Rhein prevents endotoxin-induced acute kidney injury by inhibiting NF-κB activities

This study aimed to explore the effect and mechanisms of rhein on sepsis-induced acute kidney injury by injecting lipopolysaccharide (LPS) and cecal ligation and puncture (CLP) in vivo, and on LPS-induced HK-2 cells in vitro. For histopathological analysis, rhein effectively attenuated the severity of renal injury. Rhein could significantly decrease concentration of BUN and SCr and level of TNF-alpha and IL-1 beta in two different mouse models of experimental sepsis. Moreover, rhein could markedly attenuate circulating leukocyte infiltration and enhance phagocytic activity of macrophages partly impaired at 12 h after CLP. Rhein could enhance cell viability and suppresse the release of MCP-1 and IL-8 in LPS-stimulated HK-2 cells Furthermore, rhein down regulated the expression of phosphorylated NF-kappa B p65, I kappa B alpha and IKK beta stimulated by LPS both in vivo and in vitro. All these results suggest that rhein has protective effects on endotoxin-induced kidney injury. The underlying mechanism of rhein on anti-endotoxin kidney injury may be closely related with its antiinflammatory and immunomodulatory properties by decreasing NF-kappa B activation through restraining the expression and phosphorylation of the relevant proteins in NF-kappa B signal pathway, hindering transcription of NF-kappa B p65. These evidence suggest that rhein has a potential application to treat endotoxemia-associated acute kidney injury.