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.

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-α, IL-1β, 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-κB, phosphorylated NF-κB, IκB-α, phosphorylated IκB-α, TNF-α, IL-1β, IL-6, caspase-3, and caspase-8 levels was conducted in kidney tissue.

RESULTS

CLP administration raised serum levels of BUN, Cre, TNF-α, IL-1β, 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-κB, phosphorylated IκB-α, TNF-α, IL-1β, 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.