Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5859307 | Toxicology | 2013 | 8 Pages |
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 1Â ÃÂ 10â4Â M or 6Â ÃÂ 10â4Â M. Rose bengal was the most potent inhibitor, followed by erythrosine B, phloxine B, benzbromarone, 4â²-hydroxy-2,2â²,4-tribromodiphenyl ether, 4-hydroxy-2,3â²,3,4â²-tetrabromodiphenyl ether, 4-hydroxy-2â²,3,4â²,5,6â²-pentachlorobiphenyl, 4â²-hydroxy-2,2â²,4,5â²-tetrabromodiphenyl ether, triclosan, and 4-hydroxy-2,2â²,3,4â²,5-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.
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Authors
Ryo Shimizu, Masafumi Yamaguchi, Naoto Uramaru, Hiroaki Kuroki, Shigeru Ohta, Shigeyuki Kitamura, Kazumi Sugihara,