title: Propylthiouracil, Perchlorate, and Thyroid-Stimulating Hormone Modulate High Concentrations of Iodide Instigated Mitochondrial Superoxide Production in the Thyroids of Metallothionein I/II Knockout Mice.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathophysiology, School of Basic Medical Science, Tianjin Medical University, Tianjin, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Duan
authors.affiliation: Department of Pathophysiology, School of Basic Medical Science, Tianjin Medical University, Tianjin, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, School of Basic Medical Science, Tianjin Medical University, Tianjin, China.
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, School of Basic Medical Science, Tianjin Medical University, Tianjin, China.
authors.forename: Vern
authors.initials: V
authors.lastname: Perera
authors.affiliation: Department of Pathophysiology, School of Basic Medical Science, Tianjin Medical University, Tianjin, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Pathophysiology, School of Basic Medical Science, Tianjin Medical University, Tianjin, China.
authors.forename: Iruni Roshanie
authors.initials: IR
authors.lastname: Abeysekera
authors.affiliation: Department of Pathophysiology, School of Basic Medical Science, Tianjin Medical University, Tianjin, China. jupx@163.com.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Yao
keywords: Iodides; Metallothionein I/II knockout; Perchlorate; Propylthiouracil; Thyrotropin