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. Issue 6 (8th February 2021)

• Record Type: Journal Article
• Authors: Cagli, Ali; Senol, Sefika Pinar; Temiz‐Resitoglu, Meryem; Guden, Demet Sinem; Sari, Ayse Nihal; Sahan‐Firat, Seyhan; Tunctan, Bahar
• Is Part Of: Drug development research. Volume 82:Issue 6(2021)
• Page Start: 815
• Page End: 825
• Publication Date: 2021-02-08
• Subjects: caspase‐11 inflammasome -- inflammatory hyperalgesia -- NLRC4/ASC/pro‐caspase‐1 inflammasome -- NOS -- NOX -- soluble epoxide hydrolase; Drug development -- Periodicals; Drugs -- Research -- Periodicals; 615.19
• DOI: 10.1002/ddr.21786
• Languages: English
• ISSNs: 0272-4391

Abstract

Abstract: 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 (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 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.