14,17,18-Trihydroxy-Eicosatetraenoic Acid: A Novel Pro-Resolving Lipid Mediator from Marine Microalgae

Author(s):  
Hans Jagusch ◽  
Markus Werner ◽  
Duco Koenis ◽  
Jesmond Dalli ◽  
Oliver Werz ◽  
...  

2021 ◽  
Vol 22 (17) ◽  
pp. 9295
Author(s):  
Shinya Takenouchi ◽  
Daiki Imai ◽  
Tatsuro Nakamura ◽  
Takahisa Murata

5,6-dihydroxy-8Z,11Z,14Z,17Z-eicosatetraenoic acid (5,6-DiHETE) is an eicosapentaenoic acid-derived newly discovered bioactive anti-inflammatory lipid mediator having diverse functions. Here, we assessed the potential of orally administered 5,6-DiHETE in promoting healing of dextran sulfate sodium (DSS)-induced colitis in mice. We measured the plasma concentrations of 5,6-DiHETE in untreated mice before and 0.5, 1, 3, and 6 h after its oral administration (150 or 600 μg/kg) in mice. Mice developed colitis by DSS (2% in drinking water for 4 days), and 5,6-DiHETE (150 or 600 μg/kg/day) was orally administered from day 9 to 14. Next, the faecal hardness and bleeding were assessed, and the dissected colons on day 14 via H&E staining. The plasma concentration of 5,6-DiHETE reached 25.05 or 44.79 ng/mL 0.5 h after the administration of 150 or 600 μg/kg, respectively, followed by a gradual decrease. The half-life of 5,6-DiHETE was estimated to be 1.25–1.63 h. Diarrhoea deteriorated after day 3 and peaked on day 5, followed by a gradual recovery. Histological assessment on day 14 showed DSS-mediated granulocyte infiltration, mucosal erosion, submucosal edema, and cryptal abscesses in mice. Oral administration of 150 or 600 μg/kg/day of 5,6-DiHETE accelerated the recovery from the DSS-induced diarrhoea and significantly ameliorated colon inflammation. The therapeutic effect of 600 μg/kg/day 5,6-DiHETE was slightly stronger than that by 150 μg/kg/day. Our study reveals attenuation of DSS-induced colitis in mice by the oral administration of 5,6-DiHETE dose-dependently, thereby suggesting a therapeutic potential of 5,6-DiHETE for inflammatory bowel disease.



1981 ◽  
Vol 153 (2) ◽  
pp. 482-487 ◽  
Author(s):  
E J Goetzl ◽  
W C Pickett

A specific 5(S),12(R)-dihydroxy-eicosa-6,8,10(trans/trans/cis), 14(cis)-tetraenoic acid, designated leukotriene B, is generated by the lipoxygenation and subsequent enzymatic hydration of arachidonic acid in a variety of leukocytes. Leukotriene B elicits a maximal human neutrophil chemotactic response in vitro which is similar in magnitude to those evoked by the chemotactic fragment of the fifth component of complement, C5a, synthetic formyl-methionyl peptides, and 5-hydroxy-eicosatetraenoic acid (5-HETE). The neutrophil chemotactic potency of purified leukotriene B, assessed by the 50% effective concentration of 6 x 10(-9) M, is equivalent to that of C5a, but is up to 100-fold greater than that of 5-HETE and of other natural di-HETE isomers. 5(S),12(R)-di-hydroxy-eicosa-6,8,10(all-trans),14(cis)-tetraenoic acid, which differs from leukotriene B only in having a trans-double bond in place of a cis-double bond in the triene portion of the molecule, and acetyl-leukotriene B are significantly less potent neutrophil chemotactic factors than leukotriene B, which indicates that both the conjugated double bonds and the free hydroxyl-group(s) are functionally critical determinants. The capacity of acetyl-leukotriene B to inhibit competitively and selectively the human neutrophil chemotactic response to equimolar concentrations of leukotriene B suggests the existence of a specific subset of receptors for this potent lipid mediator.



