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Endocrinol Metab (Seoul). 2016 Mar;31(1):174-84. doi: 10.3803/EnM.2016.31.1.174.

Propylthiouracil, Perchlorate, and Thyroid-Stimulating Hormone Modulate High Concentrations of Iodide Instigated Mitochondrial Superoxide Production in the Thyroids of Metallothionein I/II Knockout Mice.

Endocrinology and metabolism (Seoul, Korea)

Qi Duan, Tingting Wang, Na Zhang, Vern Perera, Xue Liang, Iruni Roshanie Abeysekera, Xiaomei Yao

Affiliations

  1. Department of Pathophysiology, School of Basic Medical Science, Tianjin Medical University, Tianjin, China.
  2. Department of Pathophysiology, School of Basic Medical Science, Tianjin Medical University, Tianjin, China. [email protected].

PMID: 26754589 PMCID: PMC4803556 DOI: 10.3803/EnM.2016.31.1.174

Abstract

BACKGROUND: Increased oxidative stress has been suggested as one of the underlying mechanisms in iodide excess-induced thyroid disease. Metallothioneins (MTs) are regarded as scavengers of reactive oxygen species (ROS) in oxidative stress. Our aim is to investigate the effects of propylthiouracil (PTU), a thyroid peroxidase inhibitor, perchlorate (KClO₄), a competitive inhibitor of iodide transport, and thyroid stimulating hormone (TSH) on mitochondrial superoxide production instigated by high concentrations of iodide in the thyroids of MT-I/II knockout (MT-I/II KO) mice.

METHODS: Eight-week-old 129S7/SvEvBrd-Mt1(tm1Bri) Mt2(tm1Bri)/J (MT-I/II KO) mice and background-matched wild type (WT) mice were used.

RESULTS: By using a mitochondrial superoxide indicator (MitoSOX Red), lactate dehydrogenase (LDH) release, and methyl thiazolyl tetrazolium (MTT) assay, we demonstrated that the decreased relative viability and increased LDH release and mitochondrial superoxide production induced by potassium iodide (100 μM) can be relieved by 300 μM PTU, 30 μM KClO₄, or 10 U/L TSH in the thyroid cell suspensions of both MT-I/II KO and WT mice (P<0.05). Compared to the WT mice, a significant decrease in the relative viability along with a significant increase in LDH release and mitochondrial superoxide production were detected in MT-I/II KO mice(P<0.05).

CONCLUSION: We concluded that PTU, KClO₄, or TSH relieved the mitochondrial oxidative stress induced by high concentrations of iodide in the thyroids of both MT-I/II KO and WT mice. MT-I/II showed antioxidant effects against high concentrations of iodide-induced mitochondrial superoxide production in the thyroid.

Keywords: Iodides; Metallothionein I/II knockout; Perchlorate; Propylthiouracil; Thyrotropin

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