Chronic Lithium Treatment Protects Against Liver Ischemia/Reperfusion Injury in Rats

Authors

  • Anding Liu,

    Corresponding author
    1. Experimental Transplantation Surgery, Department of General, Visceral, and Vascular Surgery, Friedrich Schiller University of Jena, Jena, Germany
    • Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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    • These authors contributed equally to this work.

  • Haoshu Fang,

    1. Experimental Transplantation Surgery, Department of General, Visceral, and Vascular Surgery, Friedrich Schiller University of Jena, Jena, Germany
    2. Department of Pathophysiology, Anhui Medical University, Hefei, China
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  • Uta Dahmen,

    1. Experimental Transplantation Surgery, Department of General, Visceral, and Vascular Surgery, Friedrich Schiller University of Jena, Jena, Germany
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  • Olaf Dirsch

    1. Institute for Pathology, University Hospital of Jena, Jena, Germany
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  • This project was supported by the German Federal Ministry for Education and Research (BMBF) Virtual Liver Network.

Address reprint requests to Uta Dahmen, M.D., Experimental Transplantation Surgery, Department of General, Visceral, and Vascular Surgery, Friedrich Schiller University of Jena, Drackendorfer Straße 1, 07747 Jena, Germany. Telephone: +49-03641-932 5350; FAX: +49-03641-932 5352; E-mail: uta.dahmen@med.uni-jena.de

Abstract

Lithium has long been widely used in the treatment of bipolar mood disorders. Recent studies have demonstrated that lithium is able to decrease ischemia/reperfusion (I/R) injury in the brain, kidneys, and heart. Because lithium may act on a number of stress and survival pathways, it is of great interest to explore this compound also in the setting of liver I/R injury. In this study, we aimed to evaluate the effects of lithium in a model of liver I/R injury in rats. Chronic treatment with lithium (2 mmol/kg for 3 days before ischemia) decreased I/R injury, whereas acute treatment with a single dose of lithium (2 mmol/kg 1 hour before ischemia) did not confer any protection in a partial hepatic I/R model. Furthermore, rats subjected to chronic lithium treatment had a significantly better survival rate (60%) than saline-treated rats (27%) in a total hepatic I/R survival model. Chronic lithium treatment protected against liver I/R injury, as indicated by lower serum aminotransferase levels, fewer I/R-associated histopathological changes, lower hepatic inflammatory cytokine levels, less neutrophil infiltration, and lower hepatic high-mobility group box expression and serum levels. The mechanism of action of lithium appears to involve its ability to inhibit glycogen synthase kinase 3β activation, modulate mitogen-activated protein kinase activation, inhibit hepatic apoptosis, and induce autophagy. On the basis of these data, we conclude that lithium treatment may be a simple and applicable preconditioning intervention for protecting against liver I/R injury. Liver Transpl 19:762–772, 2013.. © 2013 AASLD.

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