A FURAN FATTY-ACID AND INDOXYL SULFATE ARE THE PUTATIVE INHIBITORS OF THYROXINE HEPATOCYTE TRANSPORT IN UREMIA
A FURAN FATTY-ACID AND INDOXYL SULFATE ARE THE PUTATIVE INHIBITORS OF THYROXINE HEPATOCYTE TRANSPORT IN UREMIA
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DOI：
10.1210/jc.76.2.318
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发表时间：
1993-02-01
影响因子：
5.8
通讯作者：
HENNEMANN, G
中科院分区：
文献类型：
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作者：
LIM, CF;BERNARD, BF;HENNEMANN, G
我们研究了3-羧基-4-甲基-5-丙基-2-呋喃丙酸（CMPF），硫酸吲哚酚和马尿酸对原代培养大鼠肝细胞碘生成的影响。我们怀疑这些物质是否可以解释肾功能衰竭时血清甲状腺激素参数的改变。在尿毒症患者血清的存在下，大鼠肝细胞从[I-125]T4产生的碘被显著抑制。尿毒症患者血清CMPF、硫酸吲哚酚和马尿酸浓度显著升高。抑制碘化物产生的最小浓度，当表示为抑制剂与BSA的摩尔比时，CMPF为0.13，硫酸吲哚酚为0.53，马尿酸为1.33。该摩尔比低于尿毒症sem中CMPF（0.38）和硫酸吲哚酚（0.63）的相应平均摩尔比，而高于马尿酸（0.85）。当将抑制剂加入正常人血清中时，抑制再现。碘生成的减少不是由于脱碘酶活性的抑制。大鼠肝微粒体对rT 3的脱碘作用不受这些抑制剂的影响，而尿毒症血清的活性炭吸附使肝细胞的碘生成正常化。这种正常化与几乎完全去除CMPF和硫酸吲哚酚相一致，伴随着游离T4部分的减少。尿毒症血清透析只能部分恢复碘的产生。尽管不再检测到硫酸吲哚酚和马尿酸，但血清中仍存在高浓度的CMPF。尿毒症患者透析后血清游离T4分数仍升高，我们的研究表明，CMPF和硫酸吲哚酚浓度正常存在于尿毒症患者的血清中抑制细胞转运和随后的脱碘T4。这些物质可能是尿毒症患者总T3水平低的原因。
We studied the effects of 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), indoxyl sulfate, and hippuric acid on iodide production by rat hepatocytes in primary cultures. We questioned whether these substances could explain the alteration of serum thyroid hormone parameters observed in renal failure. Iodide production from [I-125]T4 by rat hepatocytes was significantly inhibited in the presence of serum from uremic patients. Serum concentrations of CMPF, indoxyl sulfate, and hippuric acid were markedly elevated in uremic patients. The minimum concentration that inhibited iodide production, when expressed as a molar ratio of the inhibitor to BSA, was 0.13 for CMPF, 0.53 for indoxyl sulfate, and 1.33 for hippuric acid. This molar ratio was lower than the corresponding mean molar ratio in uremic sem for CMPF (0.38) and indoxyl sulfate (0.63), while it was higher than that found for hippuric acid (0.85). The inhibition was reproduced when the inhibitors were added to normal human serum. The decreased iodide production was not due to the inhibition of deiodinase activity. The deiodination of rT3 by rat liver microsomes was unaffected by these inhibitors.Charcoal adsorption of uremic serum normalized the iodide production by hepatocytes. This normalization coincided with almost complete removal of CMPF and indoxyl sulfate, with a concomitant reduction of the free T4 fraction. Dialysis of uremic serum only partially restored iodide production. Even though indoxyl sulfate and hippuric acid were no longer detectable, a high concentration of CMPF remained in the serum. The serum free T4 fraction remained elevated in uremic patients after dialysis.Our studies indicate that CMPF and indoxyl sulfate in concentrations normally present in the serum of uremic patients inhibit cellular transport and subsequent deiodination of T4. These substances may account for the ow total T3 level in uremic patients.