scholarly journals Chlorinated Phospholipids and Fatty Acids: (Patho)physiological Relevance, Potential Toxicity, and Analysis of Lipid Chlorohydrins

2016 ◽  
Vol 2016 ◽  
pp. 1-26 ◽  
Author(s):  
Jenny Schröter ◽  
Jürgen Schiller
Keyword(s):  
Fatty Acids ◽  
Hypochlorous Acid ◽  
Inflammatory Diseases ◽  
Fatty Acyl ◽  
Head Group ◽  
Inflammatory Conditions ◽  
First Case ◽  
Physiological Relevance ◽  
Fatty Aldehydes

Chlorinated phospholipids are formed by the reaction of hypochlorous acid (HOCl), generated by the enzyme myeloperoxidase under inflammatory conditions, and the unsaturated fatty acyl residues or the head group. In the first case the generated chlorohydrins are both proinflammatory and cytotoxic, thus having a significant impact on the structures of biomembranes. The latter case leads to chloramines, the properties of which are by far less well understood. Since HOCl is also widely used as a disinfecting and antibacterial agent in medicinal, industrial, and domestic applications, it may represent an additional source of danger in the case of abuse or mishandling. This review discusses the reaction behavior of in vivo generated HOCl and biomolecules like DNA, proteins, and carbohydrates but will focus on phospholipids. Not only the beneficial and pathological (toxic) effects of chlorinated lipids but also the importance of these chlorinated species is discussed. Some selected cleavage products of (chlorinated) phospholipids and plasmalogens such as lysophospholipids, (chlorinated) free fatty acids andα-chloro fatty aldehydes, which are all well known to massively contribute to inflammatory diseases associated with oxidative stress, will be also discussed. Finally, common analytical methods to study these compounds will be reviewed with focus on mass spectrometric techniques.

scholarly journals Effect of long-chain fatty acyl-CoA on mitochondrial and cytosolic ATP/ADP ratios in the intact liver cell

1984 ◽  
Vol 220 (2) ◽  
pp. 371-376 ◽  
Author(s):  
S Soboll ◽  
H J Seitz ◽  
H Sies ◽  
B Ziegler ◽  
R Scholz
Keyword(s):  
Liver Cell ◽  
Adenine Nucleotide ◽  
Intact Cell ◽  
Inhibitory Effect ◽  
Fatty Acyl ◽  
Fed State ◽  
Physiological Relevance ◽  
Chain Acyl ◽  
Long Chain

The effect of long-chain acyl-CoA on subcellular adenine nucleotide systems was studied in the intact liver cell. Long-chain acyl-CoA content was varied by varying the nutritional state (fed and starved states) or by addition of oleate. Starvation led to an increase in the mitochondrial and a decrease in the cytosolic ATP/ADP ratio in liver both in vivo and in the isolated perfused organ as compared with the fed state. The changes were reversed on re-feeding glucose in liver in vivo or on infusion of substrates (glucose, glycerol) in the perfused liver, respectively. Similar changes in mitochondrial and cytosolic ATP/ADP ratios occurred on addition of oleate, but, importantly, not with a short-chain fatty acid such as octanoate. It is concluded that long-chain acyl-CoA exerts an inhibitory effect on mitochondrial adenine nucleotide translocation in the intact cell, as was previously postulated in the literature from data obtained with isolated mitochondria. The physiological relevance with respect to pyruvate metabolism, i.e. regulation of pyruvate carboxylase and pyruvate dehydrogenase by the mitochondrial ATP/ADP ratio, is discussed.

scholarly journals Σύνθεση και μελέτη αναστολέων λιπολυτικών ενζύμων

2016 ◽  
Author(s):  
Αικατερίνη Νικολάου
Keyword(s):  
Fatty Acids ◽  
Lysophosphatidic Acid ◽  
Inhibitory Activity ◽  
Functional Group ◽  
Inflammatory Diseases ◽  
Hydroxamic Acids ◽  
Pharmacological Properties ◽  
Ester Bond ◽  
Phospholipases A2 ◽  
Inflammatory Conditions

