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

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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 up-take). 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. T 3 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. Copyright © 2006 by the American Association for the Study of Liver Diseases.

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Fernández, V., Castillo, I., Tapia, G., Romanque, P., Uribe-Echevarría, S., Uribe, M., … Videla, L. A. (2007). Thyroid hormone preconditioning: Protection against ischemia-reperfusion liver injury in the rat. Hepatology, 45(1), 170–177. https://doi.org/10.1002/hep.21476

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