Tri-iodothyronine as a stimulator of liver regeneration after partial and subtotal hepatectomy.
BACKGROUND
Tri-iodothyronine (T3) has been shown to be a hepatic mitogen. We investigated whether exogenous application of T3 improves liver regeneration after 70% partial hepatectomy (PH) and confers a survival advantage after 90% subtotal hepatectomy (SH) in rats and whether this is associated with the stimulation of angiogenesis.


METHODS
Rats were subjected to PH or SH 10 days after injection of a single dose of T3. Liver body weight ratio (LBR), hepatic proliferation (Ki-67), biochemical markers as well as vascular endothelial growth factor (VEGF) expression were assessed by immunohistochemistry. Gene expression of pathogenic relevant genes was determined by customized cDNA arrays and quantitative RT-PCR.


RESULTS
T3-treated rats showed an increased LBR and Ki-67 index after PH and SH, which reached statistical significance compared to placebo-treated rats (p < 0.05). On the transcriptional level, T3-treated rats had an increased expression of VEGF as demonstrated by immunohistochemistry, which was associated with a higher expression of its receptor Flt-1.


CONCLUSIONS
Exogenous administration of T3 ameliorates liver regeneration after 70% PH and 90% SH, possibly due to stimulation of angiogenesis. Therefore, its clinical use might be of interest due to its excellent general practicability.
Bockhorn
M
M
Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany. maximilian.bockhorn@uk-essen.de
Frilling
A
A
Benko
T
T
Best
J
J
Sheu
S-Y
SY
Trippler
M
M
Schlaak
J F
JF
Broelsch
C E
CE
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002455:Cell Division / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D005969:Glutamate Dehydrogenase / Q000097:blood; D006498:Hepatectomy; D019394:Ki-67 Antigen / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000601:surgery; D008115:Liver Regeneration / Q000187:drug effects* / Q000235:genetics; D016031:Liver Transplantation; D019520:Living Donors; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate; D014284:Triiodothyronine / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D019394:Ki-67 Antigen; D042461:Vascular Endothelial Growth Factor A; D014284:Triiodothyronine; D005969:Glutamate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase