Lipids in Toxicology and Lung Disease DOI

Hannah B. Lovins,

Arjun Pitchai, Laura Leuenberger

et al.

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

Characterization of oxylipins in Antarctic krill oil (Euphausia superba) during storage based on RPLC–MS/MS analysis DOI
Nan Meng, Xincen Wang, Yu Song

et al.

Food Chemistry, Journal Year: 2024, Volume and Issue: 445, P. 138702 - 138702

Published: Feb. 10, 2024

Language: Английский

Citations

9
Inhibition of Soluble Epoxide Hydrolase Reduces Inflammation and Myocardial Injury in Arrhythmogenic Cardiomyopathy DOI Creative Commons

Dipak Panigrahy,

Abigail Kelly,

Katherine Quinlivan

et al.

JACC Basic to Translational Science, Journal Year: 2025, Volume and Issue: 10(3), P. 367 - 380

Published: Feb. 5, 2025

We analyzed the role of pro- and anti-inflammatory eicosanoids in pathogenesis arrhythmogenic cardiomyopathy (ACM). Lipidomics revealed reduced levels oxylipins plasma increased pro-inflammatory hearts Dsg2mut/mut mice, a preclinical model ACM. Disease features were reversed vitro rat ventricular myocytes expressing mutant JUP by epoxyeicosatrienoic acid 14-15-EET, whereas 14,15-EEZE, which antagonizes 14,15-EET receptor, intensified nuclear accumulation desmosomal protein plakoglobin. Inhibition soluble epoxide hydrolase (sEH), an enzyme that converts EETs into polar, less active diols, prevented progression myocardial injury mice promoted recovery contractile function. This was associated with expression genes involved innate immune signaling fewer injurious macrophages CCR2. These results suggest contribute to sEH may be effective, mechanism-based therapy for ACM patients.

Language: Английский

Citations

1
Multi-tissue profiling of oxylipins reveal a conserved up-regulation of epoxide:diol ratio that associates with white adipose tissue inflammation and liver steatosis in obesity DOI Creative Commons
Charlotte Hateley,

Antoni Olona,

Laura Halliday

et al.

EBioMedicine, Journal Year: 2024, Volume and Issue: 103, P. 105127 - 105127

Published: April 26, 2024

Background Obesity drives maladaptive changes in the white adipose tissue (WAT) which can progressively cause insulin resistance, type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated liver disease (MASLD).Obesity-mediated loss of WAT homeostasis trigger steatosis through dysregulated lipid pathways such as those related to polyunsaturated fatty acid (PUFA)-derived oxylipins.However, exact relationship between oxylipins syndrome remains elusive cross-tissue dynamics are ill-defined.Methods We quantified PUFA-related oxylipin species omental WAT, biopsies plasma 88 patients undergoing bariatric surgery (female N = 79) 9 4) upper gastrointestinal surgery, using UPLC-MS/MS.We integrated abundance with phenotypes (adipogenesis, adipocyte hypertrophy, macrophage infiltration, I VI collagen remodelling) severity MASLD (steatosis, inflammation, fibrosis) each biopsy.The integrative analysis was subjected (i) adjustment for known risk factors and, (ii) control potential drug-effects UPLC-MS/MS metformin-treated fat explants ex vivo.Findings reveal a generalized down-regulation cytochrome P450 (CYP)-derived diols during obesity conserved plasma.Notably, epoxide:diol ratio, indicative soluble epoxide hydrolyse (sEH) activity, increases inflammation/fibrosis, hepatic T2DM.Increased 12,13-EpOME:DiHOME is marker worsening obesity.Interpretation These findings suggest dampened sEH activity possible role major organs liver.They also have implications view clinical trials based on inhibition syndrome.

Language: Английский

Citations

6
Phenyl-benzyl-ureas with pyridazinone motif: Potent soluble epoxide hydrolase inhibitors with enhanced pharmacokinetics and efficacy in a paclitaxel-induced neuropathic pain model DOI
Deniz Lengerli,

Arooj Bakht,

Kübra Çalışkan

et al.