2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
L Rotheudt ◽  
E Moritz ◽  
M Markus ◽  
H Voelzke ◽  
N Friedrich ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Introduction  Sphingosine-1-phosphate (S1P) is a lipid mediator of the immune system and vascular bed. However, cross-sectional analyses of S1P and parameters of vascular health in the population are sparse. Purpose  We explored the relation between S1P concentrations and several parameters of vascular health, i.e. ankle-brachial index (ABI), carotid intima-media thickness (cIMT), presence of carotid atherosclerotic plaques/stenosis, brachial artery flow-mediated dilation (FMD) as well as aortic wall thickness (AWT). Methods S1P was measured by liquid chromatography-tandem mass spectrometry in the population-based Study of Health in Pomerania (SHIP-TREND-0). ABI was calculated as the ratio of systolic blood pressure in arms and ankles. For cIMT, the distance between the lumen-intima and media-adventitia interfaces in longitudinal scans were measured. Carotid plaques were defined as a focal protrusion of the carotid vessel wall. Carotid stenosis was assessed with Doppler ultrasonography. FMD was evaluated by measuring the increase in brachial artery diameter after transient forearm ischemia. AWT was assessed by Magnetic Resonance Imaging.  Subjects with cancer, severe renal insufficiency, previous myocardial infarction and extreme values for S1P (< 1st and > 99th percentile) were excluded. Sex stratified linear regression models adjusted for age, smoking, waist-to-hip ratio and platelets were used to assess the relation between S1P and vascular disease parameters. Results A total of n = 3,643 participants (48% male, median age 51, 25th and 75th percentile 39 and 63 years) could be included in the analyses. The median S1P concentration was 0.788 µM (25th and 75th percentile 0.679 and 0.906, respectively). In men a 1 standard deviation higher S1P was associated with a significantly greater cIMT (β: 0.0057 95% confidence interval [CI]: 0.00027 to 0.0112 mm; p = 0.0396) and a lower ABI (β: -0.0090 (95% confidence interval [CI]: -0.0153 to -0.0029; p = 0.0038. In women S1P was significantly associated with cIMT (β: 0.0044 95% confidence interval [CI]: 0.0001 to 0.0086 mm; p = 0.0445) while no significant association was found for the relation of S1P with ABI. For both men and women S1P was not associated with FMD, the presence of carotid plaques/stenosis and AWT. Conclusions We found that S1P concentrations were positively related to a thicker cIMT in both sexes and lower ABI values in men. There was no association of S1P with any of the other vascular markers of interest. Future studies need to validate our results in other populations.



Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 801
Author(s):  
Maria Detopoulou ◽  
Agathi Ntzouvani ◽  
Filio Petsini ◽  
Labrini Gavriil ◽  
Εlizabeth Fragopoulou ◽  
...  

Platelet-activating factor (PAF), a proinflammatory lipid mediator, plays a crucial role in the formation of the atherosclerotic plaque. Therefore, the inhibition of endothelium inflammation by nutraceuticals, such as PAF inhibitors, is a promising alternative for preventing cardiovascular diseases. The aim of the present study was to evaluate the impact of a new functional yogurt enriched with PAF inhibitors of natural origin from olive oil by-products on PAF metabolism. Ninety-two apparently healthy, but mainly overweight volunteers (35–65 years) were randomly allocated into three groups by block-randomization. The activities of PAF’s biosynthetic and catabolic enzymes were measured, specifically two isoforms of acetyl-CoA:lyso-PAF acetyltransferase (LPCATs), cytidine 5′-diphospho-choline:1-alkyl-2-acetyl-sn-glycerol cholinephosphotransferase (PAF-CPT) and two isoforms of platelet activating factor acetylhydrolase in leucocytes (PAF-AH) and plasma (lipoprotein associated phospholipase-A2, LpPLA2). The intake of the enriched yogurt resulted in reduced PAF-CPT and LpPLA2 activities. No difference was observed in the activities of the two isoforms of lyso PAF-AT. In conclusion, intake of yogurt enriched in PAF inhibitors could favorably modulate PAF biosynthetic and catabolic pathways.



Chemosphere ◽  
2021 ◽  
pp. 130775
Author(s):  
Isadora Machado Marques ◽  
Adna Caroline Vale Oliveira ◽  
Olivia Maria Cordeiro de Oliveira ◽  
Emerson Andrade Sales ◽  
Ícaro Thiago Andrade Moreira


1993 ◽  
Vol 34 (4) ◽  
pp. 625-631
Author(s):  
J Wigren ◽  
H Herbertsson ◽  
O Tollbom ◽  
S Hammarström


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