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

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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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Acknowledgments

This work was supported in part by a Grant-in-Aid for Scientific Research (No. 23592689), a grant from the Strategic Research Foundation Grant-aided Project for Private Universities (S1101027) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan (MEXT), JSPS KAKENHI Grant Number 15K10998, and a grant for Education and Research from the Aikeikai Foundation, Japan.

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Authors and Affiliations

  1. Department of Anesthesiology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan

    Jiazheng Li, Nobuhisa Kandatsu, Jia-Zhen Jiang, Hiroyuki Kinoshita & Yoshihiro Fujiwara

  2. Department of Pharmacology, Aichi Medical University School of Medicine, 1-1 Karimata Yazako, Nagakute, Aichi, 480-1195, Japan

    Guo-Gang Feng & Shoshiro Okada

  3. Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, China

    Lei Huang

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  1. Jiazheng Li
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  2. Nobuhisa Kandatsu
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Correspondence to Guo-Gang Feng.

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Li, J., Kandatsu, N., Feng, GG. et al. Propofol reduces liver dysfunction caused by tumor necrosis factor-α production in Kupffer cells. J Anesth 30, 420–426 (2016). https://doi.org/10.1007/s00540-016-2145-x

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  • DOI: https://doi.org/10.1007/s00540-016-2145-x

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