The effects of thyroid hormone modulation on rat liver injury associated with ischemia-reperfusion and cold storage.
We investigated the effects of thyroid hormone modulation on liver injury associated with ischemia-reperfusion (I-R) and cold storage in rats. First, euthyroid and thyroxine (T4)-pretreated rats were exposed in vivo to 20-min global liver ischemia, then 30-min reperfusion. Liver injury was assessed by measuring serum alanine aminotransferase (ALT) levels. Liver concentrations of adenine nucleotides, reduced glutathione (GSH), and oxidized glutathione were evaluated. Second, rats were given the antithyroid drug propylthiouracil (PTU). Livers stored at 0-1 degrees C in Euro-Collins' solution for 20 h were reperfused at 37 degrees C for 15 min. Lactate dehydrogenase (LDH) in the effluent perfusate and bile flow were evaluated during reperfusion. Serum ALT levels increased after ischemia and I-R. ALT increased significantly more in T4-pretreated than in euthyroid rats after ischemia and I-R. Preischemic levels of adenosine triphosphate (ATP) were significantly lower in livers from T4-pretreated than in euthyroid rats (6.22 +/- 0.7 and 11 +/- 0.9 nmol/mg protein, respectively; P < 0.05). After ischemia, liver ATP was similarly reduced in T4-pretreated and euthyroid rats. After reperfusion, ATP partially recovered in euthyroid rats but remained low in T4-pretreated rats (6.7 +/- 1.0 and 1.91 +/- 0.7 nmol/mg protein, respectively; P < 0.05). Preischemic levels of liver GSH decreased to 44% in T4-pretreated rats. After ischemia, GSH decreased similarly in euthyroid and T4-pretreated rats. GSH recovered promptly after reperfusion in euthyroid rats but remained low in T4-pretreated rats (13.9 +/- 3.3 and 3.9 +/- 0.9 nmol/mg protein, respectively; P < 0.02). During reperfusion after cold storage, LDH in effluent perfusate was significantly lower and bile flow higher in livers from PTU-pretreated rats than from euthyroid rats. The histopathological changes observed after I-R and cold storage confirmed the biochemical findings. Our results suggest that T4 administration exacerbates pretransplant liver damage by increasing liver susceptibility to I-R, whereas PTU administration reduces the liver injury associated with cold storage.


CONCLUSIONS
We studied the effects of thyroid hormone modulation on liver injury associated with ischemia-reperfusion and cold storage in rats. Thyroxine administration increased susceptibility to ischemia-reperfusion injury, whereas the antithyroid agent propylthiouracil reduced the deleterious effects associated with cold storage.
Imberti
R
R
Servizio di Anestesia e Rianimazione II, IRCCS Policlinico S. Matteo and University of Pavia, Italy.
Vairetti
M
M
Gualea
M R
MR
Feletti
F
F
Poma
G
G
Richelmi
P
P
Preseglio
I
I
Bellomo
G
G
D000227:Adenine Nucleotides / Q000032:analysis; D000255:Adenosine Triphosphate / Q000032:analysis; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology; D001646:Bile / Q000378:metabolism; D015925:Cryopreservation; D004198:Disease Susceptibility; D005978:Glutathione / Q000032:analysis; D006982:Hypertonic Solutions / Q000627:therapeutic use; D007511:Ischemia / Q000503:physiopathology*; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016031:Liver Transplantation; D008297:Male; D019188:Organ Preservation Solutions / Q000627:therapeutic use; D011441:Propylthiouracil / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D013963:Thyroid Hormones / Q000008:administration & dosage / Q000627:therapeutic use*; D013974:Thyroxine / Q000008:administration & dosage / Q000627:therapeutic use
D000227:Adenine Nucleotides; D013956:Antithyroid Agents; C037096:Euro-Collins' solution; D006982:Hypertonic Solutions; D019188:Organ Preservation Solutions; D013963:Thyroid Hormones; D011441:Propylthiouracil; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D000410:Alanine Transaminase; D005978:Glutathione; D013974:Thyroxine