Triiodothyronine attenuates hepatic ischemia/reperfusion injury in a partial hepatectomy model through inhibition of proinflammatory cytokines, transcription factors, and adhesion molecules.
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.


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.


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.


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.
Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Ahmed
A
Taki-Eldin
Lin
L
Zhou
Hai-Yang
HY
Xie
Kang-Jie
KJ
Chen
Da
D
Yu
Yong
Y
He
Shu-Sen
SS
Zheng
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors*; D049109:Cell Proliferation; D016207:Cytokines / Q000037:antagonists & inhibitors*; D006498:Hepatectomy; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors*; D014284:Triiodothyronine / Q000494:pharmacology* / Q000627:therapeutic use
D015815:Cell Adhesion Molecules; D016207:Cytokines; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014284:Triiodothyronine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase