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.
Highlights
Acute kidney injury (AKI) is a clinical syndrome with very high mortality rates
Our results showed that hydroxysafflor yellow A (HSYA) prevented renal functional alterations induced by ischemia/ reperfusion (I/R) injury partly by inhibiting activation of the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB pathway
Rats pre-treated with HSYA (I/R + HSYA group) did not exhibit significant increases in blood urea nitrogen (BUN) (38.31 ± 2.78 mmol/L) and serum creatinine (SCr) (255.00 ± 18.76 μmol/L) levels
Summary
Acute kidney injury (AKI) is a clinical syndrome with very high mortality rates. AKI-associated costs account for 5% of hospital expenditures[1] and 1% of overall health expenditures[2] in developed countries. Toll-like receptor 4 (TLR4) is a key regulator of the pro-inflammatory transcription factor (NF-κB) and plays a dominant role in mediating sterile kidney damage following renal I/R injury[10]. NF-κB is a member of the family of pleiotropic transcription factors which play important roles in regulating the expression of genes involved in various cell processes, including inflammation[14,15]. TLR4 activation induces the expression of NF-κB-dependent proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β16. These cytokines induce tubular epithelial cell necrosis and renal tubular atrophy[17]. Our results showed that HSYA prevented renal functional alterations induced by I/R injury partly by inhibiting activation of the TLR4/NF-κB pathway
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