Wang R, Nelson J C, Wilcox R B
Department of Biochemistry, School of Medicine, Loma Linda University, California 92354, USA.
Thyroid. 1999 Apr;9(4):359-64. doi: 10.1089/thy.1999.9.359.
Salsalate and its metabolite salicylate are inhibitors of thyroid hormone binding to serum transport proteins and reduce serum total thyroxine (T4) and triiodothyronine (T3) in vivo. The present study is the first to examine and compare salsalate and salicylate binding to human thyroxine-binding globulin (TBG), transthyretin (TTR), albumin (ALB), and whole human serum, and displacement by salsalate and salicylate of T4 from isolated TBG, TTR, ALB. Salsalate and salicylate binding were studied by ultrafiltration at salsalate concentrations of 0.24-1.16 mM (62-300 microg/mL) and salicylate concentrations of 0.0375-2.25 mM (6.0-360 microg/mL). T4 displacement by salsalate and salicylate from TBG, TTR, and ALB was studied by equilibrium dialysis at salsalate concentrations of 0 to 1.52 mM (0-393 microg/mL) and salicylate concentrations of 0 to 60 mM (0-9600 microg/mL). In normal human serum, 95% of salsalate and 76% of salicylate were protein-bound. In the presence of isolated ALB, 89% of salsalate and 64% of salicylate were ALB-bound. Both salsalate and salicylate inhibited T4 binding to all 3 major T4 binding proteins. Both displaced proportionately more T4 from TBG compared with TTR and ALB. The principal site to which both salsalate and salicylate in serum is bound (ALB) is different from the principal site from which they displace T4 (TBG). Salsalate potency in displacing T4 from TBG and ALB was approximately 100-fold greater than salicylate potency.
双水杨酯及其代谢产物水杨酸是甲状腺激素与血清转运蛋白结合的抑制剂，可在体内降低血清总甲状腺素（T4）和三碘甲状腺原氨酸（T3）水平。本研究首次检测并比较了双水杨酯和水杨酸与人甲状腺素结合球蛋白（TBG）、转甲状腺素蛋白（TTR）、白蛋白（ALB）以及全人血清的结合情况，以及双水杨酯和水杨酸从分离的TBG、TTR、ALB中置换T4的能力。通过超滤研究双水杨酯和水杨酸的结合情况，双水杨酯浓度为0.24 - 1.16 mM（62 - 300 μg/mL），水杨酸浓度为0.0375 - 2.25 mM（6.0 - 360 μg/mL）。通过平衡透析研究双水杨酯和水杨酸从TBG、TTR和ALB中置换T4的能力，双水杨酯浓度为0至1.52 mM（0 - 393 μg/mL），水杨酸浓度为0至60 mM（0 - 9600 μg/mL）。在正常人血清中，95%的双水杨酯和76%的水杨酸与蛋白结合。在存在分离的ALB时，89%的双水杨酯和64%的水杨酸与ALB结合。双水杨酯和水杨酸均抑制T4与所有3种主要T4结合蛋白的结合。与TTR和ALB相比，二者从TBG中置换出的T4比例更大。血清中双水杨酯和水杨酸结合的主要位点（ALB）与它们置换T4的主要位点（TBG）不同。双水杨酯从TBG和ALB中置换T4的效力比水杨酸的效力大约高100倍。
