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https://www.readbyqxmd.com/read/29238213/first-evidence-of-the-conversion-of-paracetamol-to-am404-in-human-cerebrospinal-fluid
#1
Chhaya V Sharma, Jamie H Long, Seema Shah, Junia Rahman, David Perrett, Samir S Ayoub, Vivek Mehta
Paracetamol is arguably the most commonly used analgesic and antipyretic drug worldwide, however its mechanism of action is still not fully established. It has been shown to exert effects through multiple pathways, some actions suggested to be mediated via N-arachidonoylphenolamine (AM404). AM404, formed through conjugation of paracetamol-derived p-aminophenol with arachidonic acid in the brain, is an activator of the capsaicin receptor, TRPV1, and inhibits the reuptake of the endocannabinoid, anandamide, into postsynaptic neurons, as well as inhibiting synthesis of PGE2 by COX-2...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/29237716/shared-and-distinct-lipid-lipid-interactions-in-plasma-and-affected-tissues-in-a-diabetic-mouse-model
#2
Kelli M Sas, Jiahe Lin, Thekkelnaycke M Rajendiran, Tanu Soni, Viji Nair, Lucy M Hinder, Hosagrahar V Jagadish, Thomas W Gardner, Steven F Abcouwer, Frank C Brosius, Eva L Feldman, Matthias Kretzler, George Michailidis, Subramaniam Pennathur
Lipids are ubiquitous metabolites with diverse functions; abnormalities in lipid metabolism appear related to complications from multiple diseases, including type 2 diabetes. Through technological advances, the entire lipidome has been characterized, and researchers now need computational approaches to better understand lipid network perturbations in different diseases. Using a mouse model of type 2 diabetes with microvascular complications, we examined lipid levels in plasma and in renal, neural, and retinal tissues to identify shared and distinct lipid abnormalities...
December 13, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/29237478/am404-paracetamol-metabolite-prevents-prostaglandin-synthesis-in-activated-microglia-by-inhibiting-cox-activity
#3
Soraya Wilke Saliba, Ariel R Marcotegui, Ellen Fortwängler, Johannes Ditrich, Juan Carlos Perazzo, Eduardo Muñoz, Antônio Carlos Pinheiro de Oliveira, Bernd L Fiebich
BACKGROUND: N-arachidonoylphenolamine (AM404), a paracetamol metabolite, is a potent agonist of the transient receptor potential vanilloid type 1 (TRPV1) and low-affinity ligand of the cannabinoid receptor type 1 (CB1). There is evidence that AM404 exerts its pharmacological effects in immune cells. However, the effect of AM404 on the production of inflammatory mediators of the arachidonic acid pathway in activated microglia is still not fully elucidated. METHOD: In the present study, we investigated the effects of AM404 on the eicosanoid production induced by lipopolysaccharide (LPS) in organotypic hippocampal slices culture (OHSC) and primary microglia cultures using Western blot, immunohistochemistry, and ELISA...
