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16.02.2016 | Original Article

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

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

Erschienen in: Journal of Anesthesia | Ausgabe 3/2016

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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.

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Titel: Propofol reduces liver dysfunction caused by tumor necrosis factor-α production in Kupffer cells
verfasst von: Jiazheng Li
Nobuhisa Kandatsu
Guo-Gang Feng
Jia-Zhen Jiang
Lei Huang
Hiroyuki Kinoshita
Shoshiro Okada
Yoshihiro Fujiwara
Publikationsdatum: 16.02.2016
Verlag: Springer Japan
Erschienen in: Journal of Anesthesia / Ausgabe 3/2016
Print ISSN: 0913-8668
Elektronische ISSN: 1438-8359
DOI: https://doi.org/10.1007/s00540-016-2145-x

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