Phospholipases A2 (PLA2) are enzymes that hydrolyze the sn-2 ester bond of phospholipids releasing free fatty acids and lysophospholipids. Among them, arachidonic acid can be converted into a variety of eicosanoids by metabolic enzymes, while lysophosphatidylcholine (LPC), the most abundant lysophospholipid in plasma and tissues, can be converted into lysophosphatidic acid (LPA) by a secreted enzyme that exhibits lysophospholipase D activity, known as autotaxin (ATX). Both enzymes are involved in inflammatory conditions and, as a consequence, constitute attractive targets for the development of novel agents for the treatment of inflammatory diseases. Due to the fact that molecules which bear the 2-oxoamide functional group and long aliphatic chains exhibit inhibitory activity against cytosolic GIVA cPLA2, 2-oxoamideswith reduced lipophilicity were designed and synthesized. Taking into consideration that in recent years hydroxamic acids have attracted considerable attention due to their pharmacological properties, hydroxamic acids and derivatives there of were designed and synthesized, so as to evaluate their inhibitory activity against ATX.

scholarly journals The effects of 5-hydroxytryptophan on carrageenan-induced mouse paw oedemas

2021 ◽  
Vol 34 ◽  
Author(s):  
Gokçen TELLI ◽  
Inci KAZKAYASI ◽  
Serdar UMA
Keyword(s):  
Oral Absorption ◽  
Inflammatory Diseases ◽  
Food Supplement ◽  
Peripheral Inflammation ◽  
Independent Manner ◽  
Inflammatory Conditions ◽  
Paw Oedema ◽  
Serotonin Biosynthesis ◽  
Oral Doses

ABSTRACT Objective 5-Hydroxytryptophan is the precursor compound of serotonin biosynthesis. The oral absorption of 5-Hydroxytryptophan is close to 100% and, unlike serotonin, it crosses the blood-brain barrier freely. 5-Hydroxytryptophan has been used as a food supplement for many years to treat anxiety and depression. Recent studies have shown that 5-Hydroxytryptophan suppresses the pro-inflammatory mediators and is effective in some inflammatory diseases, such as arthritis and allergic asthma. However, the role of 5-Hydroxytryptophan supplements on acute peripheral inflammation has not been investigated yet. In this study, the in vivo anti-inflammatory activity of 5-Hydroxytryptophan was evaluated with a carrageenan-induced paw oedema test in mice. Methods For the investigation of the acute antiinflammatory activity, single oral doses of 5-Hydroxytryptophan (1.5, 5 and 20mg/kg) were given to mice 1.5 hours prior to the carrageenan test. For chronic activity, the same oral doses were administered daily for two weeks prior to the carrageenan test on the 14th day. To induce inflammation, 0.01mL of 2% carrageenan was injected into the paws of mice. Results Supplementation with 5-Hydroxytryptophan significantly reduced inflammation in a dose-independent manner which was irrespective of the duration of exposure (per cent inhibition in acute experiments was 35.4%, 20.9%, 24.0%, and per cent inhibition in chronic experiments was 29.5%, 35.3%, 40.8% for the doses of 1.5, 5, and 20mg/kg, respectively). Conclusion Our findings demonstrate for the first time that 5-HTP supplements have the potential of suppressing the measures of acute peripheral inflammation. It is suggested that, apart from several diseases where serotonin is believed to play an important role, including depression, patients with inflammatory conditions may also benefit from 5-HTP.

Oxidized omega-3 fatty acids in fish oil inhibit leukocyte-endothelial interactions through activation of PPARα

Blood ◽  
2002 ◽  
Vol 100 (4) ◽  
pp. 1340-1346 ◽  
Author(s):  
Sanjeev Sethi ◽  
Ouliana Ziouzenkova ◽  
Heyu Ni ◽  
Denisa D. Wagner ◽  
Jorge Plutzky ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fish Oil ◽  
Inflammatory Diseases ◽  
Receptor Expression ◽  
Peroxisome Proliferator ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Peroxisome Proliferator Activated Receptor

Omega-3 fatty acids, which are abundant in fish oil, improve the prognosis of several chronic inflammatory diseases although the mechanism for such effects remains unclear. These fatty acids, such as eicosapentaenoic acid (EPA), are highly polyunsaturated and readily undergo oxidation. We show that oxidized, but not native unoxidized, EPA significantly inhibited human neutrophil and monocyte adhesion to endothelial cells in vitro by inhibiting endothelial adhesion receptor expression. In transcriptional coactivation assays, oxidized EPA potently activated the peroxisome proliferator-activated receptor α (PPARα), a member of the nuclear receptor family. In vivo, oxidized, but not native, EPA markedly reduced leukocyte rolling and adhesion to venular endothelium of lipopolysaccharide (LPS)–treated mice. This occurred via a PPARα-dependent mechanism because oxidized EPA had no such effect in LPS-treated PPARα-deficient mice. Therefore, the beneficial effects of omega-3 fatty acids may be explained by a PPARα-mediated anti-inflammatory effect of oxidized EPA.

