P450 Eicosanoids and Reactive Oxygen Species Interplay in Brain Injury and Neuroprotection

Liu, Xuehong; Davis, Catherine M.; Alkayed, Nabil J.

doi:10.1089/ars.2017.7056

Cited by 23 publications

(17 citation statements)

References 215 publications

(330 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The most discriminant oxylipin was 5,6-DHET which is one of the inactive metabolites of the epoxyeicosatrienoic acids (EETs) which are endogenous mediators that regulate cerebral blood flow and have protective effects against cerebral ischaemia 26 . Levels of EETs and their metabolites 27 , 28 have been found to be altered in patients who have suffered from stroke compared to healthy controls and species of EETs have been implicated in the pathogenesis of stroke, cerebral haemorrhage and traumatic brain injury 29 .…”

Section: Discussionmentioning

confidence: 99%

Profiling inflammatory markers in patients with pneumonia on intensive care

Antcliffe

Wolfer

O’Dea

et al. 2018

Sci Rep

View full text Add to dashboard Cite

Clinical investigations lack predictive value when diagnosing pneumonia, especially when patients are ventilated and develop ventilator associated pneumonia (VAP). New tools to aid diagnosis are important to improve outcomes. This pilot study examines the potential for a panel of inflammatory mediators to aid in the diagnosis. Forty-four ventilated patients, 17 with pneumonia and 27 with brain injuries, eight of whom developed VAP, were recruited. 51 inflammatory mediators, including cytokines and oxylipins, were measured in patients’ serum using flow cytometry and mass spectrometry. The mediators could separate patients admitted to ICU with pneumonia compared to brain injury with an area under the receiver operating characteristic curve (AUROC) 0.75 (0.61–0.90). Changes in inflammatory mediators were similar in both groups over the course of ICU stay with 5,6-dihydroxyeicosatrienoic and 8,9-dihydroxyeicosatrienoic acids increasing over time and interleukin-6 decreasing. However, brain injured patients who developed VAP maintained inflammatory profiles similar to those at admission. A multivariate model containing 5,6-dihydroxyeicosatrienoic acid, 8,9-dihydroxyeicosatrienoic acid, intercellular adhesion molecule-1, interleukin-6, and interleukin-8, could differentiate patients with VAP from brain injured patients without infection (AUROC 0.94 (0.80–1.00)). The use of a selected group of markers showed promise to aid the diagnosis of VAP especially when combined with clinical data.

show abstract

Section: Discussionmentioning

confidence: 99%

Profiling inflammatory markers in patients with pneumonia on intensive care

Antcliffe

Wolfer

O’Dea

et al. 2018

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Epoxyeicosatrienoic acids (EETs) mediate vasodilatation, reduce inflammation, attenuate OS and block the pathological endoplasmic reticulum (ER) stress response (10,11). The soluble epoxide hydrolase enzyme (sEH, EC 3.3.2.10, EPHX2), widely expressed in relatively high abundance in the murine and human brains (12,13), converts EETs and other epoxyfatty acids (EpFA) to their corresponding dihydroxyeicosatrienoic acids (DHETs), whereby diminishing, eliminating, or altering the beneficial effects of EETs (14) (Fig.…”

Section: Introductionmentioning

confidence: 99%

Pharmacological inhibition of soluble epoxide hydrolase as a new therapy for Alzheimer’s Disease

Griñán-Ferré

Codony

Pujol

et al. 2019

Preprint

View full text Add to dashboard Cite

The inhibition of the enzyme soluble epoxide hydrolase (sEH) has demonstrated clinical therapeutic effects in several peripheral inflammatory-related diseases, with two compounds that have entered clinical trials. However, the role of this enzyme in the neuroinflammation process has been largely neglected. Herein, we disclose the pharmacological validation of sEH as a novel target for the treatment of Alzheimer's Disease (AD). Of interest, we have found that sEH is upregulated in brains from AD patients. We have evaluated the cognitive impairment and the pathological hallmarks in two models of age-related cognitive decline and AD using three structurally different and potent sEH inhibitors as chemical probes. Our findings supported our expectations on the beneficial effects of central sEH inhibition, regarding of reducing cognitive impairment, tau hyperphosphorylation pathology and the number of amyloid plaques.Interestingly, our results suggest that reduction of inflammation in the brain is a relevant therapeutic strategy for all stages of AD.

show abstract

“…The Tx-prostanoid receptor (TP) may mediate the action of HETEs and EETs on ROS production. Activation of TP stimulates ROS production in many different cells and tissues, and HETEs may activate, but EETs inhibit TP activity to control ROS production (5).…”

Section: Ros As a Messenger For The Actions Of Lipid Mediatorsmentioning

confidence: 99%

“…In contrast, excessive ROS were also found to suppress PGE2 generation, reducing the protective effects of this PG in face of pathological challenges. In some disease states such as ischemia and inflammation, increased inflammatory cytokines and ROS may increase the activity of PLA2, resulting in enhanced release of AA from cell membranes and activating CYP450 metabolism of AA to produce HETEsinduced pathological changes (5).…”

Section: Lipid Mediators As a Target For The Actions Of Rosmentioning

confidence: 99%

Bioactive Lipids and Redox Signaling: Molecular Mechanism and Disease Pathogenesis

Gulbins

2018

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

The actions of bioactive lipids and reactive oxygen species (ROS) are usually coupled, and their interplay is a common and important mechanism mediating tissue injury, inflammation, and other pathologies. Understanding the interplay of ROS and lipid mediators will extend horizons for researchers to clarify the pathogenesis of different diseases and help identify therapeutic targets for treatment of these diseases. Some bioactive lipids are converted into oxidized lipids during cell or tissue oxidative stress such as isoprostanes and isoketals, which are even more bioactive than their precursors. Moreover, many enzymes that produce lipid mediators such as prostaglandin H synthases, lipoxygenases, and cytochrome P450 isoforms may catalyze the production of ROS. Bioactive lipids-lysophospholipids, sphingolipids, or deposited lipids in cells-are shown to stimulate redox enzymes to produce ROS. In addition, a lipid-channel-ROS axis in different organelles may be associated with the crosstalk of ROS and bioactive lipids. This Forum focuses on the crosstalk of ROS with sphingolipids, P450 eicosanoids, lysophospholipids, and deposited plasma lipids and related novel signaling pathway in their reciprocal actions, which is expected to provide novel insights into the pathogenesis of different diseases associated with the participation of these lipid mediators. It is imperative to further understand the molecular mechanism mediating the crosstalk of ROS with specific lipid mediators and to develop more effective therapeutic strategies to target the interplay of ROS and lipid mediators for treatment specific to different organ diseases. Antioxid. Redox Signal. 00, 000-000.

show abstract

P450 Eicosanoids and Reactive Oxygen Species Interplay in Brain Injury and Neuroprotection

Cited by 23 publications

References 215 publications

Profiling inflammatory markers in patients with pneumonia on intensive care

Profiling inflammatory markers in patients with pneumonia on intensive care

Pharmacological inhibition of soluble epoxide hydrolase as a new therapy for Alzheimer’s Disease

Bioactive Lipids and Redox Signaling: Molecular Mechanism and Disease Pathogenesis

Contact Info

Product

Resources

About