Protective effect of hydroxysafflor yellow A against acute kidney injury via the TLR4/NF-κB signaling pathway

Abstract

This study aimed to evaluate the protective effect of hydroxysafflor yellow A (HSYA) on ischemia/reperfusion (I/R)-induced acute kidney injury via the TLR4/NF-κB pathway, both in vitro and in vivo. Rats were subjected to removal of the right kidney and I/R injury to the left kidney. Rats subjected to renal I/R injury were treated with HSYA at 0.5 h prior to I/R injury. Renal function, histopathological analysis, and cells apoptosis were measured in vivo. In vitro, proximal renal tubular cells (HK-2) were subjected to hypoxia/reoxygenation (H/R). Apoptotic cell death and inflammatory cytokines, Toll-like receptor 4 (TLR4), and nuclear factor (NF)-κB expression were determined. Treatment of I/R rats with HSYA markedly reduced the levels of serum creatinine and blood urea nitrogen, attenuated renal cell apoptosis, alleviated changes in renal tissue morphology, and reduced IL-1β, TNF-α, and caspase-3 release. In vitro, HSYA effectively decreased NF-κB p65 and inflammatory cytokines, such as IL-1β, TNF-α, and IL-6. Thus, HSYA can protect renal function from I/R injury by ameliorating acute kidney injury and partly by promoting tubular cell survival via the TLR4/NF-κB pathway. These results suggest that HSYA can be used to prevent I/R-induced acute kidney injury.