Propofol reduces liver dysfunction caused by tumor necrosis factor-α production in Kupffer cells

The present study, conducted in rats, investigated whether propofol attenuates lipopolysaccharide (LPS)-triggered liver dysfunction via regulation of tumor necrosis factor (TNF)-alpha production in activated Kupffer cells. Rats received LPS (500 mu g/kg) under Urethane (TM) sedation (1 g/kg) in combination with propofol (5 mg/kg/h) or Intralipid (TM) 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-alpha 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-alpha in Kupffer cells. ALT and AST serum levels increased approximately four-fold in LPS-exposed rats compared with Intralipid (TM)-treated rats at 6 h after LPS administration, whereas propofol and GdCl3 reduced the LPS-induced increases. LPS simultaneously augmented TNF-alpha expression in Kupffer cells, followed by increased caspase-3 activity and apoptosis in hepatocytes. Immunofluorescence staining and immunoblotting assay showed that TNF-alpha 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-alpha production in activated Kupffer cells. These results suggest that propofol is capable of inhibiting inflammation-induced liver dysfunction in vivo.