scholarly journals Acute induction of anomalous and amyloidogenic blood clotting by molecular amplification of highly substoichiometric levels of bacterial lipopolysaccharide

2016 ◽  
Vol 13 (122) ◽  
pp. 20160539 ◽  
Author(s):  
Etheresia Pretorius ◽  
Sthembile Mbotwe ◽  
Janette Bester ◽  
Christopher J. Robinson ◽  
Douglas B. Kell
Keyword(s):  
Inflammatory Diseases ◽  
Isothermal Calorimetry ◽  
Amyloid Β ◽  
Bacterial Lipopolysaccharide ◽  
Primary Role ◽  
Inflammatory Conditions ◽  
Healthy Donors ◽  
Mechanistic Analysis ◽  
Amyloid Diseases

It is well known that a variety of inflammatory diseases are accompanied by hypercoagulability, and a number of more-or-less longer-term signalling pathways have been shown to be involved. In recent work, we have suggested a direct and primary role for bacterial lipopolysaccharide (LPS) in this hypercoagulability, but it seems never to have been tested directly. Here, we show that the addition of tiny concentrations (0.2 ng l −1 ) of bacterial LPS to both whole blood and platelet-poor plasma of normal, healthy donors leads to marked changes in the nature of the fibrin fibres so formed, as observed by ultrastructural and fluorescence microscopy (the latter implying that the fibrin is actually in an amyloid β-sheet-rich form that on stoichiometric grounds must occur autocatalytically). They resemble those seen in a number of inflammatory (and also amyloid) diseases, consistent with an involvement of LPS in their aetiology. These changes are mirrored by changes in their viscoelastic properties as measured by thromboelastography. As the terminal stages of coagulation involve the polymerization of fibrinogen into fibrin fibres, we tested whether LPS would bind to fibrinogen directly. We demonstrated this using isothermal calorimetry. Finally, we show that these changes in fibre structure are mirrored when the experiment is done simply with purified fibrinogen and thrombin (±0.2 ng l −1 LPS). This ratio of concentrations of LPS : fibrinogen in vivo represents a molecular amplification by the LPS of more than 10 8 -fold, a number that is probably unparalleled in biology. The observation of a direct effect of such highly substoichiometric amounts of LPS on both fibrinogen and coagulation can account for the role of very small numbers of dormant bacteria in disease progression in a great many inflammatory conditions, and opens up this process to further mechanistic analysis and possible treatment.

Potent and selective 2-oxoamide inhibitors of phospholipases A2 as novel medicinal agents for the treatment of inflammatory diseases

2012 ◽  
Vol 84 (9) ◽  
pp. 1877-1894 ◽  
Author(s):  
Efrosini Barbayianni ◽  
Georgia Antonopoulou ◽  
George Kokotos
Keyword(s):  
Amino Acids ◽  
Fatty Acids ◽  
Inflammatory Diseases ◽  
Ester Bond ◽  
Selective Inhibitors ◽  
Phospholipases A2 ◽  
Hydrolysis Of ◽  
Major Target ◽  
Phospholipases A

Phospholipases A2 (PLA2s) are enzymes that are capable of catalyzing the hydrolysis of the sn-2 ester bond of glycerophospholipids, releasing free fatty acids, including arachidonic acid (AA), and lysophospholipids. Both products are precursor signaling molecules involved in inflammation. Among the various PLA2s, cytosolic GIVA cPLA2 is considered a major target for inflammatory diseases, while secreted GIIA sPLA2 is involved in cardiovascular diseases. We have developed lipophilic 2-oxoamides based on (S)-γ- or δ-amino acids as potent and selective inhibitors of GIVA cPLA2, which present interesting in vivo anti-inflammatory activity. 2-Oxoamides based on natural α-amino acids are selective inhibitors of GIIA sPLA2. The mode of binding of 2-oxoamides with either GIVA cPLA2 or GIIA sPLA2 has been studied by various techniques.

