Panaxadiol Saponin and Dexamethasone Improve Renal Function in Lipopolysaccharide-Induced Mouse Model of Acute Kidney Injury.

Yan Chen,Xiaoqin Wang,Yuan Fang,Xuejian Zhao,Guang Yang,Yanwei Du,Yan Meng,Pin Gao,Yang Li,Jian Fu

doi:10.1371/journal.pone.0134653

Abstract

BackgroundAcute kidney injury (AKI) is a serious complication of systemic inflammatory response syndrome (SIRS), which has a high mortality rate. Previous studies showed that panaxadiol saponin (PDS) and Dexamethasone have similar anti-inflammatory properties and protect cardiopulmonary function in lipopolysaccharide (LPS)-induced septic shock rats. In the present study, we investigated whether PDS or Dexamethasone has a similar role in improving kidney function in LPS-induced AKI mice.Methods and ResultsMice subjected to LPS (10 mg/kg) treatment exhibited AKI demonstrated by markedly increased blood urea nitrogen and creatinine levels compared with controls (P<0.01). However, PDS and Dexamethasone induce similar reverse effects on renal function, such as reduced serum creatinine and blood urea nitrogen levels compared with the LPS group (P<0.05). PDS decreased the production and release of tumor necrosis factor (TNF)-α and interleukin (IL)-6 by inhibiting the NF-κB signaling pathway, down-regulating inducible nitric oxide synthase protein expression levels and inhibiting oxidative stress. In most anti-AKI mechanisms, PDS and dexamethasone were similar, but PDS are better at inhibition of TNF production, promote SOD activity and inhibition of IKB phosphorylation. In addition, nuclear glucocorticoid receptor expression was markedly enhanced in PDS and Dexamethasone treatment groups. Further research is required to determine whether PDS can combine with the glucocorticoid receptor to enter the nucleus.ConclusionThis study demonstrated that PDS and dexamethasone have similar reverse amelioration for renal functions, and have potential application prospects in the treatment of sepsis-induced AKI.

Highlights

Renal failure during gram negative sepsis can be profound, difficult to treat and fatal [1]
Mice subjected to LPS (10 mg/kg) treatment exhibited Acute kidney injury (AKI) demonstrated by markedly increased blood urea nitrogen and creatinine levels compared with controls (P
panaxadiol saponin (PDS) and Dexamethasone induce similar reverse effects on renal function, such as reduced serum creatinine and blood urea nitrogen levels compared with the LPS group (P

Summary

Introduction

Renal failure during gram negative sepsis can be profound, difficult to treat and fatal [1]. Acute kidney injury (AKI) occurs during endotoxemia, where endotoxin binds to endothelium and leukocytes, inducing the production and release of cytokines and a systemic “cytokine storm”, namely systemic inflammatory response syndrome (SIRS). This is accompanied by decreased peripheral vascular resistance and hypotension leading to septic shock [1, 2, 3]. Studies have shown that renal damage in experimental septic AKI is potentially reversible, at least as inferred from the benefits afforded by early interventions that restore renal function Such interventions include volume replacement, free radical scavengers and anti-inflammatory therapies [2, 4]. We investigated whether PDS or Dexamethasone has a similar role in improving kidney function in LPS-induced AKI mice

Methods

Results

Conclusion