S-nitrosoglutathione protects lipopolysaccharide-induced acute kidney injury by inhibiting toll-like receptor 4–nuclear factor-κB signal pathway

Abstract

Objectives To investigate the therapeutic effects and mechanisms of S‐nitrosoglutathione (SNG) on acute kidney injury (AKI) induced by lipopolysaccharide (LPS). Methods We established an AKI model by intraperitoneal administration of LPS in mice and LPS‐induced human kidney (HK‐2) cells in vitro. We obtained the kidney tissues from mice for histopathological examination, examined inflammatory cytokines by enzyme‐linked immunosorbent assay and measured the expression levels of toll‐like receptor 4–nuclear factor‐κB (TLR4–NF‐κB) signal pathway‐related proteins by Western blotting. Key findings Pretreatment of SNG effectively improved the kidney function, reduced the pathological damage score of kidney in mice and decreased the expression levels of IL‐1β, IL‐6 and TNF‐α in a dose‐dependent manner in vivo and in vitro. Furthermore, pretreatment of SNG also repressed TLR4, phosphorylated NF‐κB IκBα, IKKβ and p65 expression levels in HK‐2 cells induced by LPS. Conclusions S‐nitrosoglutathione attenuates the severity of LPS‐induced AKI by inhibiting the TLR4–NF‐κB signalling pathway and may act as a protective agent for septic AKI.