Effect of Erythrosine (2′,4′,5′,7′-Tetraiodofluorescein) on the Metabolism of Thyroxine in Rat Liver*

Abstract

Studies were performed to determine the effects of erythrosine (2′,4′,5′,7′-tetraiodofluorescein; FD&C red no. 3), a widely used coloring agent for foods and pharmaceutical preparations, on the metabolism of ¹²⁵I-labeled T₄ and T₃ by rat liver homogenates. When added in vitro to either buffer or homogenates, erythrosine produced a prompt and marked, nonenzymatic deiodination of [¹²⁵I]T₄. In buffer, this effect of erythrosine was shown to be decreased by the exclusion of light or the addition of serotonin. In view of these findings, the remaining studies examined the effects of administering erythrosine to rats in vivo on the metabolism of [¹²⁵I]T₄ and [¹²⁵I]T₃ by homogenates of their livers in vitro. Over a wide range of doses (2.5–250 mg/ kg BW./day), erythrosine induced a dose-dependent inhibition of the deiodination of [¹²⁵I]T₄ and the generation of [¹²⁵I]T₃ therefrom, effects that were uninfluenced by the exclusion of light from the incubation system. At higher doses of erythrosine, the proportionate reduction of the deiodination of [¹²⁵I]T₄ exceeded that of the generation of [¹²⁵I]T₃, indicating that the pathways of T₄ metabolism other than that leading to T₃ formation were also inhibited. Evidence was adduced that erythrosine may inhibit the 5-monodeiodination of T₄ that generates rT₃, especially since the administration of erythrosine also led to the inhibition of the 5-monodeiodination of T₃ that leads to the generation of 3,3′-diiodothyronine. Fluorescein, the noniodinated analog of erythrosine, did not induce a photoactivated deiodination of [¹²⁵I]T_4, in buffer in vitro, and had no effect on the in vitro hepatic metabolism of T₄ when administered in vivo The foregoing findings indicate that erythrosine, like other iodinated aromatic dyes, is capable of inhibiting the 5′-monodeiodination of T₄ and very likely inhibits other pathways of hepatic T₄ metabolism as well. The possibility that erythrosine produces similar effects in man in the doses normally ingested is discussed, but is considered unlikely.