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

Abstract

Recently, we reported that oxidative stress due to 3,3,5-triiodothyronine (T 3 )-induced calorigenesis up-regulates the hepatic expression of mediators promoting cell protection. In this study, T 3 administration in rats (single dose of 0.1 mg/kg intraperitoneally) induced significant depletion of reduced liver glutathione (GSH), with higher protein oxidation, O 2 consumption, and Kupffer cell function (carbon phagocytosis and carbon-induced O 2 uptake). These changes occurred within a period of 36 hours of T 3 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-B (NF-B) (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 T 3 preconditioning. Conclusion: T 3 administration involving transient oxidative stress in the liver exerts significant protection against IR injury, a novel preconditioning maneuver that is associated with NF-B and STAT3 activation and acute-phase response. (HEPATOLOGY 2007;45:170-177.)

Hormetic responses of thyroid hormone calorigenesis in the liver: Association with oxidative stress

“…The hormetic responses involved in thyroid hormone-induced liver preconditioning against IR injury (78) are also observed in the heart (88,89), with a pattern of protection closely resembling that of ischemic preconditioning (90), and constitute a preconditioning strategy that have clinical potential. This is an important issue considering that pharmacological and other liver preconditioning maneuvers have not been transferred to clinical application, with the exception of ischemic preconditioning (91).…”

Thyroid hormone metabolism in innate immune cells

“…This ultimately increases liver iNOS expression and activity 232:2 together with other markers of oxidative stress including decreased liver glutathione content (an important antioxidant) and higher protein oxidation (Fig. 2B) (Tapia et al 1997, 2006, Valencia et al 2004, Fernandez et al 2005, 2007a. Conversely, another study found that T 3 inhibited STAT3 signalling in macrophages after LPS or IL-6 stimulation and had no effect on TNFα induction and NFκB activation in vitro (Contreras-Jurado et al 2016).…”

“…Several studies by the same group have analysed the effect of TH administration on rat liver and the role of Kupffer cells in this process. T 3 administration induces oxidative stress in the liver (Tapia et al 1997, 2006, 2010, Valencia et al 2004, Fernandez et al 2005, 2007a,b, 2008. This is thought to be mediated via Kupffer cells, which demonstrate hyperplasia, increased phagocytic capacity, increased ROS generation and tumour necrosis factor α (TNFα) production in response to T 3 administration in vivo (Fig.…”

“…Hepatic ischaemic reperfusion injury in rats results in severe liver damage (Fernandez et al 2007a, 2008, Tapia et al 2010. These effects were prevented and even reversed by preconditioning with a single dose of T 3 (Fernandez et al 2007a, 2008, Tapia et al 2010.…”

Changes in the hemodynamic and thyroid functions of rats treated by opium

“…However, prolonged stress may cause an elevation in cortisol concentrations as the adrenal glands respond to the stress. The high cortisol levels inhibit the conversion of T4 to T3 [41]. On the other hand, loss of thyroid-binding protein in urine under the effects of oxidative stress could be another cause of decrease in serum T3 and T4 levels.…”