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

Jiazheng Li, Nobuhisa Kandatsu, Guo Gang Feng, Jia Zhen Jiang, Lei Huang, Hiroyuki Kinoshita, Shoshiro Okada, Yoshihiro Fujiwara

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Purpose: 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. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish
Pages (from-to)420-426
Number of pages7
JournalJournal of Anesthesia
Volume30
Issue number3
DOIs
Publication statusPublished - 01-06-2016
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Anesthesiology and Pain Medicine

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