@article{APS4525,
author = {Wei-chang Shen and Xu Wang and Wei-ting Qin and Xue-feng Qiu and Bing-wei Sun},
title = {Exogenous carbon monoxide suppresses Escherichia coli vitality and improves survival in an Escherichia coli-induced murine sepsis model},
journal = {Acta Pharmacologica Sinica},
volume = {35},
number = {12},
year = {2016},
keywords = {},
abstract = {Wei-chang SHEN#, Xu WANG#, Wei-ting QIN, Xue-feng QIU, Bing-wei SUN*
Department of Burns and Plastic Surgery, Affiliated Hospital, Jiangsu University, Zhenjiang 212001, China
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 coli-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 μmol/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 coli 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 organs. Meanwhile, E coli infection significantly increased the number of colonies and the expression of iNOS mRNA and NF-κB 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.
Keywords: sepsis; Escherichia coli; carbon monoxide; CO-releasing molecule-2; liver; lung; cytokine; lipopolysaccharide; iNOS; NF-κB; inflammation
This study was supported by the National Natural Science Foundation of China (No 81071546, No 81272148 and No 81471903); and by the Jiangsu Natural Science Foundation, No BK2012703.
# These authors contributed equally to this work.
* To whom correspondence should be addressed.
E-mail sunbinwe@hotmail.com
Received 2014-06-10 Accepted 2014-08-20},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/4525}
}