Propofol increases bone morphogenetic protein-7 and decreases oxidative stress in sepsis-induced acute kidney injury

Chung-Hsi Hsing, Willy Chou, Jhi Joung Wang, Hung Wei Chen, Ching Hua Yeh

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35 Citations (Scopus)

Abstract

Background. Pro-inflammatory cytokines and free radicals damage renal tissue leading to acute kidney injury (AKI) during sepsis. Bone morphogenetic protein-7 (BMP-7) represses tumour necrosis factor (TNF)-α-induced inflammatory responses and protects kidney from injury. The sedative agent, propofol, has immunomodulatory and antioxidative properties. The present study investigated whether propofol could reduce AKI in caecal ligation and puncture (CLP) mice and the possible mechanism behind this.Methods. Mice were treated with propofol or saline immediately and 12 h after CLP surgery. Kidney injury, survival and cytokine expressions of CLP mice were observed 24 h after CLP surgery. In vitro, lipopolysaccharide (LPS)-stimulated rat mesangial cells (RMCs) or hydrogen peroxide (H2O2)-exposed murine kidney epithelial cells (M1) were treated with propofol. The expression of BMP-7, TNF-α and monocyte chemotactic protein (MCP)-1 in CLP mice kidney, RMCs or M1 cells was determined by RTPCR. Free radical generation and cell death of RMCs and M1 cells were analysed. Nuclear factor (NF)-κB and peroxisome proliferator-activated receptor (PPAR)-γ expressions in LPS-stimulated RMCs were determined by western blotting.Results. Propofol increased survival and ameliorated AKI in CLP mice. Propofol increased BMP-7 expression but decreased TNF-α and MCP-1 expressions in the kidney of CLP mice and LPS-stimulated RMCs. Propofol also inhibited free radical generation and cell death in LPS-stimulated RMCs and decreased the TNF-α expression and cell death in H2O2-exposed M1 cells. Moreover, propofol decreased NF-κB but increased PPAR-γ expression in LPS-stimulated RMCs.Conclusions. Propofol treatment could protect kidney from sepsis-induced AKI by increasing BMP-7 expression, decreasing inflammatory cytokines and inhibiting oxidative stress.

Original languageEnglish
Pages (from-to)1162-1172
Number of pages11
JournalNephrology Dialysis Transplantation
Volume26
Issue number4
DOIs
Publication statusPublished - Apr 2011

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Keywords

  • acute kidney injury
  • bone morphogenetic protein-7
  • oxidative stress
  • propofol
  • sepsis

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

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