Evaluation of Oleic Acid, Arachidonic Acid, and Various Drugs as Competitors for Serum Binding of Thyroxine
Numerous drugs can displace thyroid hormones from plasma protein binding (1,2), and it has been suggested that substances of endogenous origin can also inhibit binding, particularly in severe non-thyroidal illness (35). The potency of a competitor is influenced by at least three factors: total circulating concentration, free fraction in undiluted serum, and relative affinity for T4 binding sites. From these three factors, a prediction of inhibitory potency can be made. This prediction can be tested by measuring the effect of circulating concentrations of potential inhibitors on 125I T4 binding in undiluted serum at 37°C. In this study, we examine these predictions for furosemide, various nonsteroidal anti-inflammatory drugs, and free fatty acids (FFA), which have been assessed because they appear to be promising candidates as thyroid hormone-binding inhibitors (THBI) (3). Recent studies suggest that oleic acid may contribute more importantly to THBI of non-thyroidal illness than other FFA (4). In these studies (3–5), binding was assessed using diluted serum in a competitive ligand binding assay. We have examined the effect of serum dilution on the apparent inhibitory potency of added FFA in order to evaluate effects seen in such assays.
KeywordsFree Fatty Acid Oleic Acid Free Fraction Mefenamic Acid Equilibrium Dialysis
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