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Toxicology. 2013 Dec 6;314(1):22-9. doi: 10.1016/j.tox.2013.08.017. Epub 2013 Sep 3.

Structure-activity relationships of 44 halogenated compounds for iodotyrosine deiodinase-inhibitory activity.

Author information

1
Faculty of Pharmaceutical Sciences, Hiroshima International University, 5-1-1 Hirokoshingai, Kure, Hiroshima 737-0112, Japan. Electronic address: r-shimi@ps.hirokoku-u.ac.jp.

Abstract

The aim of this study was to investigate the possible influence of halogenated compounds on thyroid hormone metabolism via inhibition of iodotyrosine deiodinase (IYD) activity. The structure-activity relationships of 44 halogenated compounds for IYD-inhibitory activity were examined in vitro using microsomes of HEK-293 T cells expressing recombinant human IYD. The compounds examined were 17 polychlorinated biphenyls (PCBs), 15 polybrominated diphenyl ethers (PBDEs), two agrichemicals, five antiparasitics, two pharmaceuticals and three food colorants. Among them, 25 halogenated phenolic compounds inhibited IYD activity at the concentration of 1×10(-4)M or 6×10(-4)M. Rose bengal was the most potent inhibitor, followed by erythrosine B, phloxine B, benzbromarone, 4'-hydroxy-2,2',4-tribromodiphenyl ether, 4-hydroxy-2,3',3,4'-tetrabromodiphenyl ether, 4-hydroxy-2',3,4',5,6'-pentachlorobiphenyl, 4'-hydroxy-2,2',4,5'-tetrabromodiphenyl ether, triclosan, and 4-hydroxy-2,2',3,4',5-pentabromodiphenyl ether. However, among PCBs and PBDEs without a hydroxyl group, including their methoxylated metabolites, none inhibited IYD activity. These results suggest that halogenated compounds may disturb thyroid hormone homeostasis via inhibition of IYD, and that the structural requirements for IYD-inhibitory activity include halogen atom and hydroxyl group substitution on a phenyl ring.

KEYWORDS:

Food colorant; Halogenated phenolic compound; Iodotyrosine deiodinase; Polybrominated diphenyl ether; Polychlorinated biphenyl; Thyroid hormone metabolism

PMID:
24012475
DOI:
10.1016/j.tox.2013.08.017
[Indexed for MEDLINE]
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