Abstract | UNLABELLED: 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.
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Authors | Virginia Fernández, Iván Castillo, Gladys Tapia, Pamela Romanque, Sebastián Uribe-Echevarría, Mario Uribe, Denise Cartier-Ugarte, Gonzalo Santander, María T Vial, Luis A Videla |
Journal | Hepatology (Baltimore, Md.)
(Hepatology)
Vol. 45
Issue 1
Pg. 170-7
(Jan 2007)
ISSN: 0270-9139 [Print] United States |
PMID | 17187421
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- NF-kappa B
- STAT3 Transcription Factor
- Triiodothyronine
- Aspartate Aminotransferases
- Alanine Transaminase
- Glutathione
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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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