Anti-thyroid isoflavones from soybean - Isolation, characterization, and mechanisms of action

被引:190
作者
Divi, RL [1 ]
Chang, HC [1 ]
Doerge, DR [1 ]
机构
[1] NATL CTR TOXICOL RES,JEFFERSON,AR 72079
关键词
thyroid peroxidase; soybean; isoflavonoid; inhibitor; goitrogen; mechanism;
D O I
10.1016/S0006-2952(97)00301-8
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The soybean has been implicated in diet-induced goiter by many studies. The extensive consumption of soy products in infant formulas and in Vegetarian diets makes it essential to define the goitrogenic potential. In this report, it was observed chat an acidic methanolic extract of soybeans contains compounds that inhibit thyroid peroxidase- (TPO) catalyzed reactions essential to thyroid hormone synthesis. Analysis of the soybean extract using HPLC, UV-VIS spectrophotometry, and LC-MS led to identification of the isoflavones genistein and daidzein as major components by direct comparison with authentic standard reference isoflavones. HPLC fractionation and enzymatic assay of the soybean extract showed that the components responsible for inhibition of TPO-catalyzed reactions coeluted with daidzein and genistein. In the presence of iodide ion, genistein and daidzein blocked TPO-catalyzed tyrosine iodination by acting as alternate substrates, yielding mono-, di-, and triiodoisoflavones. Genistein also inhibited thyroxine synthesis using iodinated casein or human goiter thyroglobulin as substrates for the coupling reaction. Incubation of either isoflavone with TPO in the presence of H2O2 caused irreversible inactivation of the enzyme; however, the presence of iodide ion in the incubations completely abolished the inactivation. The IC50 values for inhibition of TPO-catalyzed reactions by genistein and daidzein were ca. 1-10 mu M, concentrations that approach the total isoflavone levels (ca. 1 mu M) previously measured in plasma from humans consuming soy products. Because inhibition of thyroid hormone synthesis can induce goiter and thyroid neoplasia in rodents, delineation of anti-thyroid mechanisms for soy isoflavones may be important for extrapolating goitrogenic hazards identified in chronic rodent bioassays to humans consuming soy products. (C) 1997 Elsevier Science Inc.
引用
收藏
页码:1087 / 1096
页数:10
相关论文
共 36 条
[1]  
ANDERSON RL, 1995, J NUTR, V125, pS581, DOI 10.1093/jn/125.3_Suppl.581S
[2]   THE USE OF THERMOSPRAY LIQUID-CHROMATOGRAPHY TANDEM MASS-SPECTROMETRY FOR THE CLASS IDENTIFICATION AND STRUCTURAL VERIFICATION OF PHYTOESTROGENS IN SOY PROTEIN PREPARATIONS [J].
BARBUCH, RJ ;
COUTANT, JE ;
WELSH, MB ;
SETCHELL, KDR .
BIOMEDICAL AND ENVIRONMENTAL MASS SPECTROMETRY, 1989, 18 (11) :973-977
[3]  
BARNES S, 1995, J CELL BIOCH S, V22, P181
[4]  
BLOCK JR, 1961, ARCH BIOCHEM BIOPHYS, V93, P15
[5]  
Chopra Inder J., 1996, P111
[6]   Analysis of plasma isoflavones by reversed-phase HPLC-multiple reaction ion monitoring-mass spectrometry [J].
Coward, L ;
Kirk, M ;
Albin, N ;
Barnes, S .
CLINICA CHIMICA ACTA, 1996, 247 (1-2) :121-142
[7]   Inhibition of thyroid peroxidase by dietary flavonoids [J].
Divi, RL ;
Doerge, DR .
CHEMICAL RESEARCH IN TOXICOLOGY, 1996, 9 (01) :16-23
[8]   MECHANISM-BASED INACTIVATION OF LACTOPEROXIDASE AND THYROID PEROXIDASE BY RESORCINOL DERIVATIVES [J].
DIVI, RL ;
DOERGE, DR .
BIOCHEMISTRY, 1994, 33 (32) :9668-9674
[9]  
Doerge DR, 1995, J MASS SPECTROM, pS136
[10]   Mechanism for the anti-thyroid action of minocycline [J].
Doerge, DR ;
Divi, RL ;
Deck, J ;
Taurog, A .
CHEMICAL RESEARCH IN TOXICOLOGY, 1997, 10 (01) :49-58