Effect of TRPA1 agonist ASP7663 and antagonist HC-030031 on Kidney Damage in model of cecal ligation and puncture-induced sepsis in rats

Transient receptor potential ankyrin 1 (TRPA1) channels have been shown to be associated with kidney injury and have immunomodulatory effects. In this study, we investigated the effect of TRPA1 agonist ASP7663 and antagonist HC-030031 on kidney injury in an experimental sepsis model induced by cecal ligation and puncture (CLP) in rats. Rats were divided into 4 groups as Control, CLP, CLP+3 mg/kg ASP7663, CLP+30 mg/kg HC030031. After CLP, 3 mg/kg ASP7663 was administered to one of the treatment groups and 30 mg/kg HC-030031 was administered to the other. In this study, serum blood urea nitrogen (BUN), creatinine (Cre), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), interleukin 18 (IL-18), neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) levels, which were increased due to CLP, were significantly decreased by HC-030031 administration (P<0.05). Similarly, increased Tolllike receptor 4 (TLR4), phosphorylated NF-κB, phosphorylated IκB-α, TNF-α, IL-1β, interleukin 6 (IL-6), caspase-3 and caspase-8 immunoreactivity levels and histopathological damage in kidney tissue due to CLP were decreased by HC-030031 treatment (P<0.05). The TRPA1 antagonist HC-030031 attenuated renal injury through its anti-inflammatory and antiapoptotic effects in an experimental sepsis model. 2025, xviii + 124 Pages Keywords: Kidney, Sepsis, TRPA1 Channels, ASP7663, HC-030031