title: Propofol reduces liver dysfunction caused by tumor necrosis factor-α production in Kupffer cells.
abstract: The present study, conducted in rats, investigated whether propofol attenuates lipopolysaccharide (LPS)-triggered liver dysfunction via regulation of tumor necrosis factor (TNF)-α production in activated Kupffer cells.
  
  
  
  Rats received LPS (500 μg/kg) under Urethane™ sedation (1 g/kg) in combination with propofol (5 mg/kg/h) or Intralipid™ from 1 h before to 6 h after LPS administration. Some rats were treated with 10 mg/kg gadolinium chloride (GdCl3) to induce Kupffer cell depletion. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), TNF-α mRNA and protein expression, caspase-3 activation and apoptosis were evaluated in hepatocytes. Immunofluorescence staining revealed expression of the pan-macrophage marker CD68 as well as TNF-α in Kupffer cells.
  
  
  
  ALT and AST serum levels increased approximately four-fold in LPS-exposed rats compared with Intralipid™-treated rats at 6 h after LPS administration, whereas propofol and GdCl3 reduced the LPS-induced increases. LPS simultaneously augmented TNF-α expression in Kupffer cells, followed by increased caspase-3 activity and apoptosis in hepatocytes. Immunofluorescence staining and immunoblotting assay showed that TNF-α expression in Kupffer cells was inhibited by propofol and GdCl3, resulting in a reduction of caspase-3 activity and apoptosis in LPS-treated rat hepatocytes.
  
  
  
  Propofol (5 mg/kg/h) attenuated LPS-triggered liver dysfunction via inhibition of TNF-α production in activated Kupffer cells. These results suggest that propofol is capable of inhibiting inflammation-induced liver dysfunction in vivo.
authors.affiliation: Department of Anesthesiology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
authors.forename: Jiazheng
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Kandatsu
authors.affiliation: Department of Pharmacology, Aichi Medical University School of Medicine, 1-1 Karimata Yazako, Nagakute, Aichi, 480-1195, Japan. fenggg@aichi-med-u.ac.jp.
authors.forename: Guo-Gang
authors.initials: GG
authors.lastname: Feng
authors.affiliation: Department of Anesthesiology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
authors.forename: Jia-Zhen
authors.initials: JZ
authors.lastname: Jiang
authors.affiliation: Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Anesthesiology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kinoshita
authors.affiliation: Department of Pharmacology, Aichi Medical University School of Medicine, 1-1 Karimata Yazako, Nagakute, Aichi, 480-1195, Japan.
authors.forename: Shoshiro
authors.initials: S
authors.lastname: Okada
authors.affiliation: Department of Anesthesiology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujiwara
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D053148:Caspase 3 / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology; D005682:Gadolinium / Q000633:toxicity; D007728:Kupffer Cells; D008111:Liver Function Tests; D008297:Male; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D000097382:CD68 Molecule
chemical_list: D000410:Alanine Transaminase; D018686:Anesthetics, Intravenous; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001219:Aspartate Aminotransferases; D053148:Caspase 3; D005217:Fat Emulsions, Intravenous; D005682:Gadolinium; D015742:Propofol; D014409:Tumor Necrosis Factor-alpha; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C038958:gadolinium chloride
keywords: Kupffer cells; Lipopolysaccharide; Liver injury; Propofol; Tumor necrosis factor-α