Sepsis-induced liver dysfunction was ameliorated by propofol via suppressing hepatic lipid peroxidation, inflammation, and drug interactions

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Abstract

Aims: Our previous study showed that propofol can protect against sepsis-induced insults through suppressing liver nitrosation and inflammation. This study further evaluated the mechanisms of propofol-caused protection from sepsis-induced liver dysfunction. Main methods: Male Wistar rats were subjected to cecal ligation and puncture (CLP) and then exposed to propofol. Levels of hepatic oxidative stress and lipid peroxidation were consecutively measured. Expressions of tumor necrosis factor (TNF)-α interleukin (IL)-1β and IL-4 messenger (m)RNA or proteins were quantified. Effects of propofol on microsomal pentoxyresorufin O-dealkelase (PROD) and ethoxycoumarin O-deethylase (ECOD) activities were determined. Key findings: Administration of propofol to CLP-treated rats significantly attenuated sepsis-induced insults. CLP caused augmented serum aspartate aminotransferase and alanine aminotransferase activities and concurrently triggered liver damage. In contrast, treatment with propofol protected against CLP-induced liver dysfunction. As to the mechanisms, the CLP-induced increases in oxidative stress and lipid peroxidation levels and TNF-α and IL-1β mRNA and protein expressions were subsequently attenuated by propofol. Furthermore, administration of CLP-treated rats with propofol augmented levels of IL-4 in the liver. Phenobarbital treatment of liver microsomes in CLP-treated rats produced less amplification of PROD and ECOD activities, and a smaller amount of 4-hydroxypropofol was metabolized from propofol by liver microsomes. In contrast, more drug interactions occurred with propofol, which decreased PROD and ECOD activities in liver microsomes of CLP-treated rats. Significance: Taken together, the present study showed that propofol can protect against sepsis-induced liver dysfunction through suppressing hepatic oxidative stress, lipid peroxidation, inflammation, and drug biotransformation and interactions in the liver.

Original languageEnglish
Pages (from-to)279-286
Number of pages8
JournalLife Sciences
Volume213
DOIs
Publication statusPublished - Nov 15 2018

Fingerprint

Drug interactions
Propofol
Drug Interactions
Liver
Lipid Peroxidation
Liver Diseases
Sepsis
Punctures
Inflammation
Lipids
Ligation
7-Alkoxycoumarin O-Dealkylase
Rats
Oxidative stress
Liver Microsomes
Oxidative Stress
Interleukin-1
Interleukin-4
Tumor Necrosis Factor-alpha
Nitrosation

Keywords

  • Drug metabolism/interactions
  • Inflammation
  • Lipid peroxidation
  • Propofol
  • Septic rat

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

@article{80caec0a583d4cd091b4607d09160a5b,
title = "Sepsis-induced liver dysfunction was ameliorated by propofol via suppressing hepatic lipid peroxidation, inflammation, and drug interactions",
abstract = "Aims: Our previous study showed that propofol can protect against sepsis-induced insults through suppressing liver nitrosation and inflammation. This study further evaluated the mechanisms of propofol-caused protection from sepsis-induced liver dysfunction. Main methods: Male Wistar rats were subjected to cecal ligation and puncture (CLP) and then exposed to propofol. Levels of hepatic oxidative stress and lipid peroxidation were consecutively measured. Expressions of tumor necrosis factor (TNF)-α interleukin (IL)-1β and IL-4 messenger (m)RNA or proteins were quantified. Effects of propofol on microsomal pentoxyresorufin O-dealkelase (PROD) and ethoxycoumarin O-deethylase (ECOD) activities were determined. Key findings: Administration of propofol to CLP-treated rats significantly attenuated sepsis-induced insults. CLP caused augmented serum aspartate aminotransferase and alanine aminotransferase activities and concurrently triggered liver damage. In contrast, treatment with propofol protected against CLP-induced liver dysfunction. As to the mechanisms, the CLP-induced increases in oxidative stress and lipid peroxidation levels and TNF-α and IL-1β mRNA and protein expressions were subsequently attenuated by propofol. Furthermore, administration of CLP-treated rats with propofol augmented levels of IL-4 in the liver. Phenobarbital treatment of liver microsomes in CLP-treated rats produced less amplification of PROD and ECOD activities, and a smaller amount of 4-hydroxypropofol was metabolized from propofol by liver microsomes. In contrast, more drug interactions occurred with propofol, which decreased PROD and ECOD activities in liver microsomes of CLP-treated rats. Significance: Taken together, the present study showed that propofol can protect against sepsis-induced liver dysfunction through suppressing hepatic oxidative stress, lipid peroxidation, inflammation, and drug biotransformation and interactions in the liver.",
keywords = "Drug metabolism/interactions, Inflammation, Lipid peroxidation, Propofol, Septic rat, Drug metabolism/interactions, Inflammation, Lipid peroxidation, Propofol, Septic rat",
author = "Wu, {Gong Jhe} and Lin, {Yung Wei} and Tsai, {Hsiao Chien} and Lee, {Yuan Wen} and Chen, {Jui Tai} and Chen, {Ruei Ming}",
year = "2018",
month = "11",
day = "15",
doi = "10.1016/j.lfs.2018.10.038",
language = "English",
volume = "213",
pages = "279--286",
journal = "Life Sciences",
issn = "0024-3205",
publisher = "Elsevier Inc.",