December 13, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29237346/arachidonic-acid-reverses-xanthohumol-induced-insufficiency-in-a-human-first-trimester-extravillous-trophoblast-cell-line-htr-8-svneo-cells
#4
Ana Correia-Branco, Elisa Keating, Fátima Martel
We previously described a negative effect of xanthohumol (XN) upon placentation-related processes. We aimed to better characterize this effect by investigating the effect of XN upon the uptake of arachidonic acid (ARA), a crucial nutrient during pregnancy, by the HTR-8/SVneo human first-trimester extravillous trophoblast cell line and its relationship with the negative effect of XN upon placentation-related processes. Uptake of 14C-ARA (100 nM) was time dependent and inhibited by short-term (26 minutes) or long-term (24 hours) exposure to XN...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/29233001/arachidonic-acid-attenuates-brain-damage-in-a-rat-model-of-ischemia-reperfusion-by-inhibiting-inflammatory-response-and-oxidative-stress
#5
Y Qu, H-L Zhang, X-P Zhang, H-L Jiang
The aim of the present study was to study the effects of arachidonic acid (ARA) in a rat brain ischemia/reperfusion model induced by middle cerebral artery occlusion (MCAO). A total of 50 rats were randomly divided into five groups: control group, MCAO group, MCAO + ARA 0.3 g/kg group, MCAO + ARA 1 g/kg group, and MCAO + ARA 3 g/kg group. The MCAO + ARA groups received ARA by intraperitoneal injection daily for 14 consecutive days, while the rats in the control and MCAO groups were given equivalent volume of saline...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29232926/differential-effects-of-seh-inhibitors-on-the-proliferation-and-migration-of-vascular-smooth-muscle-cells
#6
Hyo Seon Kim, Sang Kyum Kim, Keon Wook Kang
Epoxyeicosatrienoic acid (EET) is a cardioprotective metabolite of arachidonic acid. It is known that soluble epoxide hydrolase (sEH) is involved in the metabolic degradation of EET. The abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) play important roles in the pathogenesis of atherosclerosis and restenosis. Thus, the present study investigated the effects of the sEH inhibitor 12-(((tricyclo(3.3.1.13,7)dec-1-ylamino)carbonyl)amino)-dodecanoic acid (AUDA) on platelet-derived growth factor (PDGF)-induced proliferation and migration in rat VSMCs...
December 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29232862/effect-of-oxylipins-terpenoid-precursors-and-wounding-on-soft-corals-secondary-metabolism-as-analyzed-via-uplc-ms-and-chemometrics
#7
Mohamed A Farag, Hildegard Westphal, Tarek F Eissa, Ludger A Wessjohann, Achim Meyer
The effect of three oxylipin analogues, a terpenoid intermediate and wounding on the secondary metabolism of the soft corals Sarcophyton glaucum and Lobophyton pauciflorum was assessed. Examined oxylipins included prostaglandin (PG-E1), methyl jasmonate (MeJA), and arachidonic acid (AA) in addition to the diterpene precursor geranylgeranylpyrophosphate (GGP). Post-elicitation, metabolites were extracted from coral heads and analyzed via UPLC-MS followed by multivariate data analyses. Both supervised and unsupervised data analyses were used for sample classification...
December 10, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29231216/aronia-citrus-juice-polyphenol-rich-juice-intake-and-elite-triathlon-training-a-lipidomic-approach-using-representative-oxylipins-in-urine
#8
Libia Alejandra García-Flores, Sonia Medina, Cristina Gómez, Craig E Wheelock, Roberto Cejuela, José Miguel Martínez-Sanz, Camille Oger, Jean-Marie Galano, Thierry Durand, Álvaro Hernández-Sáez, Federico Ferreres, Ángel Gil-Izquierdo
In the present study, we examined whether particular urinary oxylipins (isoprostanes (IsoPs), leukotrienes (LTs), prostaglandins (PGs), and thromboxanes (TXs)) in 16 elite triathletes could alter during 145 days of training. Within this time span, 45 days were dedicated to examining the effects of the intake of a beverage rich in polyphenols (one serving: 200 mL per day) supplemented in their diet. The beverage was a mixture of citrus juice (95%) and Aronia melanocarpa juice (5%) (ACJ). Fifty-two oxylipins were analyzed in the urine...
December 12, 2017: Food & Function
https://www.readbyqxmd.com/read/29229739/complete-assessment-of-whole-body-n-3-and-n-6-pufa-synthesis-secretion-kinetics-and-dha-turnover-in-a-rodent-model
#9
Adam H Metherel, R J Scott Lacombe, Rapha Eumll Chouinard-Watkins, Kathryn E Hopperton, Richard P Bazinet
Previous assessments of the PUFA biosynthesis pathway have focused on DHA and arachidonic acid synthesis. Here, we determined whole-body synthesis-secretion kinetics for all downstream products of PUFA metabolism, including direct measurements of DHA and n-6 docosapentaenoic acid (DPAn-6, 22:5n-6) turnover, and compared n-6 and n-3 homologue kinetics. We infused labeled α-linolenic acid (ALA, 18:3n-3), linoleic acid (LNA, 18:2n-6), DHA and DPAn-6 as 2H5-ALA, 13C18-LNA, 13C22-DHA or 13C22-DPAn-6. Eight 11-week-old Long Evans rats fed a 10% fat diet were infused with the labeled PUFAs over 3 h, and plasma enrichment of labeled products was measured every 30 min...
