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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 TNF-α (A) and IL-1β (B) levels after CLP challenge. Quantitation of TNF-α and IL-1β in renal tissue was performed by ELISA. Data are represented as mean ± SD of 10 animals of each group. ###p < 0.001 compared to sham group; *p < 0.05, **p < 0.01 and ***p < 0.001 compared to CLP group.
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f8: Effects of rhein on TNF-α (A) and IL-1β (B) levels after CLP challenge. Quantitation of TNF-α and IL-1β in renal tissue was performed by ELISA. Data are represented as mean ± SD of 10 animals of each group. ###p < 0.001 compared to sham group; *p < 0.05, **p < 0.01 and ***p < 0.001 compared to CLP group.

Mentions: The increase of pro-inflammatory cytokines and reduction of circulatory white blood cell (WBC) count are typical signs of pro-inflammatory response and onset of sepsis. In our study, pro-inflammatory cytokines (TNF-α and IL-1β) and WBC count were detected for the evaluation of the severity of sepsis in each group. The results showed that the levels of TNF-α and IL-1β in kidney were low and comparable in sham mice treated with either vehicle or rhein. By contrast, a dramatic increase levels of TNF-α and IL-1β were observed in CLP group 12 h after the surgery. The elevated levels of TNF-α and IL-1β were significantly inhibited by treatment with rhein (Fig. 8). As shown in Fig. 9, peripheral WBC count at 12 h after CLP surgery was significantly decreased. Rhein significantly increased total leukocyte number ,and the following differential count showed that both monocytes and neutrophil counts were significantly increased after rhein treatment, while rhein treatment only in sham mice did not alter the WBC level.


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 TNF-α (A) and IL-1β (B) levels after CLP challenge. Quantitation of TNF-α and IL-1β in renal tissue was performed by ELISA. Data are represented as mean ± SD of 10 animals of each group. ###p < 0.001 compared to sham group; *p < 0.05, **p < 0.01 and ***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

f8: Effects of rhein on TNF-α (A) and IL-1β (B) levels after CLP challenge. Quantitation of TNF-α and IL-1β in renal tissue was performed by ELISA. Data are represented as mean ± SD of 10 animals of each group. ###p < 0.001 compared to sham group; *p < 0.05, **p < 0.01 and ***p < 0.001 compared to CLP group.
Mentions: The increase of pro-inflammatory cytokines and reduction of circulatory white blood cell (WBC) count are typical signs of pro-inflammatory response and onset of sepsis. In our study, pro-inflammatory cytokines (TNF-α and IL-1β) and WBC count were detected for the evaluation of the severity of sepsis in each group. The results showed that the levels of TNF-α and IL-1β in kidney were low and comparable in sham mice treated with either vehicle or rhein. By contrast, a dramatic increase levels of TNF-α and IL-1β were observed in CLP group 12 h after the surgery. The elevated levels of TNF-α and IL-1β were significantly inhibited by treatment with rhein (Fig. 8). As shown in Fig. 9, peripheral WBC count at 12 h after CLP surgery was significantly decreased. Rhein significantly increased total leukocyte number ,and the following differential count showed that both monocytes and neutrophil counts were significantly increased after rhein treatment, while rhein treatment only in sham mice did not alter the WBC level.

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