Journal
XENOBIOTICA
Volume 50, Issue 3, Pages 318-322Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/00498254.2019.1629044
Keywords
Thyroid gland; thyroid peroxidase; thyroid peroxidase inhibitors; rat thyroid gland microsomes; iodination of L-tyrosine; mass spectrometric analysis
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Funding
- LFR Molecular Sciences
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1. A number of chemicals have been shown to produce disruption of the thyroid gland, resulting in reduced thyroid hormone synthesis, by a mechanism involving inhibition of thyroid peroxidase (TPO) activity (EC 1.11.1.8). 2. An assay was developed for rat thyroid gland microsomal TPO activity, employing L-tyrosine as the physiological substrate, with analysis of the formation of the 3-iodo-L-tyrosine (3MIT) metabolite by ultra-performance liquid chromatography-mass spectrometry-mass spectrometry. 3. Formation of 3MIT was linear with respect to both rat thyroid gland microsomal protein concentration and incubation time, whereas only small quantities of 3,5-diodo-L-tyrosine were formed. 4. Studies were performed with nine known TPO inhibitors. The most potent inhibitors were 3-amino-1,2,4-triazole, ethylene thiourea, methimazole and 6-propyl-2-thiouracil which had IC50 values (i.e. concentration to produce a 50% inhibition of enzyme activity) of 0.059, 0.791, 1.07 and 1.96 mu M, respectively, whereas the least potent inhibitor was sodium perchlorate which had an IC50 value of 13,800 mu M. 5. For five inhibitors, where literature data were available, the observed IC50 values obtained in this study employing rat thyroid gland microsomes and L-tyrosine as substrate were similar to those previously reported using the spectrophotometric guaiacol oxidation assay.
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