The ameliorative effect of inhibiting transient receptor potential ankyrin 1 on sepsis-induced kidney injury via the toll-like receptor 4/nuclear factor-kappa B pathway

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dc.contributor.authorFirat, Semanur
dc.contributor.authorCakir, Murat
dc.contributor.authorAydin, Ali
dc.contributor.authorBircan, Burak
dc.contributor.authorSekerci, Guldeniz
dc.contributor.authorTekin, Suat
dc.date.accessioned2026-04-04T13:35:09Z
dc.date.available2026-04-04T13:35:09Z
dc.date.issued2025
dc.departmentİnönü Üniversitesi
dc.description.abstractBackground Kidneys are among the organs most affected by sepsis caused by the host's uncontrolled immune response to infection. Transient receptor potential ankyrin 1 (TRPA1) channels have been shown to be associated with renal damage. TRPA1 channels also have a role in regulating intracellular Ca2+ levels, cytokine production, and immune response control. In this study, the effects of TRPA1 agonist ASP7663 and antagonist HC-030031 on renal injury in an experimental sepsis model were examined. Materials and methods Rats underwent cecal ligation and perforation (CLP) to serve as an experimental sepsis model. One of the two treatment groups received a TRPA1 agonist ASP7663, while the other received a TRPA1 antagonist HC030031. Serum levels of BUN, creatinine (Cre), TNF-alpha, IL-1 beta, IL-18, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) were measured. Histopathological examination of kidney tissue was performed. Immunohistochemical analysis of Toll-like receptor 4 (TLR4), NF-kappa B, phosphorylated NF-kappa B, I kappa B-alpha, phosphorylated I kappa B-alpha, TNF-alpha, IL-1 beta, IL-6, caspase-3, and caspase-8 levels was conducted in kidney tissue. Results CLP administration raised serum levels of BUN, Cre, TNF-alpha, IL-1 beta, IL-18, NGAL, and KIM-1 (P < 0.05). It also caused histopathological damage to kidney tissue. Additionally, CLP increased levels of TLR4, phosphorylated NF-kappa B, phosphorylated I kappa B-alpha, TNF-alpha, IL-1 beta, IL-6, caspase-3, and caspase-8 in kidney tissue (P < 0.05). The TRPA1 antagonist HC-030031 reversed all pathological changes in serum and kidney tissue caused by CLP. Conclusion TRPA1 antagonist HC-030031 showed a protective effect in an experimental sepsis model by reducing kidney damage through its anti-inflammatory and anti-apoptotic effects.
dc.description.sponsorshipYozgat Bozok University Scientific Research Projects Unit [TYL-2023-1292]
dc.description.sponsorshipThis study was funded by Yozgat Bozok University Scientific Research Projects Unit. (Project no: TYL-2023-1292) .
dc.identifier.doi10.1016/j.ejphar.2025.178285
dc.identifier.issn0014-2999
dc.identifier.issn1879-0712
dc.identifier.orcid0009-0008-8586-3433
dc.identifier.orcid0000-0002-2066-829X
dc.identifier.pmid41138837
dc.identifier.scopus2-s2.0-105020987563
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1016/j.ejphar.2025.178285
dc.identifier.urihttps://hdl.handle.net/11616/109647
dc.identifier.volume1007
dc.identifier.wosWOS:001607966400002
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherElsevier
dc.relation.ispartofEuropean Journal of Pharmacology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WOS_20250329
dc.subjectAcute kidney injury
dc.subjectCecal ligation and puncture
dc.subjectSepsis
dc.subjectTRPA1 channels
dc.titleThe ameliorative effect of inhibiting transient receptor potential ankyrin 1 on sepsis-induced kidney injury via the toll-like receptor 4/nuclear factor-kappa B pathway
dc.typeArticle

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