Low dose of carbon monoxide intraperitoneal injection provides potent protection against GalN/LPS-induced acute liver injury in mice

Authors

  • Zongmei Wen,

    1. Department of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China
    2. Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China
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    • Zongmei Wen and Yan Liu contributed equally to this work.

  • Yan Liu,

    1. Department of Liver Diseases, Beijing Youan Hospital affiliated with Capital Medical University, Beijing, People's Republic of China
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    • Zongmei Wen and Yan Liu contributed equally to this work.

  • Feng Li,

    Corresponding author
    1. Department of Surgery, Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA
    • Correspondence to: Tao Wen, Department of Liver Diseases, Beijing Youan Hospital affiliated with Capital Medical University, Beijing 100069, People's Republic of China. E-mail: wentao528@gmail.com

      Feng Li, Department of Surgery, Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA. E-mail: fengli6870@gmail.com

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  • Tao Wen

    Corresponding author
    1. Department of Liver Diseases, Beijing Youan Hospital affiliated with Capital Medical University, Beijing, People's Republic of China
    • Correspondence to: Tao Wen, Department of Liver Diseases, Beijing Youan Hospital affiliated with Capital Medical University, Beijing 100069, People's Republic of China. E-mail: wentao528@gmail.com

      Feng Li, Department of Surgery, Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA. E-mail: fengli6870@gmail.com

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ABSTRACT

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.

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