Eicosanoids derived from cytochrome P450 pathway of arachidonic acid and inflammatory shock

Tunçtan, Bahar; Şenol, Şefika Pınar; Temiz-Resitoglu, Meryem; Guden, Demet Sinem; Şahan-Fırat, Seyhan; Falck, John R.; Malik, Kafait U.

doi:10.1016/j.prostaglandins.2019.106377

Cited by 17 publications

(21 citation statements)

References 176 publications

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“…AA is released from cell membrane phospholipids primarily by phospholipase A 2 (PLA 2 ) and, in turn, metabolized through three different pathways involving cyclooxygenase (COX), cytochrome P450 (CYP) enzymes (ω-hydroxylases and epoxygenases), or lipoxygenase (LOX) ( Figure 2 ) [ 37 , 38 ]. Various substances such as acetylcholine and shear stress can activate PLA 2 and trigger the downstream mechanism in vascular endothelial cells (ECs).…”

Section: Pathways Involved In Arachidonic Acid Metabolismmentioning

confidence: 99%

Effects of Arachidonic Acid Metabolites on Cardiovascular Health and Disease

Zhou¹,

Khan

Xiao

et al. 2021

IJMS

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Arachidonic acid (AA) is an essential fatty acid that is released by phospholipids in cell membranes and metabolized by cyclooxygenase (COX), cytochrome P450 (CYP) enzymes, and lipid oxygenase (LOX) pathways to regulate complex cardiovascular function under physiological and pathological conditions. Various AA metabolites include prostaglandins, prostacyclin, thromboxanes, hydroxyeicosatetraenoic acids, leukotrienes, lipoxins, and epoxyeicosatrienoic acids. The AA metabolites play important and differential roles in the modulation of vascular tone, and cardiovascular complications including atherosclerosis, hypertension, and myocardial infarction upon actions to different receptors and vascular beds. This article reviews the roles of AA metabolism in cardiovascular health and disease as well as their potential therapeutic implication.

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Section: Pathways Involved In Arachidonic Acid Metabolismmentioning

confidence: 99%

Effects of Arachidonic Acid Metabolites on Cardiovascular Health and Disease

Zhou¹,

Khan

Xiao

et al. 2021

IJMS

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“…It has also been reported that, when injected to rats systemically, lower doses of LPS induce hyperalgesia, whereas higher doses cause analgesia (Romanovsky et al, 1996). The pathogenesis of inflammatory pain appears to be as a result of circulating bacterial cell wall components (e.g., endotoxin) in addition to host immune and inflammatory responses like arachidonic acid-derived eicosanoids and reactive nitrogen or oxygen species (RNS/ROS) due to mainly cyclooxygenases (COXs), cytochrome P450s (CYPs), nitric oxide (NO), synthases (NOSs), and nicotinamide adenine dinucleotide phosphate oxidase (NOX) in addition to pro-inflammatory cytokines (such as tumor necrosis factor [TNF]-α, interleukin [IL]-1β, IL-6), and caspases (Petho & Reeh, 2012;Tunctan et al, 2019;Zouikr & Karshikoff, 2017).…”

Section: Introductionmentioning

confidence: 99%

Soluble epoxide hydrolase inhibitor trifluoromethoxyphenyl‐3‐(1‐propionylpiperidin‐4‐yl)urea prevents hyperalgesia through regulating NLRC4 inflammasome‐related pro‐inflammatory and anti‐inflammatory signaling pathways in the lipopolysaccharide‐induced pain mouse model

