Thyroid hormone preconditioning: Protection against ischemia-reperfusion liver injury in the rat

Authors

  • Virginia Fernández,

    1. Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile
    Search for more papers by this author
  • Iván Castillo,

    1. Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile
    Search for more papers by this author
  • Gladys Tapia,

    1. Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile
    Search for more papers by this author
  • Pamela Romanque,

    1. Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile
    2. Health Sciences Faculty, Diego Portales University, Santiago, Chile
    Search for more papers by this author
  • Sebastián Uribe-Echevarría,

    1. Experimental Surgery Laboratory, Department of Surgery, Del Salvador Hospital, Faculty of Medicine, University of Chile
    Search for more papers by this author
  • Mario Uribe,

    1. Experimental Surgery Laboratory, Department of Surgery, Del Salvador Hospital, Faculty of Medicine, University of Chile
    Search for more papers by this author
  • Denise Cartier-Ugarte,

    1. Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile
    Search for more papers by this author
  • Gonzalo Santander,

    1. Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile
    Search for more papers by this author
  • María T. Vial,

    1. Pathological Anatomy Unit, San Borja Arriarán Hospital, Santiago, Chile
    Search for more papers by this author
  • Luis A. Videla

    Corresponding author
    1. Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile
    • Programa de Farmacología Molecular y Clínica, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
    Search for more papers by this author
    • fax: (56)-2-7372783


  • Potential conflict of interest: Nothing to report.

Abstract

Recently, we reported that oxidative stress due to 3,3′,5-triiodothyronine (T3)-induced calorigenesis up-regulates the hepatic expression of mediators promoting cell protection. In this study, T3 administration in rats (single dose of 0.1 mg/kg intraperitoneally) induced significant depletion of reduced liver glutathione (GSH), with higher protein oxidation, O2 consumption, and Kupffer cell function (carbon phagocytosis and carbon-induced O2 uptake). These changes occurred within a period of 36 hours of T3 treatment in animals showing normal liver histology and lack of alteration in serum AST and ALT levels. Partial hepatic ischemia-reperfusion (IR) (1 h of ischemia via vascular clamping and 20 h reperfusion) led to 11-fold and 42-fold increases in serum AST and ALT levels, respectively, and significant changes in liver histology, with a 36% decrease in liver GSH content and a 133% increase in that of protein carbonyls. T3 administration in a time window of 48 hours was substantially protective against hepatic IR injury, with a net 60% and 90% reduction in liver GSH depletion and protein oxidation induced by IR, respectively. Liver IR led to decreased DNA binding of nuclear factor-κB (NF-κB) (54%) and signal transducer and activator of transcription 3 (STAT3) (53%) (electromobility shift assay), with 50% diminution in the protein expression of haptoglobin (Western blot), changes that were normalized by T3 preconditioning. Conclusion: T3 administration involving transient oxidative stress in the liver exerts significant protection against IR injury, a novel preconditioning maneuver that is associated with NF-κB and STAT3 activation and acute-phase response. (HEPATOLOGY 2007;45:170–177.)

Ancillary