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

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 nucleotide‐binding and oligomerization domain‐like receptor (NLR...

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Published inDrug development research Vol. 82; no. 6; pp. 815 - 825
Main Authors Cagli, Ali, Senol, Sefika Pinar, Temiz‐Resitoglu, Meryem, Guden, Demet Sinem, Sari, Ayse Nihal, Sahan‐Firat, Seyhan, Tunctan, Bahar
Format Journal Article
LanguageEnglish
Published Hoboken, USA John Wiley & Sons, Inc 01.09.2021
Wiley Subscription Services, Inc
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Summary: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 nucleotide‐binding 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, apoptosis‐associated 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 (gp91phox and p47phox) 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 pro‐inflammatory 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.
Bibliography:Funding information
Mersin Üniversitesi, Grant/Award Number: 2018‐3‐TP2‐3082
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ISSN:0272-4391
1098-2299
DOI:10.1002/ddr.21786