Amiodarone Inhibits T₄ to T₃ Conversion and α-Glycerophosphate Dehydrogenase and Malic Enzyme Levels in Rat Liver

Summary

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, α-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 < .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.

Key-Words

Amiodarone - α-Glycerophosphate Dehydrogenase - malic Enzyme - 5′-Monodeiodinase - Triiodothyronine