December 11, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/29228980/lipoxin-a4-reverses-mesenchymal-phenotypes-to-attenuate-invasion-and-metastasis-via-the-inhibition-of-autocrine-tgf-%C3%AE-1-signaling-in-pancreatic-cancer
#10
Liang Zong, Ke Chen, Zhengdong Jiang, Xin Chen, Liankang Sun, Jiguang Ma, Cancan Zhou, Qinhong Xu, Wanxing Duan, Liang Han, Jianjun Lei, Xuqi Li, Qingyong Ma, Zheng Wang
BACKGROUND: Pancreatic cancer is a lethal disease in part because of its potential for aggressive invasion and metastasis. Lipoxin A4 (LXA4) is one of the metabolites that is derived from arachidonic acid and that is catalyzed by 15-lipoxygenase (15-LOX), and it has recently been reported to exhibit anti-cancer effects. However, the role of LXA4 in pancreatic cancer remains to be elucidated. METHODS: Pancreatic cell lines were treated with vehicle or LXA4, and the invasive capacity was then assessed by Transwell assays...
December 11, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29228599/chicken-bile-powder-protects-against-%C3%AE-naphthylisothiocyanate-induced-cholestatic-liver-injury-in-mice
#11
Yi-Fei Li, Jia-Sheng Wu, Yuan-Yuan Li, Yan Dai, Min Zheng, Jia-Kai Zeng, Guo-Feng Wang, Tian-Ming Wang, Wen-Kai Li, Xue-Yan Zhang, Ming Gu, Cheng Huang, Li Yang, Zheng-Tao Wang, Yue-Ming Ma
This study explored the effects of chicken bile powder (CBP), a 2000-year-old Chinese medicine, on α-naphthyl isothiocyanate (ANIT)-induced intrahepatic cholestasis in mice. CBP treatment for 14 days significantly ameliorated ANIT-induced changes in serum alanine aminotransferase, aspartate aminotransferase, bile acids, bilirubin, γ-glutamyl transpeptidase, alkaline phosphatase, and liver tissue morphology. Serum metabolomics showed changes in 24 metabolites in ANIT-exposed mice; 16 of these metabolites were reversed by CBP treatment via two main pathways (bile acid biosynthesis and arachidonic acid metabolism)...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29227475/an-alox12-12-hete-gpr31-signaling-axis-is-a-key-mediator-of-hepatic-ischemia-reperfusion-injury
#12
Xiao-Jing Zhang, Xu Cheng, Zhen-Zhen Yan, Jing Fang, Xiaozhan Wang, Weijun Wang, Zhen-Yu Liu, Li-Jun Shen, Peng Zhang, Pi-Xiao Wang, Rufang Liao, Yan-Xiao Ji, Jun-Yong Wang, Song Tian, Xue-Yong Zhu, Yan Zhang, Rui-Feng Tian, Lin Wang, Xin-Liang Ma, Zan Huang, Zhi-Gang She, Hongliang Li
Hepatic ischemia-reperfusion (IR) injury is a common clinical issue lacking effective therapy and validated pharmacological targets. Here, using integrative 'omics' analysis, we identified an arachidonate 12-lipoxygenase (ALOX12)-12-hydroxyeicosatetraenoic acid (12-HETE)-G-protein-coupled receptor 31 (GPR31) signaling axis as a key determinant of the hepatic IR process. We found that ALOX12 was markedly upregulated in hepatocytes during ischemia to promote 12-HETE accumulation and that 12-HETE then directly binds to GPR31, triggering an inflammatory response that exacerbates liver damage...
