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Triiodothyronine attenuates hepatic ischemia/reperfusion injury in a partial hepatectomy model through inhibition of proinflammatory cytokines, transcription factors, and adhesion molecules.
- Source :
-
The Journal of surgical research [J Surg Res] 2012 Dec; Vol. 178 (2), pp. 646-56. Date of Electronic Publication: 2012 Jun 15. - Publication Year :
- 2012
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Abstract
- Background: Hepatic ischemia/reperfusion (I/R) injury during liver surgery and transplantation is the main cause of postoperative liver failure and primary graft nonfunction, with subsequent rise in mortality in these patients. Triiodothyronine (T3) is a known hepatic mitogen. In this study we questioned whether exogenous administration of T3 protects against warm hepatic I/R injury.<br />Materials and Methods: T3 or vehicle was administered to male Sprague-Dawley rats (single dose of 0.5 mg/kg intraperitoneally) 48 h before hepatic ischemia, then the rats were subjected to 60 min of partial hepatic I/R followed by 50% hepatectomy. Serum transaminases, histopathologic changes, apoptosis, malondialdehyde, and myeloperoxidase were evaluated. The expression of proinflammatory cytokines (TNF-α, IL-1β, and IL-6), transcription factors (NF-кB and AP-1), and adhesion molecules (ICAM-1, VCAM-1) was also investigated.<br />Results: Rats pretreated with T3 showed significant reduction of their postischemic hepatic injury (serum transaminases, liver necrosis, and apoptosis). Also, production of reactive oxygen species and neutrophil infiltration were markedly depressed by T3 administration. This was associated with downregulation of proinflammatory cytokines, transcription factors, and adhesion molecules.<br />Conclusions: This study illustrated that T3 protects against hepatic I/R injury, an effect that is mediated through inhibition of proinflammatory cytokines, transcription factors, and adhesion molecules. Pretreatment with T3 may represent a promising pharmacologic strategy for protection against hepatic I/R injury.<br /> (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Subjects :
- Alanine Transaminase blood
Animals
Apoptosis drug effects
Aspartate Aminotransferases blood
Cell Proliferation
Lipid Peroxidation drug effects
Liver pathology
Male
Rats
Rats, Sprague-Dawley
Triiodothyronine therapeutic use
Cell Adhesion Molecules antagonists & inhibitors
Cytokines antagonists & inhibitors
Hepatectomy
Liver blood supply
NF-kappa B antagonists & inhibitors
Reperfusion Injury prevention & control
Transcription Factor AP-1 antagonists & inhibitors
Triiodothyronine pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1095-8673
- Volume :
- 178
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Journal of surgical research
- Publication Type :
- Academic Journal
- Accession number :
- 22727940
- Full Text :
- https://doi.org/10.1016/j.jss.2012.05.069