Metallothionein-I/II Knockout Mice Aggravate Mitochondrial Superoxide Production and Peroxiredoxin 3 Expression in Thyroid after Excessive Iodide Exposure

Abstract

Purpose. We aim to figure out the effect of metallothioneins on iodide excess induced oxidative stress in the thyroid. Methods. Eight-week-old MT-I/II knockout (MT-I/II KO) mice and background-matched wild-type (WT) mice were used. Mitochondrial superoxide production and peroxiredoxin (Prx) 3 expression were measured. Results. In in vitro study, more significant increases in mitochondrial superoxide production and Prx 3 expression were detected in the MT-I/II KO groups. In in vivo study, significantly higher concentrations of urinary iodine level were detected in MT-I/II KO mice in 100 HI group. Compared to the NI group, there was no significant difference existing in serum thyroid hormones level in either groups (P > 0.05), while the mitochondrial superoxide production was significantly increased in 100 HI groups with significantly increased LDH activity and decreased relative cell viability. Compared to WT mice, more significant changes were detected in MT-I/II KO mice in 100 HI groups. No significant differences were detected between the NI group and 10 HI group in both the MT-I/II KO and WT mice groups (P > 0.05). Conclusions. Iodide excess in a thyroid without MT I/II protection may result in strong mitochondrial oxidative stress, which further leads to the damage of thyrocytes.

Activation of the Nrf2-Keap 1 Pathway in Short-Term Iodide Excess in Thyroid in Rats

“…This is consistent with our previous study on metallothionein-I/II knockout mice [24]. Joanta et al reported that the initiation of free radical production was observed after giving a high dose of iodide [3].…”

“…We displayed that 10 mU/mL TSH can inhibit excessive iodide-induced strong mitochondrial superoxide production [55]. MT-I and MT-II are mainly involved in the protection of tissue against oxidative stresses; we indicated that metallothionein-I/II knockout mice aggravated mitochondrial superoxide production in thyroid after excessive iodide exposure [24]. In addition, we demonstrated that both the oxidative stress and the antioxidative defense increased simultaneously after high dosages of iodide intake.…”

“…Collecting FL2 channel forward scattering (forward scatter, FSC) and lateral scattering (side scatter, SSC) data, 10000 cells were collected for each sample. The control group without MitoSOX was regarded as the blank zero group for standardization [24]. …”

Reappraisal of metallothionein: Clinical implications for patients with diabetes mellitus

“…Metallothionein can be induced in the mammalian liver by Zn, and is upregulated by various forms of OS, such as ischemia–reperfusion injury with increasing levels of ROS and RNS, and excess concentrations of various metal ions . The promoter region of the MT gene contains antioxidant‐ and metal‐responsive elements (ARE and MRE, respectively) .…”

“…Under conditions of excess Zn, MT acts as a Zn chelator, but when OS or nitrosative stress are elevated MT behaves as a scavenger of ROS and RNS . Therefore, binding with Zn stabilizes MT, and OS also triggers Zn to integrate with thionein .…”