Amiodarone inhibits T4 to T3 conversion and alpha-glycerophosphate dehydrogenase and malic enzyme levels in rat liver.
Amiodarone has been found to decrease serum T3 by blocking peripheral T4 5'-deiodinase. This reduction in T3 levels may contribute to the effectiveness of this drug in moderating cardiac arrhythmias. To further characterize the effect of amiodarone on thyroid hormone metabolism and biological action, male Sprague-Dawley rats were thyroidectomized and then fed 500 ug T4 or 50 ug T3 and 500 mg amiodarone/kg of powdered diet for 6 to 8 weeks. Hepatic and cardiac levels of T4, T3, alpha-glycerophosphate dehydrogenase (GPD) and malic enzyme (ME) were used as indicators of thyroid hormone availability and action at the cellular level. Conversion of T4 to T3 was measured in liver homogenates. Serum TSH, T4 and T3 were also measured. Amiodarone reduced hepatic GPD and ME in thyroidectomized rats receiving dietary T4. Liver T4 levels were significantly increased by amiodarone and the T3/T4 ratio was reduced (P less than .05). Amiodarone inhibited hepatic T4 to T3 conversion and decreased serum T3. The decreased T3 action at the cellular level, indicated by the reduction in hepatic GPD and ME, is not due to pharmacologic effects of amiodarone since these enzyme levels were not affected by amiodarone in thyroidectomized rats replaced with T3.
Pekary
A E
AE
Hershman
J M
JM
Reed
A W
AW
Kannon
R
R
Wang
Y S
YS
D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D001711:Biotransformation; D002118:Calcium / Q000097:blood; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008274:Magnesium / Q000097:blood; D008291:Malate Dehydrogenase / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013965:Thyroidectomy; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism*
D001572:Benzofurans; D014284:Triiodothyronine; D013972:Thyrotropin; D005993:Glycerolphosphate Dehydrogenase; D008291:Malate Dehydrogenase; D008274:Magnesium; D000638:Amiodarone; D013974:Thyroxine; D002118:Calcium