Propofol increases bone morphogenetic protein-7 and decreases oxidative stress in sepsis-induced acute kidney injury.
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 (H(2)O(2))-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 RT-PCR. 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 H(2)O(2)-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.
Hsing
Chung-Hsi
CH
Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan.
Chou
Willy
W
Wang
Jhi-Joung
JJ
Chen
Hung-Wei
HW
Yeh
Ching-Hua
CH
D058186:Acute Kidney Injury / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics / Q000378:metabolism*; D002432:Cecum; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000627:therapeutic use; D008026:Ligation; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D050527:Mesangial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D015742:Propofol / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000150:complications*; D013481:Superoxides / Q000378:metabolism; D015996:Survival Rate
D055419:Bone Morphogenetic Protein 7; D016207:Cytokines; D006993:Hypnotics and Sedatives; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D013481:Superoxides; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D015742:Propofol