Cagli

Şenol

Temiz-Resitoglu

et al. 2021

Drug Development Research

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Epoxyeicosatrienoic acids (EETs) have anti-inflammatory effects and soluble epoxide hydrolase (sEH) inhibition might be a useful therapeutic approach to manage inflammatory disorders. The purpose of the study was to investigate whether nucleotidebinding and oligomerization domain-like receptor (NLR) C4 inflammasome-related pro-inflammatory and anti-inflammatory signaling pathways in the central nervous system (CNS) participates in the effect of trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea (TPPU), a potent sEH inhibitor, to prevent hyperalgesia in the LPS-induced pain mouse model. The latency of pain within 30 s was measured by the hot plate test in male mice injected with saline, lipopolysaccharide (LPS) (10 mg/kg), and/or TPPU (0.3, 0.5, or 1 mg/kg) after 6 h. Hyperalgesia induced by LPS was associated with decreased 14,15-dihydroxyeicosatrienoic acid and interleukin (IL)-1β levels and enhanced expression of NLRC4, apoptosisassociated speck-like protein containing a caspase activation and recruitment domain (ASC), caspase-1 p20, IL-1β, and caspase-11 p20 in the brains and spinal cords of the animals. Besides the increased expression of nicotinamide adenine dinucleotide phosphate oxidase (NOX) subunits (gp91 phox and p47 phox ) and nitrotyrosine, a decrease in NLRC3, inducible nitric oxide synthase (iNOS), and neuronal NOS (nNOS) expression was also observed in the tissues of LPS-treated mice. TPPU at 0.5 mg/kg dose prevented the changes induced by LPS. Likely, decreased activity of proinflammatory NLRC4/ASC/pro-caspase-1 and caspase-11 inflammasomes and NOX in addition to enhanced levels of anti-inflammatory EETs and expression of NLRC3, iNOS, and nNOS in the CNS of mice participates in the protective effect of TPPU against LPS-induced hyperalgesia.

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“…Hyperglycemia is potentially detrimental in critically ill humans [109], and numerous studies have investigated the use of insulin to control sepsis-associated hyperglycemia in humans [110]. The decreased abundance of arachidonic acid in nonsurvivors is also noteworthy, because this lipid mediator is the parent molecule from which numerous eicosanoid inflammatory mediators are derived [111]. Alterations in the concentrations of the bioactive mediators derived from arachidonic acid have been associated with outcome in sepsis in humans [112].…”

Section: Plos Onementioning

confidence: 99%

Identifying potential biomarkers and therapeutic targets for dogs with sepsis using metabolomics and lipidomics analyses

et al. 2022

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Sepsis is a diagnostic and therapeutic challenge and is associated with morbidity and a high risk of death. Metabolomic and lipidomic profiling in sepsis can identify alterations in metabolism and might provide useful insights into the dysregulated host response to infection, but investigations in dogs are limited. We aimed to use untargeted metabolomics and lipidomics to characterize metabolic pathways in dogs with sepsis to identify therapeutic targets and potential diagnostic and prognostic biomarkers. In this prospective observational cohort study, we examined the plasma metabolomes and lipidomes of 20 healthy control dogs and compared them with those of 21 client-owned dogs with sepsis. Patient data including signalment, physical exam findings, clinicopathologic data and clinical outcome were recorded. Metabolites were identified using an untargeted mass spectrometry approach and pathway analysis identified multiple enriched metabolic pathways including pyruvaldehyde degradation; ketone body metabolism; the glucose-alanine cycle; vitamin-K metabolism; arginine and betaine metabolism; the biosynthesis of various amino acid classes including the aromatic amino acids; branched chain amino acids; and metabolism of glutamine/glutamate and the glycerophospholipid phosphatidylethanolamine. Metabolites were identified with high discriminant abilities between groups which could serve as potential biomarkers of sepsis including 13,14-Dihydro-15-keto Prostaglandin A2; 12(13)-DiHOME (12,13-dihydroxy-9Z-octadecenoic acid); and 9-HpODE (9-Hydroxyoctadecadienoic acid). Metabolites with higher abundance in samples from nonsurvivors than survivors included 3-(2-hydroxyethyl) indole, indoxyl sulfate and xanthurenic acid. Untargeted lipidomic profiling revealed multiple sphingomyelin species (SM(d34:0)+H; SM(d36:0)+H; SM(d34:0)+HCOO; and SM(d34:1D3)+HCOO); lysophosphatidylcholine molecules (LPC(18:2)+H) and lipophosphoserine molecules (LPS(20:4)+H) that were discriminating for dogs with sepsis. These biomarkers could aid in the diagnosis of dogs with sepsis, provide prognostic information, or act as potential therapeutic targets.

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Eicosanoids derived from cytochrome P450 pathway of arachidonic acid and inflammatory shock

Cited by 17 publications

References 176 publications

Effects of Arachidonic Acid Metabolites on Cardiovascular Health and Disease

Effects of Arachidonic Acid Metabolites on Cardiovascular Health and Disease

Soluble epoxide hydrolase inhibitor trifluoromethoxyphenyl‐3‐(1‐propionylpiperidin‐4‐yl)urea prevents hyperalgesia through regulating NLRC4 inflammasome‐related pro‐inflammatory and anti‐inflammatory signaling pathways in the lipopolysaccharide‐induced pain mouse model

Identifying potential biomarkers and therapeutic targets for dogs with sepsis using metabolomics and lipidomics analyses

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