-polymerase chain reaction (PCR) showed that the imizoquin (IMQ) biosynthetic pathway was distinctly upregulated in the presence of AL. C-glucose labeling confirmed in parallel that the tricarboxylic acid cycle was also enhanced by AL, consistent with observed increases in mycelial growth. Moreover, we integrated thermal proteome profiling and molecular dynamics simulations to identify a potential receptor of AL; AL was found to interact with a transporter (ImqJ) located in the IMQ gene cluster, primarily through hydrophobic interactions. Further analyses of strains with an IMQ pathway transcription factor overexpressed or knocked out confirmed that this pathway was critical for AL-mediated inhibition of AF biosynthesis. Comparison of 22 assembled and genomes showed that genes involved in the IMQ pathway were positively selected in . Taken together, the results of our study provide novel insights into oxylipin-mediated regulation of AF biosynthesis and suggest potential methods for preventing AF contamination of crops.
Topics: Aspergillus flavus; Oxylipins; Aflatoxins; alpha-Linolenic Acid; Transcription Factors
PubMed: 36508213
DOI: 10.1021/acs.jafc.2c06230 -
Marine Drugs Dec 2018Algicidal bacteria can lyse microalgal blooms and trigger shifts within plankton communities. Resistant algal species can escape lysis, and have the opportunity to...
Algicidal bacteria can lyse microalgal blooms and trigger shifts within plankton communities. Resistant algal species can escape lysis, and have the opportunity to dominate the phytoplankton after a bacterial infection. Despite their important function in ecosystem regulation, little is known about mechanisms of resistance. Here, we show that the diatom releases eicosanoid oxylipins into the medium, and that the lytic algicidal bacterium, , induces the production of several wound-activated oxylipins in this resistant diatom. Neither releases nor an induction occurs in the susceptible diatom that is lysed by the bacterium within a few days. Among the upregulated oxylipins, hydroxylated eicosapentaenoic acids (HEPEs) dominate. However, also, resolvins, known lipid mediators in mammals, increase upon exposure of the algae to the algicidal bacteria. The prevailing hydroxylated fatty acid, 15-HEPE, significantly inhibits growth of at a concentration of approximately 1 µM. The oxylipin production may represent an independent line of defense of the resistant alga, acting in addition to the previously reported upregulation of proteases.
Topics: Diatoms; Ecosystem; Eutrophication; Flavobacteriaceae; Microalgae; Oxylipins; Water Microbiology
PubMed: 30518148
DOI: 10.3390/md16120486 -
Pediatric Research Nov 2022Oxylipins are metabolites derived from fatty acids such as arachidonic acid (AA) and are key mediators in inflammation, host defense, and tissue injury. Serum oxylipins...
BACKGROUND
Oxylipins are metabolites derived from fatty acids such as arachidonic acid (AA) and are key mediators in inflammation, host defense, and tissue injury. Serum oxylipins increase in adults after cardiopulmonary bypass (CPB) but tissue-level changes are poorly defined. The objective of this study was to characterize pulmonary tissue oxylipins in an infant porcine model of CPB with deep hypothermic circulatory arrest (DHCA).
METHODS
Infant pigs underwent CPB with DHCA. Controls received anesthesia only. Right upper and lower lobes of the lung underwent oxylipin analysis via liquid chromatography-tandem mass spectrometry. One-way ANOVA was utilized to assess differences in oxylipin concentrations across groups, followed by pairwise comparisons.
RESULTS
AA and multiple AA metabolites via cytochrome P450 (CYP450), lipoxygenase (LOX), and cyclooxygenase (COX) pathways were significantly increased in the upper and lower lobe of pigs exposed to CPB/DHCA as compared to controls. Multiple prostaglandin metabolites produced via COX were also significantly elevated in the lower lobes of control animals.
CONCLUSIONS
CPB/DHCA induces a significant increase in pulmonary tissue AA, with subsequent metabolism via COX, LOX, and CYP450 pathways. Interestingly, prostaglandins were also elevated in the lower lobes of the controls, suggesting a mechanism separate from CPB/DHCA. Future oxylipin studies are needed to better understand CPB-induced acute lung injury.
IMPACT
CPB/DHCA and, to a lesser extent, lung region influence pulmonary tissue-level AA metabolite production. Inflammatory mediator AA metabolites have been noted in previous studies to increase following CPB; however, this is the first study to look at pulmonary tissue-level differences following CPB/DHCA. Increases in many AA metabolites, including LOX- and CYP450-derived products, were seen in both upper and lower lobe of piglets following CPB/DHCA. COX-derived prostaglandin metabolites were increased not only in CPB upper and lower lobe but also in mechanically ventilated control lower lobe, suggesting an additional, separate mechanism from CPB/DCHA.
Topics: Animals; Swine; Cardiopulmonary Bypass; Oxylipins; Lung; Inflammation; Prostaglandins
PubMed: 35681098
DOI: 10.1038/s41390-022-02125-5