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 117510 - 117510

Published: March 1, 2025

Language: Английский

Citations

0
Microglial pro-inflammatory mechanisms induced by monomeric C-reactive protein are counteracted by soluble epoxide hydrolase inhibitors DOI Creative Commons
Clara Bartra, Kristijan Vuraić, Yi Yuan

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 155, P. 114644 - 114644

Published: April 10, 2025

Monomeric C-reactive protein (mCRP) is a pro-inflammatory molecule generated by the dissociation of native CRP. Clinical and experimental studies suggest that mCRP deposition in brain induces Alzheimer's disease (AD) pathology cognitive loss. Pathological neuroinflammation increasingly suggested as relevant AD. Innovative therapies against are desperately needed, inhibitors enzyme soluble epoxide hydrolase (sEH) promising new generation anti-inflammatory drugs. Mouse primary microglia BV2 cell line cultures were exposed to analyze its mechanisms. sEH inhibitors, both newly synthesized UB-SCG-55 UB-SCG-65, reference agent TPPU, tested for their action mCRP. Phenotypic changes analyzed through imaging techniques, well molecular analysis inflammatory mediators gene activation pathways. Results show triggers response three main pathways: iNOS, NLRP3, COX-2, followed increased cytokine generation. Polarization toward M1-like phenotype was confirmed morphological analysis. Also, can bind cross membrane, providing further insight into mechanisms action. effective induction reactive microglial phenotype. The first-line compound emerged most potent injury. Therefore, direct provides evidence role triggering exacerbating neurodegenerative diseases with neuroinflammatory component, such Furthermore, protection given confirms potential innovative drugs deleterious effects neuroinflammation.

Language: Английский

Citations

0
Role of the soluble epoxide hydrolase in keratinocyte proliferation and sensitivity of skin to inflammatory stimuli DOI Creative Commons

Zumer Naeem,

Sven Zukunft, Arnaud Huard

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 171, P. 116127 - 116127

Published: Jan. 9, 2024

The lipid content of skin plays a determinant role in its barrier function with particularly important attributed to linoleic acid and derivatives. Here we explored the consequences interfering soluble epoxide hydrolase (sEH) on homeostasis. sEH; which converts fatty epoxides generated by cytochrome P450 enzymes their corresponding diols, was largely restricted epidermis enriched sEH-generated diols. Global deletion sEH increased levels epoxides, including acid-derived epoxide; 12,13-epoxyoctadecenoic (12,13-EpOME), basal keratinocyte proliferation. (sEH-/- mice) resulted thicker differentiated spinous corneocyte layers compared wild-type mice, hyperkeratosis phenotype that reproduced mice treated inhibitor. made sensitive inflammation sEH-/- developed imiquimod-induced psoriasis plaques than control group were more prone triggered mechanical stress pronounced infiltration activation neutrophils as well vascular leak 12,13-EpOME leukotriene (LT) B4 levels. Topical treatment LTB4 antagonist after stripping successfully inhibited neutrophil both wild type skin. While 12,13-EpoME had no effect trans-endothelial migration neutrophils, like LTB4, it effectively induced adhesion activation. These observations indicate while accumulation sEH-deficient could be increase levels, contribute Our identify protective should taken into account when designing future clinical trials inhibitors.

Language: Английский

Citations

2
The Role of Arachidonic Acid Metabolizing Cytochromes P450 in the Control of Cardiovascular Functions DOI
M. L. Perepechaeva, A. Yu. Grishanova

Biochemistry (Moscow) Supplement Series B Biomedical Chemistry, Journal Year: 2024, Volume and Issue: 18(3), P. 192 - 213

Published: Sept. 1, 2024

Language: Английский

Citations

1
Salt-sensitive hypertension in GR mutant rats is associated with altered plasma polyunsaturated fatty acid levels and aortic vascular reactivity DOI Creative Commons
Sophia N. Verouti, Gilles Aeschlimann, Qing Wang

et al.

Pflügers Archiv - European Journal of Physiology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 10, 2024

Language: Английский

Citations

0
The Role of Hydroxyeicosatetraenoic Acids in the Regulation of Inflammation in Bronchial Asthma DOI

Oxana Kytikova,

I. S. Kovalenko, Т. П. Новгородцева

et al.

Doklady Biochemistry and Biophysics, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 16, 2024

Language: Английский

Citations

0
A regulatory loop involving the cytochrome P450-soluble epoxide hydrolase axis and TGF-β signaling DOI Creative Commons
Xiaoming Li,

Sebastian Kempf,

Fredy Delgado Lagos

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(10), P. 110938 - 110938

Published: Sept. 16, 2024

Language: Английский

Citations

0