1. An assay for screening xenobiotics for inhibition of rat thyroid gland peroxidase activity
- Author
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R.J. Price, Brian G. Lake, Richard A. Currie, Larry G. Higgins, Lynsey R. Chatham, and Rachel Burch
- Subjects
endocrine system ,medicine.medical_specialty ,endocrine system diseases ,Health, Toxicology and Mutagenesis ,Thyroid Peroxidase Inhibitors ,Thyroid Gland ,Toxicology ,Iodide Peroxidase ,030226 pharmacology & pharmacy ,Biochemistry ,Xenobiotics ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Thyroid peroxidase ,Internal medicine ,medicine ,Animals ,Enzyme Inhibitors ,Pharmacology ,biology ,Chemistry ,Thyroid ,General Medicine ,Rats ,medicine.anatomical_structure ,Endocrinology ,030220 oncology & carcinogenesis ,biology.protein ,Thyroid hormone synthesis ,Biological Assay ,Xenobiotic ,Rat Thyroid Gland ,Peroxidase - Abstract
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 IC
- Published
- 2019
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