December 11, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29227173/changes-in-platelet-function-with-inflammation-in-patients-undergoing-vascular-surgery
#13
Bartosz Olechowski, Vikram Khanna, Mark Mariathas, Alexander Ashby, Richard T Dalton, Ian Nordon, Nicola Englyst, Scott Harris, Zoe Nicholas, Kala Thayalasamy, Michael Mahmoudi, Nick Curzen
The role of platelets in ischaemic events is well established. Aspirin represents the default antiplatelet and blocks the metabolism of arachidonic acid (AA) at the cyclo-oxygenase enzyme (COX). AA is commonly used as a test of response to aspirin, but recent data raise uncertainty about the validity of this approach. Specifically, in some patients AA-induced clotting is not suppressed, but the level of COX-dependent AA metabolite, thromboxane B2 (TXB2) is negligible. Furthermore, AA-induced whole blood clotting varies dynamically in individuals, who are aspirin responsive according to TXB2 levels...
December 11, 2017: Platelets
https://www.readbyqxmd.com/read/29224225/down-regulation-of-15-pgdh-by-interleukin-1-beta-from-activated-macrophages-leads-to-poor-prognosis-in-pancreatic-cancer
#14
Kota Arima, Yoshihiro Komohara, Luke Bu, Masayo Tsukamoto, Rumi Itoyama, Keisuke Miyake, Tomoyuki Uchihara, Yoko Ogata, Shigeki Nakagawa, Hirohisa Okabe, Katsunori Imai, Daisuke Hashimoto, Akira Chikamoto, Yo-Ichi Yamashita, Hideo Baba, Takatsugu Ishimoto
Chronic inflammation has a crucial role in cancer development and the progression of various tumors, including pancreatic ductal adenocarcinoma (PDAC). The arachidonate cascade is a major inflammatory pathway that produces several metabolites, such as prostaglandin E2 (PGE2 ). The enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) degrades prostaglandin and is frequently decreased in several types of cancer; however, the molecular mechanisms of 15-PGDH suppression are unclear. The current study was conducted to elucidate the molecular mechanisms and clinical significance of 15-PGDH suppression in PDAC...
December 10, 2017: Cancer Science
https://www.readbyqxmd.com/read/29223463/terfenadine-metabolism-of-human-cytochrome-p450-2j2-containing-genetic-variations-g312r-p351l-and-p115l
#15
Dabin Jeong, Hyoung-Goo Park, Young-Ran Lim, Yejin Lee, Vitchan Kim, Myung-A Cho, Donghak Kim
The human cytochrome P450 2J2 is involved in several metabolic reactions, including the oxidation of important therapeutics and epoxidation of endogenous arachidonic acid. At least ten genetic variations of P450 2J2 have been identified, but their effects on enzymatic activity have not been clearly characterized. Here, we evaluated the functional effects of three genetic variations of P450 2J2 (G312R, P351L, and P115L). Recombinant enzymes of wild-type and three variant P450 2J2 were heterologously expressed in Escherichia coli and purified...
November 11, 2017: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29221817/polyunsaturated-fatty-acids-in-plasma-at-8%C3%A2-years-and-subsequent-allergic-disease
#16
Jessica Magnusson, Sandra Ekström, Inger Kull, Niclas Håkansson, Sara Nilsson, Magnus Wickman, Erik Melén, Ulf Risérus, Anna Bergström
BACKGROUND: Polyunsaturated fatty acids (PUFAs) are hypothesized to modulate the risk of allergic disease. However, evidence from previous studies is inconclusive, and limited longitudinal data exist using circulating biomarkers of PUFA intake and metabolism. OBJECTIVE: We aimed to investigate associations between n-3 and n-6 PUFAs at age 8 years and asthma, rhinitis, and aeroallergen sensitization at age 16 years. METHODS: Proportions of n-3 PUFAs (very long-chain n-3 [VLC n-3; sum of eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid] and α-linolenic acid) and n-6 PUFAs (linoleic acid and arachidonic acid [AA]) in blood samples at age 8 years were measured for 940 children from the prospective Swedish birth cohort BAMSE (Children, Allergy, Milieu, Stockholm, Epidemiology)...
