Heng Fan1, Yu Zhao2, Jian-Hua Zhu1. 1. Department of Intensive Care Unit, Ningbo First Hospital, Ningbo, China. 2. Department of Nephrology, Ningbo Urology and Nephrology Hospital, Ningbo, China.
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.
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.