Exogenous carbon monoxide suppresses Escherichia coli vitality and improves survival in an Escherichia coli-induced murine sepsis model

Aim： Endogenous carbon monoxide （CO） has been shown to modulate inflammation and inhibit cytokine production both in vivo and in vitro. The aim of this study was to examine whether exogenous carbon monoxide could suppress the vitality of Escherichia coli （E coli） and improve the survival rate in an...

Full description

Saved in:
Bibliographic Details
Published in:Acta pharmacologica Sinica 2014-12, Vol.35 (12), p.1566-1576
Main Authors: Shen, Wei-chang, Wang, Xu, Qin, Wei-ting, Qiu, Xue-feng, Sun, Bing-wei
Format: Article
Language:English
Subjects:
Animals
Biomarkers - blood
Carbon Monoxide - metabolism
Cytokines - blood
Disease Models, Animal
Dose-Response Relationship, Drug
Escherichia coli
Escherichia coli - drug effects
Escherichia coli - growth & development
Escherichia coli - metabolism
Escherichia coli - pathogenicity
Escherichia coli Infections - blood
Escherichia coli Infections - drug therapy
Escherichia coli Infections - microbiology
Escherichia coli Infections - pathology
ICR小鼠
Inflammation Mediators - blood
Injections, Intravenous
Lipopolysaccharides - blood
Liver - drug effects
Liver - metabolism
Liver - microbiology
Liver - pathology
Lung - drug effects
Lung - metabolism
Lung - microbiology
Lung - pathology
Male
Mice, Inbred ICR
NF-kappa B - metabolism
Nitric Oxide Synthase Type II - genetics
Nitric Oxide Synthase Type II - metabolism
Organometallic Compounds - administration & dosage
Organometallic Compounds - metabolism
Organometallic Compounds - pharmacology
Peroxidase - metabolism
RNA, Messenger - metabolism
RT-PCR检测
Sepsis - blood
Sepsis - drug therapy
Sepsis - microbiology
Sepsis - pathology
Time Factors
内源性一氧化碳
外源性
大肠杆菌感染
模型
生存率
败血症
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Aim： Endogenous carbon monoxide （CO） has been shown to modulate inflammation and inhibit cytokine production both in vivo and in vitro. The aim of this study was to examine whether exogenous carbon monoxide could suppress the vitality of Escherichia coli （E coli） and improve the survival rate in an E coil-induced murine sepsis model. Methods： ICR mice were infected with E coli, and immediately injected intravenously with carbon monoxide releasing molecule-2 （CORM-2, 8 mg/kg） or inactive CORM-2 （8 mg=/kg）. The survival rate was monitored 6 times daily for up to 36 h. The blood samples, liver and lung tissues were collected at 6 h after the infection. Bacteria in peritoneal lavage fluid, blood and tissues were enumerated following culture. Tissue iNOS mRNA expression was detected using RT-PCR. NF-κB expression was detected with Western blotting. Results： Addition of CORM-2 （200 and 400 pmol/L） into culture medium concentration-dependently suppressed the growth of E coli and decreased the colony numbers, but inactive CORM-2 had no effect. Treatment of the infected mice with CORM-2 significantly increased the survival rate to 55%, while all the infected mice treated with inactive CORM-2 died within 36 h. E coil infection caused severe pathological changes in liver and lungs, and significantly increased serum transaminases, lipopolysaccharide, TNF-α and IL-1β levels, as well as myeloperoxidase activity, TNF-α and IL-1β levels in the major organ＇s. Meanwhile, E coli infection significantly increased the number of colonies and the expression of iNOS mRNA and NF-KB in the major organs. All these abnormalities were significantly attenuated by CORM-2 treatment, while inactive CORM-2 was ineffective. Conclusion： In addition directly suppressing E coli, CORM-2 protects the liver and lungs against E coli-induced sepsis in mice, thus improving their survival.
ISSN:1671-4083
1745-7254
DOI:10.1038/aps.2014.99