Zongmei Wen and Yan Liu contributed equally to this work.
Low dose of carbon monoxide intraperitoneal injection provides potent protection against GalN/LPS-induced acute liver injury in mice
Version of Record online: 27 SEP 2012
Copyright © 2012 John Wiley & Sons, Ltd.
Journal of Applied Toxicology
Volume 33, Issue 12, pages 1424–1432, December 2013
How to Cite
Wen, Z., Liu, Y., Li, F. and Wen, T. (2013), Low dose of carbon monoxide intraperitoneal injection provides potent protection against GalN/LPS-induced acute liver injury in mice. J. Appl. Toxicol., 33: 1424–1432. doi: 10.1002/jat.2806
- Issue online: 22 OCT 2013
- Version of Record online: 27 SEP 2012
- Manuscript Accepted: 27 JUN 2012
- Manuscript Revised: 24 JUN 2012
- Manuscript Received: 27 MAY 2012
- Capital Medical University Basic & Clinical Collaborative Project. Grant Number: 12JL14
- carbon monoxide;
- liver injury;
- oxidative stress;
- hepatocyte apoptosis;
Carbon monoxide (CO) is an important effector-signaling molecule involved in various pathophysiological processes. Here we investigated the protective effects of exogenous CO in a murine model of acute liver damage induced by d-galactosamine (GalN) and lipopolysaccharide (LPS). Exogenous CO gas was administered to mice via intraperitoneal injection (first at a dose of 15 ml kg−1 and then, 6 h later, 8 ml kg−1), which caused a significant elevation of blood carboxyhemoglobin levels of up to 12–14% for more than 12 h. GalN/LPS were given to induce acute liver damage in mice 30 min prior to CO exposure. This showed that GalN/LPS induced severe liver injury in mice, whereas CO injection remarkably improved the survival rate of mice and led to attenuated hepatocellular damage. CO exhibited anti-oxidative capabilities by inhibiting hepatic malondialdehyde contents and restoring superoxide dismutase and glutathione, as well as by reducing inducible NOS/NO production. The anti-apoptotic and anti-inflammatory effects of CO were substantial, characterized by a notable inhibition of hepatocyte apoptosis and a reduction of pro-inflammatory cytokines in mice. Our findings thus supported the hypothesis that exogenous CO provides protective effects against acute liver damage in mice, mainly dependent on its anti-oxidative, anti-inflammatory and anti-apoptotic properties. Copyright © 2012 John Wiley & Sons, Ltd.