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

AbstractUNLABELLED:
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-kappaB (NF-kappaB) (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-kappaB and STAT3 activation and acute-phase response.
AuthorsVirginia Fernández, Iván Castillo, Gladys Tapia, Pamela Romanque, Sebastián Uribe-Echevarría, Mario Uribe, Denise Cartier-Ugarte, Gonzalo Santander, María T Vial, Luis A Videla
JournalHepatology (Baltimore, Md.) (Hepatology) Vol. 45 Issue 1 Pg. 170-7 (Jan 2007) ISSN: 0270-9139 [Print] United States
PMID17187421 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • NF-kappa B
  • STAT3 Transcription Factor
  • Triiodothyronine
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Glutathione
Topics
  • Acute-Phase Reaction (physiopathology)
  • Alanine Transaminase (blood, genetics)
  • Animals
  • Aspartate Aminotransferases (blood, genetics)
  • Gene Expression Regulation (drug effects)
  • Glutathione (genetics, metabolism)
  • Ischemic Preconditioning (methods)
  • Liver (metabolism, physiopathology)
  • Male
  • NF-kappa B (genetics, metabolism)
  • Oxidative Stress (drug effects)
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury (metabolism, physiopathology, prevention & control)
  • STAT3 Transcription Factor (genetics, metabolism)
  • Signal Transduction (physiology)
  • Thyroid Gland (blood supply, drug effects, metabolism, physiopathology)
  • Triiodothyronine (pharmacology)

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