A Mutual Interference between Thyroid Hormones and Antileprous Drugs in the Binding to Human Serum

Abstract

In the precedent paper, the possible relation between thyroid function and the healing mechanism of leprosy was discussed. Now, if the thyroid hormones are subjected to free from human serum under the interference of antileprous drug in vivo, it may intensify the affinity of the hormones to the tissue components of periphery lesions, even though a difference in the peripheral role of the hormones between the leprous lesion and the healthy skin can be considered.
Authors examined the interference of several antileprous drugs in the binding of ¹³¹I-thyroxine (¹³¹I-T₄) to human serum by the use of an in vitro experimental method, radiostereoassay. The drugs employed were di-N-acetyl DDS (DADDS), Ciba 1906, Sulfamethoxypyridazine (all of them are representative drugs adsorbed on albumin, A-type as previously reported), 1314 TH (G-type), and DDS.
The ratio of the bound thyroxine in A per G gradually increased with the concentration of 1314 TH added to the serum, which was supposed to be due to the removal of bound ¹³¹I-T₄ from G to A by the direct interfeeence in the binding of thyroxine to TBG. While, in the cases of the A-type drugs, the rate was contrary diminuted with the concentration of the drugs, or in some case, once diminuted and then increased to form a valley.
When the concentration of thyroxine increased, the valley was apt to remove to the point where the concentration of the drugs was lower than before. This phenomenon can be explained by the following concept that the every binding site of drugs or even hormones is not restricted by a single component, but by an adsorption order on the several components peculiar to a drug or a hormone. Depending upon the concept, the following explanation can be possible. During the diminution of the ratio in A per G, the saturation of TBG by both of thyroxine and one of such drugs may not be reached and the interference by the A-type adsorption of the drug to the slight binding of thyroxine to A is merely emphasized.
While, when TBG is saturated, the non-specific binding of thyroxine to A necessarily increases with the concentration of the drug, thus the valley is formed. In addition, when the concentration of thyroxine or the drug is increased, the mutual interference in TBG may considerably increase, when it is compared with that in A, because the saturation in TBG can be reached more easily than in A and the binding of thyroxine to TBG is well-known to be more stable than to A. Therefore, when the concentration of thyroxine is increased, TBG must be saturated by a lower concentration of the drug, thus the valley removes to the lower concentration of the drug.
Although not so obviously noticed, a similar result in the ratio of prealbumin (PA) per G was detected, as well as in the ratios of A per total and PA per total, in which the total means the radioactivity throughout PA, A, and G.
A diuretic Saltron (4-Chloro-1, 3-disulfonamide) also showed a shallow valley. In the case of DDS, this phenomenon could not be openly apparent, perhaps be due to the comparatively labile binding to human serum, or to the binding type as previously reported.
In conclusion, it can be said that a mutual interference or even a competative relation between thyroxine and several antileperous drugs in the binding to the protein components of human serum is positive, even though it is merely based on an in vitro experimental method.