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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 kidney injury after LPS administration.Representative histological changes in kidneys obtained from mice of different groups (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.The sections shown were harvested 12 h after LPS injection and stained with H&E. Magnification: ×400. (F)Pathological score of representative kidney samples of each group. 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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f2: Effect of rhein on kidney injury after LPS administration.Representative histological changes in kidneys obtained from mice of different groups (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.The sections shown were harvested 12 h after LPS injection and stained with H&E. Magnification: ×400. (F)Pathological score of representative kidney samples of each group. 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: Histopathological change is a direct indication of renal injury. The H&E-stained renal tissues appeared to have normal kidney tubules in the control group samples (Fig. 2A). In contrast, it was demonstrated that LPS-induced histopathological changes in the renal tissues, such as the edema of renal tubular epithelial cells, glomerular atrophy, dilation of renal capsule cavity, destruction of tubular structures, the epithelial cells of the local focal necrosis collapse, renal interstitial edema of epithelial cells (Fig. 2B). However, pretreatment with rhein (20, 40 and 80 mg/kg mg/kg) significantly diminished LPS-induced epithelial atrophy and necrosis and interstitial edema to varying degrees (Fig. 2C–E). There was a significantly reduced in the score of kidney pathological damage (Fig. 2F).


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 kidney injury after LPS administration.Representative histological changes in kidneys obtained from mice of different groups (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.The sections shown were harvested 12 h after LPS injection and stained with H&E. Magnification: ×400. (F)Pathological score of representative kidney samples of each group. 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

f2: Effect of rhein on kidney injury after LPS administration.Representative histological changes in kidneys obtained from mice of different groups (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.The sections shown were harvested 12 h after LPS injection and stained with H&E. Magnification: ×400. (F)Pathological score of representative kidney samples of each group. 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: Histopathological change is a direct indication of renal injury. The H&E-stained renal tissues appeared to have normal kidney tubules in the control group samples (Fig. 2A). In contrast, it was demonstrated that LPS-induced histopathological changes in the renal tissues, such as the edema of renal tubular epithelial cells, glomerular atrophy, dilation of renal capsule cavity, destruction of tubular structures, the epithelial cells of the local focal necrosis collapse, renal interstitial edema of epithelial cells (Fig. 2B). However, pretreatment with rhein (20, 40 and 80 mg/kg mg/kg) significantly diminished LPS-induced epithelial atrophy and necrosis and interstitial edema to varying degrees (Fig. 2C–E). There was a significantly reduced in the score of kidney pathological damage (Fig. 2F).

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