Abstract
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-α and IL-1β 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-κB p65, IκBα and IKKβ 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 anti-inflammatory and immunomodulatory properties by decreasing NF-κB activation through restraining the expression and phosphorylation of the relevant proteins in NF-κB signal pathway, hindering transcription of NF-κB p65.These evidence suggest that rhein has a potential application to treat endotoxemia-associated acute kidney injury.
Highlights
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
Previous studies demonstrated that during sepsis, repeated stimulation of the kidneys led to the production of a large number of pro-inflammatory cytokines including tumor necrosis factor (TNF) -α, interleukin (IL) -6 through nuclear factor-κ appa B (NF-κ B) signaling pathway, which is a key regulator in keeping homeostasis of immune system and a major drug target in a variety of diseases[12,13,14]
While only rhein treatment has no significant effect on Blood Urea Nitrogen (BUN) and Serum Creatinine Determination (SCr) levels, these results indicate that rhein has a protective effect on CLP-induced Acute kidney injury (AKI) without nephrotoxicity at high doses
Summary
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. Rhein could enhance cell viability and suppresse the release of MCP-1 and IL-8 in LPS-stimulated HK-2 cells rhein down regulated the expression of phosphorylated NF-κB p65, IκBα and IKKβ stimulated by LPS both in vivo and in vitro All these results suggest that rhein has protective effects on endotoxin-induced kidney injury. We designed and performed experiments to investigate the effect and mechanism of rhein on sepsis-induced AKI in two different in vivo and in vitro models. This study presented new insights into mechanisms of rhein against AKI and provided pharmacological evidence for clinical applications
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