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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

Effect of rhein on phospho-NF-κB p65 localization and expression in AKI by immunohistochemistry (magnification × 400).(A) Control group; (B) LPS group; (C) Rhein (20 mg/kg) + LPS group; (D)Rhein (40 mg/kg) + LPS group. (E) Rhein (80 mg/kg) + LPS group. (F) IOD values of phospho-NF-κB p65 staining. Data are represented as mean ± SD of 5 animals of each group, ### P < 0.001 versus control group; **p < 0.01 and ***P < 0.001 versus LPS group.
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f5: Effect of rhein on phospho-NF-κB p65 localization and expression in AKI by immunohistochemistry (magnification × 400).(A) Control group; (B) LPS group; (C) Rhein (20 mg/kg) + LPS group; (D)Rhein (40 mg/kg) + LPS group. (E) Rhein (80 mg/kg) + LPS group. (F) IOD values of phospho-NF-κB p65 staining. Data are represented as mean ± SD of 5 animals of each group, ### P < 0.001 versus control group; **p < 0.01 and ***P < 0.001 versus LPS group.

Mentions: To gain a better insight into the potential mechanisms underlying the observed beneficial effects of rhein on the sepsis-associated AKI, we investigated the effects of this compound on NF-κB signaling pathways in the kidneys of mice. Immunostaining for phosphorylated NF-κB p65 demonstrated its expression and localization in kidney sections. Staining for phosphorylated NF-κB p65 in nuclei and cytoplasm of proximal convoluted tubule and renal glomerulus was more pronounced in LPS-induced group mice than in control mice. As shown in Fig. 5, rhein administration attenuated the phosphorylated NF-κB p65 staining.


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)

Effect of rhein on phospho-NF-κB p65 localization and expression in AKI by immunohistochemistry (magnification × 400).(A) Control group; (B) LPS group; (C) Rhein (20 mg/kg) + LPS group; (D)Rhein (40 mg/kg) + LPS group. (E) Rhein (80 mg/kg) + LPS group. (F) IOD values of phospho-NF-κB p65 staining. Data are represented as mean ± SD of 5 animals of each group, ### P < 0.001 versus control group; **p < 0.01 and ***P < 0.001 versus LPS group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f5: Effect of rhein on phospho-NF-κB p65 localization and expression in AKI by immunohistochemistry (magnification × 400).(A) Control group; (B) LPS group; (C) Rhein (20 mg/kg) + LPS group; (D)Rhein (40 mg/kg) + LPS group. (E) Rhein (80 mg/kg) + LPS group. (F) IOD values of phospho-NF-κB p65 staining. Data are represented as mean ± SD of 5 animals of each group, ### P < 0.001 versus control group; **p < 0.01 and ***P < 0.001 versus LPS group.
Mentions: To gain a better insight into the potential mechanisms underlying the observed beneficial effects of rhein on the sepsis-associated AKI, we investigated the effects of this compound on NF-κB signaling pathways in the kidneys of mice. Immunostaining for phosphorylated NF-κB p65 demonstrated its expression and localization in kidney sections. Staining for phosphorylated NF-κB p65 in nuclei and cytoplasm of proximal convoluted tubule and renal glomerulus was more pronounced in LPS-induced group mice than in control mice. As shown in Fig. 5, rhein administration attenuated the phosphorylated NF-κB p65 staining.

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