Inhibition of thyroid peroxidase by dietary flavonoids
Divi, RL; Doerge, DR
HERO ID
1412882
Reference Type
Journal Article
Year
1996
Language
English
PMID
| HERO ID | 1412882 |
|---|---|
| In Press | No |
| Year | 1996 |
| Title | Inhibition of thyroid peroxidase by dietary flavonoids |
| Authors | Divi, RL; Doerge, DR |
| Journal | Chemical Research in Toxicology |
| Volume | 9 |
| Issue | 1 |
| Page Numbers | 16-23 |
| Abstract | Flavonoids are widely distributed in plant-derived foods and possess a variety of biological activities including antithyroid effects in experimental animals and humans. A structure-activity study of 13 commonly consumed flavonoids was conducted to evaluate inhibition of thyroid peroxidase (TPO), the enzyme that catalyzes thyroid hormone biosynthesis. Most flavonoids tested were potent inhibitors of TPO, with IC50 values ranging from 0.6 to 41 microM. Inhibition by the more potent compounds, fisetin, kaempferol, naringenin, and quercetin, which contain a resorcinol moiety, was consistent with mechanism-based inactivation of TPO as previously observed for resorcinol and derivatives. Other flavonoids inhibited TPO by different mechanisms, such as myricetin and naringin, showed noncompetitive inhibition of tyrosine iodination with respect to iodine ion and linear mixed-type inhibition with respect to hydrogen peroxide. In contrast, biochanin A was found to be an alternate substrate for iodination. The major product, 6,8-diiodo-biochanin A, was characterized by electrospray mass spectrometry and 1H-NMR. These inhibitory mechanisms for flavonoids are consistent with the antithyroid effects observed in experimental animals and, further, predict differences in hazards for antithyroid effects in humans consuming dietary flavonoids. In vivo, suicide substrate inhibition, which could be reversed only by de novo protein synthesis, would be long-lasting. However, the effects of reversible binding inhibitors and alternate substrates would be temporary due to attenuation by metabolism and excretion. The central role of hormonal regulation in growth and proliferation of thyroid tissue suggests that chronic consumption of flavonoids, especially suicide substrates, could play a role in the etiology of thyroid cancer. |
| Doi | 10.1021/tx950076m |
| Pmid | 8924586 |
| Wosid | WOS:A1996TU00200005 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Journal: ISSN: |
| Is Public | Yes |
| Language Text | English |