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TY - JOUR

T1 - Sepsis-induced liver dysfunction was ameliorated by propofol via suppressing hepatic lipid peroxidation, inflammation, and drug interactions

AU - Wu, Gong Jhe

AU - Lin, Yung Wei

AU - Tsai, Hsiao Chien

AU - Lee, Yuan Wen

AU - Chen, Jui Tai

AU - Chen, Ruei Ming

PY - 2018/11/15

Y1 - 2018/11/15

N2 - Aims: Our previous study showed that propofol can protect against sepsis-induced insults through suppressing liver nitrosation and inflammation. This study further evaluated the mechanisms of propofol-caused protection from sepsis-induced liver dysfunction. Main methods: Male Wistar rats were subjected to cecal ligation and puncture (CLP) and then exposed to propofol. Levels of hepatic oxidative stress and lipid peroxidation were consecutively measured. Expressions of tumor necrosis factor (TNF)-α interleukin (IL)-1β and IL-4 messenger (m)RNA or proteins were quantified. Effects of propofol on microsomal pentoxyresorufin O-dealkelase (PROD) and ethoxycoumarin O-deethylase (ECOD) activities were determined. Key findings: Administration of propofol to CLP-treated rats significantly attenuated sepsis-induced insults. CLP caused augmented serum aspartate aminotransferase and alanine aminotransferase activities and concurrently triggered liver damage. In contrast, treatment with propofol protected against CLP-induced liver dysfunction. As to the mechanisms, the CLP-induced increases in oxidative stress and lipid peroxidation levels and TNF-α and IL-1β mRNA and protein expressions were subsequently attenuated by propofol. Furthermore, administration of CLP-treated rats with propofol augmented levels of IL-4 in the liver. Phenobarbital treatment of liver microsomes in CLP-treated rats produced less amplification of PROD and ECOD activities, and a smaller amount of 4-hydroxypropofol was metabolized from propofol by liver microsomes. In contrast, more drug interactions occurred with propofol, which decreased PROD and ECOD activities in liver microsomes of CLP-treated rats. Significance: Taken together, the present study showed that propofol can protect against sepsis-induced liver dysfunction through suppressing hepatic oxidative stress, lipid peroxidation, inflammation, and drug biotransformation and interactions in the liver.

AB - Aims: Our previous study showed that propofol can protect against sepsis-induced insults through suppressing liver nitrosation and inflammation. This study further evaluated the mechanisms of propofol-caused protection from sepsis-induced liver dysfunction. Main methods: Male Wistar rats were subjected to cecal ligation and puncture (CLP) and then exposed to propofol. Levels of hepatic oxidative stress and lipid peroxidation were consecutively measured. Expressions of tumor necrosis factor (TNF)-α interleukin (IL)-1β and IL-4 messenger (m)RNA or proteins were quantified. Effects of propofol on microsomal pentoxyresorufin O-dealkelase (PROD) and ethoxycoumarin O-deethylase (ECOD) activities were determined. Key findings: Administration of propofol to CLP-treated rats significantly attenuated sepsis-induced insults. CLP caused augmented serum aspartate aminotransferase and alanine aminotransferase activities and concurrently triggered liver damage. In contrast, treatment with propofol protected against CLP-induced liver dysfunction. As to the mechanisms, the CLP-induced increases in oxidative stress and lipid peroxidation levels and TNF-α and IL-1β mRNA and protein expressions were subsequently attenuated by propofol. Furthermore, administration of CLP-treated rats with propofol augmented levels of IL-4 in the liver. Phenobarbital treatment of liver microsomes in CLP-treated rats produced less amplification of PROD and ECOD activities, and a smaller amount of 4-hydroxypropofol was metabolized from propofol by liver microsomes. In contrast, more drug interactions occurred with propofol, which decreased PROD and ECOD activities in liver microsomes of CLP-treated rats. Significance: Taken together, the present study showed that propofol can protect against sepsis-induced liver dysfunction through suppressing hepatic oxidative stress, lipid peroxidation, inflammation, and drug biotransformation and interactions in the liver.

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KW - Inflammation

KW - Lipid peroxidation

KW - Propofol

KW - Septic rat

KW - Drug metabolism/interactions

KW - Inflammation

KW - Lipid peroxidation

KW - Propofol

KW - Septic rat

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DO - 10.1016/j.lfs.2018.10.038

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