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 inj ury associated with ischemia-reperfusion (I-R) and cold storage in rat s. First, euthyroid and thyroxine (T-4)-pretreated rats were exposed i n 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 glutathi one (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 d egrees C for 15 min. Lactate dehydrogenase (LDH) in the effluent perfu sate and bile flow were evaluated during reperfusion. Serum ALT levels increased after ischemia and I-R. ALT increased significantly more in T-4-pretreated than in euthyroid rats after ischemia and I-R. Preisch emic levels of adenosine triphosphate (ATP) were significantly lower i n livers from T-4-pretreated than in euthyroid rats (6.22 +/- 0.7 and 11 +/- 0.9 nmol/mg protein, respectively; P < 0.05). After ischemia, L iver Am was similarly reduced in T-4-pretreated and euthyroid rats. Af ter reperfusion, Am partially recovered in euthyroid rats but remained low in T-4-pretreated rats (6.7 +/- 1.0 and 1.91 +/- 0.7 nmol/mg prot ein, respectively; P < 0.05). Preischemic levels of liver GSH decrease d to 44% in T-4-pretreated rats. After ischemia, GSH decreased similar ly in euthyroid and T-4-pretreated rats. GSH recovered promptly after reperfusion in euthyroid rats but remained low in T-4-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-pretreate d rats than from euthyroid rats. The histoyathological changes observe d after I-R and cold storage confirmed the biochemical findings. Our r esults suggest that T-4 administration exacerbates pretransplant liver damage by increasing liver susceptibility to I-R, whereas PTU adminis tration reduces the liver injury associated with cold storage. Implica tions: We studied the effects of thyroid hormone modulation on liver i njury associated with ischemia-reperfusion and cold storage in rats. T hyroxine administration increased susceptibility to ischemia-reperfusi on injury, whereas the antithyroid agent propylthiouracil reduced the deleterious effects associated with cold storage.