November 29, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29221177/untargeted-serum-metabonomics-study-of-psoriasis-vulgaris-based-on-ultra-performance-liquid-chromatography-coupled-to-mass-spectrometry
#17
Li Li, Lu Chuan-Jian, Han Ling, Deng Jing-Wen, He Ze-Hui, Yan Yu-Hong, Zhang Zhong-Zhao
Psoriasis is a common, chronic, systemic inflammatory skin disease, the etiology and pathogenesis is unclear. An untargeted high-throughput metabonomics method based on liquid chromatography coupled to mass spectrometry was applied to study the serum metabolic changes in psoriasis vulgaris patients, and to discover serum potential biomarkers for identification, diagnosis and exploring pathogenesis of psoriasis. The serum metabolic profiles from 150 subjects (75 psoriasis patients and 75 healthy controls) were acquired, the raw spectrometric data were processed by multivariate statistical analysis, and 44 potential biomarkers were screened out and identified...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29217656/anti-inflammatory-effects-of-omega-3-fatty-acids-in-the-brain-physiological-mechanisms-and-relevance-to-pharmacology
#18
REVIEW
Sophie Layé, Agnès Nadjar, Corinne Joffre, Richard P Bazinet
Classically, polyunsaturated fatty acids (PUFA) were largely thought to be relatively inert structural components of brain, largely important for the formation of cellular membranes. Over the past 10 years, a host of bioactive lipid mediators that are enzymatically derived from arachidonic acid, the main n-6 PUFA, and docosahexaenoic acid, the main n-3 PUFA in the brain, known to regulate peripheral immune function, have been detected in the brain and shown to regulate microglia activation. Recent advances have focused on how PUFA regulate the molecular signaling of microglia, especially in the context of neuroinflammation and behavior...
January 2018: Pharmacological Reviews
https://www.readbyqxmd.com/read/29211867/effects-of-corn-dried-distillers-grains-with-solubles-on-performance-egg-quality-yolk-fatty-acid-composition-and-oxidative-status-in-laying-ducks
#19
D Ruan, A M Fouad, Q L Fan, W Chen, W G Xia, S Wang, Y Y Cui, Y Wang, L Yang, C T Zheng
The study investigated the effects of increasing content of corn distillers' dried grains with solubles (DDGS) in the diets of laying ducks on oxidative status, laying performance, egg quality, and egg yolk fatty acid composition. Longyan females (1080) with similar BW at 17 wk of age were randomly assigned to 6 treatment groups, each consisting of 6 replicates of 30 birds. The basal diet (I) was a typical corn-soybean ration while the experimental diets (II to VI) substituted corn DDGS for soybean meal and wheat bran and a small reduction of corn...
November 29, 2017: Poultry Science
https://www.readbyqxmd.com/read/29211789/glycerol-3-phosphate-acyltransferase-2-expression-modulates-cell-roughness-and-membrane-permeability-an-atomic-force-microscopy-study
#20
Elizabeth R Cattaneo, Eduardo D Prieto, Maria B Garcia-Fabiani, Mauro A Montanaro, Herve Guillou, Maria R Gonzalez-Baro
In mammalian cells, de novo glycerolipid synthesis begins with the acylation of glycerol-3-phosphate, catalyzed by glycerol-3-phosphate acyltransferases (GPAT). GPAT2 is a mitochondrial isoform primarily expressed in testis under physiological conditions, and overexpressed in several types of cancers and cancer-derived human cell lines where its expression contributes to the tumor phenotype. Using gene silencing and atomic force microscopy, we studied the correlation between GPAT2 expression and cell surface topography, roughness and membrane permeability in MDA-MB-231 cells...
2017: PloS One
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