Inhibition of hepatic outer ring monodeiodination of thyroxine and 3,3',5'-triiodothyronine by sodium salicylate.

Abstract

We have studied, in vitro and in vivo, the effect of sodium salicylate on outer ring monodeiodination of T4 to T3 and of rT3 to 3,3′-diiodothyronine by rat liver. For T4 to T3 conversion studies, 2.5 μm T4 were incubated with 0.22 geq rat liver in 0.15 m phosphate buffer (pH 7.4) for 15 min in the presence of 0–2 mm sodium salicylate, and the amount of T3 produced was quantitated by a specific RIA. Salicylate caused a dose-dependent reduction in T3 generation, with 1.1 mm salicylate causing a 50% reduction. The inhibition of T3 production persisted even in the presence of dithiothreitol (2 mm). Phenacetin (up to 1.9 mm) and acetaminophen (up to 6 mm) caused no detectable effect on T3 production. However, 8-anilino-1-naphthalene sulfonic acid, which, like salicylate, inhibits the binding of iodothyronines to T4-binding globulin, reduced T4 to T3 conversion in a dose-dependent manner; a 50% reduction was caused by about 1.7 mm 8-anilino-1-naphthalene sulfonic acid. A Lineweaver-Burk plot of the data obtaine...