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

研究成果: 雜誌貢獻文章

6 引文 (Scopus)

摘要

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.
原文英語
頁(從 - 到)25-32
頁數8
期刊Life Sciences
195
DOIs
出版狀態已發佈 - 二月 15 2018

指紋

Nitrosation
Toll-Like Receptor 4
Propofol
Nitric Oxide Synthase Type II
Gene expression
Liver
Punctures
Rats
Interleukin-6
Ligation
Down-Regulation
Inflammation
Gene Expression
Nuclear Proteins
Liver Diseases
Proteins
Nitrogen Oxides
Messenger RNA
Proxy
Hypnotics and Sedatives

ASJC Scopus subject areas

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

引用此文

@article{b46538efc13a411982202d7a8ee42141,
title = "Liver nitrosation and inflammation in septic rats were suppressed by propofol via downregulating TLR4/NF-κB-mediated iNOS and IL-6 gene expressions",
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.",
keywords = "IL-6, iNOS, Nitrosative/inflammatory stress, Propofol, Sepsis, TLR4/NF-κB",
author = "Wu, {Gong Jhe} and Lin, {Yung Wei} and Chuang, {Chi Yuan} and Tsai, {Hsiao Chien} and Chen, {Ruei Ming}",
year = "2018",
month = "2",
day = "15",
doi = "10.1016/j.lfs.2018.01.005",
language = "English",
volume = "195",
pages = "25--32",
journal = "Life Sciences",
issn = "0024-3205",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Liver nitrosation and inflammation in septic rats were suppressed by propofol via downregulating TLR4/NF-κB-mediated iNOS and IL-6 gene expressions

AU - Wu, Gong Jhe

AU - Lin, Yung Wei

AU - Chuang, Chi Yuan

AU - Tsai, Hsiao Chien

AU - Chen, Ruei Ming

PY - 2018/2/15

Y1 - 2018/2/15

N2 - 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.

AB - 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.

KW - IL-6

KW - iNOS

KW - Nitrosative/inflammatory stress

KW - Propofol

KW - Sepsis

KW - TLR4/NF-κB

UR - http://www.scopus.com/inward/record.url?scp=85041696172&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041696172&partnerID=8YFLogxK

U2 - 10.1016/j.lfs.2018.01.005

DO - 10.1016/j.lfs.2018.01.005

M3 - Article

C2 - 29307523

AN - SCOPUS:85041696172

VL - 195

SP - 25

EP - 32

JO - Life Sciences

JF - Life Sciences

SN - 0024-3205

ER -