scholarly journals Peptide inhibition of neutrophil-mediated injury after in vivo challenge with supernatant of Pseudomonas aeruginosa and immune-complexes

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254353
Author(s):  
Adrianne Enos ◽  
Parvathi Kumar ◽  
Brittany Lassiter ◽  
Alana Sampson ◽  
Pamela Hair ◽  
...  
Keyword(s):  
Immune Complexes ◽  
Hypochlorous Acid ◽  
Inflammatory Diseases ◽  
Fold Increase ◽  
Neutrophil Extracellular Trap ◽  
Myeloperoxidase Activity ◽  
Free Dna ◽  
Dna 2

Neutrophils are recognized for their role in host defense against pathogens as well as inflammatory conditions mediated through many mechanisms including neutrophil extracellular trap (NET) formation and generation of reactive oxygen species (ROS). NETs are increasingly appreciated as a major contributor in autoimmune and inflammatory diseases such as cystic fibrosis. Myeloperoxidase (MPO), a key neutrophil granule enzyme mediates generation of hypochlorous acid which, when extracellular, can cause host tissue damage. To better understand the role played by neutrophils in inflammatory diseases, we measured and modulated myeloperoxidase activity and NETs in vivo, utilizing a rat peritonitis model. RLS-0071 is a 15 amino acid peptide that has been shown to inhibit myeloperoxidase activity and NET formation in vitro. The rat model of inflammatory peritonitis was induced with intraperitoneal injection of either P. aeruginosa supernatant or immune-complexes. After euthanasia, a peritoneal wash was performed and measured for myeloperoxidase activity and free DNA as a surrogate for measurement of NETs. P. aeruginosa supernatant caused a 2-fold increase in MPO activity and free DNA when injected IP. Immune-complexes injected IP increased myeloperoxidase activity and free DNA 2- fold. RLS-0071 injection decreased myeloperoxidase activity and NETs in the peritoneal fluid generally to baseline levels in the presence of P. aeruginosa supernatant or immune-complexes. Taken together, RLS-0071 demonstrated the ability to inhibit myeloperoxidase activity and NET formation in vivo when initiated by different inflammatory stimuli including shed or secreted bacterial constituents as well as immune-complexes.

scholarly journals A transgenic zebrafish line for in vivo visualisation of neutrophil myeloperoxidase

2018 ◽  
Author(s):  
Kyle D. Buchan ◽  
Tomasz K. Prajsnar ◽  
Nikolay V. Ogryzko ◽  
Nienke W.M. de Jong ◽  
Michiel van Gent ◽  
...  
Keyword(s):  
Hypochlorous Acid ◽  
Neutrophil Migration ◽  
Subcellular Location ◽  
Human Neutrophils ◽  
Transgenic Zebrafish ◽  
Inflammatory Conditions ◽  
Granular Dynamics ◽  
Increased Risk ◽  
Potential Applications

AbstractThe neutrophil enzyme myeloperoxidase (MPO) is a major enzyme made by neutrophils to generate antimicrobial and immunomodulatory compounds, notably hypochlorous acid (HOCl), amplifying their capacity for destroying pathogens and regulating inflammation. Despite its roles in innate immunity, the importance of MPO in preventing infection is unclear, as individuals with MPO deficiency are asymptomatic with the exception of an increased risk of candidiasis. Dysregulation of MPO activity is also linked with inflammatory conditions such as atherosclerosis, emphasising a need to understand the roles of the enzyme in greater detail. Consequently, new tools for investigating granular dynamics in vivo can provide useful insights into how MPO localises within neutrophils, aiding understanding of its role in preventing and exacerbating disease. The zebrafish is a powerful model for investigating the immune system in vivo, as it is genetically tractable, and optically transparent.To visualise MPO activity within zebrafish neutrophils, we created a genetic construct that expresses human MPO as a fusion protein with a C-terminal fluorescent tag, driven by the neutrophil-specific promoter lyz. After introducing the construct into the zebrafish genome by Tol2 transgenesis, we established the Tg(lyz:Hsa.MPO-mEmerald,cmlc2:EGFP)sh496 line, and confirmed transgene expression in zebrafish neutrophils. We observed localisation of MPO-mEmerald within a subcellular location resembling neutrophil granules, mirroring MPO in human neutrophils. In Spotless (mpxNL144) larvae - which express a non-functional zebrafish myeloperoxidase - the MPO-mEmerald transgene does not disrupt neutrophil migration to sites of infection or inflammation, suggesting that it is a suitable line for the study of neutrophil granule function.We present a new transgenic line that can be used to investigate neutrophil granule dynamics in vivo without disrupting neutrophil behaviour, with potential applications in studying processing and maturation of MPO during development.

