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

Yu C, Qi D, Sun JF, Li P, Fan HY - Sci Rep (2015)

Bottom Line: 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.All these results suggest that rhein has protective effects on endotoxin-induced kidney injury.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Binzhou Medical University, Yantai, Shandong, China.

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.

No MeSH data available.


Related in: MedlinePlus

Effects of rhein on serum BUN (A) and SCr(B) in CLP model. Data are represented as mean ± SD of 10 animals of each group. ###p < 0.001 compared to sham group; **p < 0.01, ***p < 0.001 compared to CLP group.
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f7: Effects of rhein on serum BUN (A) and SCr(B) in CLP model. Data are represented as mean ± SD of 10 animals of each group. ###p < 0.001 compared to sham group; **p < 0.01, ***p < 0.001 compared to CLP group.

Mentions: To further investigate the effect of rhein on AKI induced by polymicrobial sepsis, we established murine CLP model. BUN and SCr were determined to analyze kidney function. As shown in Fig. 7, CLP induced significant increases in both BUN and SCr levels compared with sham group. The increases were significantly attenuated by treatment with rhein. While only rhein treatment has no significant effect on BUN and SCr levels, these results indicate that rhein has a protective effect on CLP-induced AKI without nephrotoxicity at high doses.


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

Yu C, Qi D, Sun JF, Li P, Fan HY - Sci Rep (2015)

Effects of rhein on serum BUN (A) and SCr(B) in CLP model. Data are represented as mean ± SD of 10 animals of each group. ###p < 0.001 compared to sham group; **p < 0.01, ***p < 0.001 compared to CLP group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493574&req=5

f7: Effects of rhein on serum BUN (A) and SCr(B) in CLP model. Data are represented as mean ± SD of 10 animals of each group. ###p < 0.001 compared to sham group; **p < 0.01, ***p < 0.001 compared to CLP group.
Mentions: To further investigate the effect of rhein on AKI induced by polymicrobial sepsis, we established murine CLP model. BUN and SCr were determined to analyze kidney function. As shown in Fig. 7, CLP induced significant increases in both BUN and SCr levels compared with sham group. The increases were significantly attenuated by treatment with rhein. While only rhein treatment has no significant effect on BUN and SCr levels, these results indicate that rhein has a protective effect on CLP-induced AKI without nephrotoxicity at high doses.

Bottom Line: 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.All these results suggest that rhein has protective effects on endotoxin-induced kidney injury.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Binzhou Medical University, Yantai, Shandong, China.

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.

No MeSH data available.


Related in: MedlinePlus