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
Küçük Resim Yok
Tarih
2025
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Elsevier
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Background 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.
Açıklama
Anahtar Kelimeler
Acute kidney injury, Cecal ligation and puncture, Sepsis, TRPA1 channels
Kaynak
European Journal of Pharmacology
WoS Q Değeri
Q1
Scopus Q Değeri
Q1
Cilt
1007