scholarly journals Essential Oils and Their Major Compounds in the Treatment of Chronic Inflammation: A Review of Antioxidant Potential in Preclinical Studies and Molecular Mechanisms

2018 ◽  
Vol 2018 ◽  
pp. 1-23 ◽  
Author(s):  
Érica Martins de Lavor ◽  
Antônio Wilton Cavalcante Fernandes ◽  
Roxana Braga de Andrade Teles ◽  
Ana Ediléia Barbosa Pereira Leal ◽  
Raimundo Gonçalves de Oliveira Júnior ◽  
...  
Keyword(s):  
Essential Oils ◽  
Chronic Inflammation ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Biologically Active ◽  
Preclinical Studies ◽  
Inflammatory Conditions ◽  
Potential Activity

Inflammatory diseases result from the body’s response to tissue damage, and if the resolution is not adequate or the stimulus persists, there will be progression from acute inflammation to chronic inflammation, leading to the development of cancer and neurodegenerative and autoimmune diseases. Due to the complexity of events that occur in inflammation associated with the adverse effects of drugs used in clinical practice, it is necessary to search for new biologically active compounds with anti-inflammatory activity. Among natural products, essential oils (EOs) present promising results in preclinical studies, with action in the main mechanisms involved in the pathology of inflammation. The present systematic review summarizes the pharmacological effects of EOs and their compounds in in vitro and in vivo models for inflammation. The research was conducted in the following databases: PubMed, Scopus, BIREME, Scielo, Open Grey, and Science Direct. Based on the inclusion criteria, 30 articles were selected and discussed in this review. The studies listed revealed a potential activity of EOs and their compounds for the treatment of inflammatory diseases, especially in chronic inflammatory conditions, with the main mechanism involving reduction of reactive oxygen and nitrogen species associated with an elevation of antioxidant enzymes as well as the reduction of the nuclear factor kappa B (NF-κB), reducing the expression of proinflammatory cytokines. Thus, this review suggests that EOs and their major compounds are promising tools for the treatment of chronic inflammation.

scholarly journals Therapeutic Role of miR-30a in Lipoteichoic Acid-Induced Endometritis via Targeting the MyD88/Nox2/ROS Signaling

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Kangfeng Jiang ◽  
Weiqi Ye ◽  
Qian Bai ◽  
Jinyin Cai ◽  
Haichong Wu ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Lipoteichoic Acid ◽  
In Vivo Studies ◽  
Economic Losses ◽  
Inflammatory Conditions ◽  
Wide Range

Staphylococcus aureus (S. aureus), a notorious pathogenic bacterium prevalent in the environment, causes a wide range of inflammatory diseases such as endometritis. Endometritis is an inflammatory disease in humans and mammals, which prolongs uterine involution and causes great economic losses. MiR-30a plays an importan trole in the process of inflammation; however, the regulatory role of miR-30a in endometritis is still unknown. Here, we first noticed that there was an increased level of miR-30a in uterine samples of cows with endometritis. And then, bovine endometrial epithelial (BEND) cells stimulated with the virulence factor lipoteichoic acid (LTA) from S. aureus were used as an in vitro endometritis model to explore the potential role of miR-30a in the pathogenesis of endometritis. Our data showed that the induction of the miR-30a expression is dependent on NF-κB activation, and its overexpression significantly decreased the levels of IL-1β and IL-6. Furthermore, we observed that the overexpression of miR-30a inhibited its translation by binding to 3 ′ − UTR of MyD88 mRNA, thus preventing the activation of Nox2 and NF-κB and ROS accumulation. Meanwhile, in vivo studies further revealed that upregulation of miR-30a using chemically synthesized agomirs alleviates the inflammatory conditions in an experimental mouse model of endometritis, as indicated by inhibition of ROS and NF-κB. Taken together, these findings highlight that miR-30a can attenuate LTA-elicited oxidative stress and inflammatory responses through the MyD88/Nox2/ROS/NF-κB pathway and may aid the future development of novel therapies for inflammatory diseases caused by S. aureus, including endometritis.

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