Liver nitrosation and inflammation in septic rats were suppressed by propofol via downregulating TLR4/NF-κB-mediated iNOS and IL-6 gene expressions

Gong Jhe Wu, Yung Wei Lin, Chi Yuan Chuang, Hsiao Chien Tsai, Ruei Ming Chen

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Aims: Propofol can be applied as an anesthetic or sedative agent for septic patients. Our previous studies showed that propofol ameliorated inflammation- and nitrosative stress-induced cellular insults. This study further evaluated effects of propofol on cecal ligation and puncture (CLP)-induced septic insults to rats and its possible mechanisms. Main methods: Wistar rats were administered with CLP and effects of propofol on CLP-induced liver dysfunction and rat death were evaluated. Levels of hepatic or systemic nitrogen oxides (NOx) and interleukin (IL)-6 were quantified. Sequentially, inducible nitric oxide synthase (iNOS) and IL-6 gene expressions, toll-like receptor 4 (TLR4) protein levels, and nuclear factor (NF)-κB translocation were determined. Key findings: Subjecting rats to CLP led to body weight loss, liver weight gain, and death. Administration of propofol lessened CLP-induced augmentations of serum and hepatic nitrosative stress and IL-6 levels. Additionally, propofol suppressed CLP-induced enhancements in levels of hepatic iNOS protein. Furthermore, the CLP-induced iNOS and IL-6 mRNA expressions in the liver were inhibited following propofol administration. Sequentially, subjecting rats to CLP enhanced hepatic TLR4 protein levels and NF-κB translocation to nuclei, but propofol inhibited these augmentations. Significance: Consequently, exposure to propofol protected against CLP-induced liver dysfunction and increased the survival rates of the animals. This study shows that propofol can protect rats against septic insults through suppression of systemic and hepatic nitrosative and inflammatory stress due to inhibition of TLR4/NF-κB-mediated iNOS and IL-6 mRNA and protein expressions.

Original languageEnglish
Pages (from-to)25-32
Number of pages8
JournalLife Sciences
Volume195
DOIs
Publication statusPublished - Feb 15 2018

Keywords

  • IL-6
  • iNOS
  • Nitrosative/inflammatory stress
  • Propofol
  • Sepsis
  • TLR4/NF-κB
  • Actins/metabolism
  • Rats, Wistar
  • Sepsis/drug therapy
  • Toll-Like Receptor 4/drug effects
  • Male
  • Liver/metabolism
  • Translocation, Genetic/drug effects
  • Hepatitis/drug therapy
  • Propofol/therapeutic use
  • NF-kappa B/drug effects
  • Gene Expression Regulation/drug effects
  • Nitrosation/drug effects
  • Interleukin-6/biosynthesis
  • Nitric Oxide Synthase Type II/biosynthesis
  • Down-Regulation
  • Rats
  • Cecal Diseases/metabolism
  • Animals
  • Hypnotics and Sedatives/therapeutic use

ASJC Scopus subject areas

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

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