Role of iodine in pathogenesis of thyroid disease - is induction of apoptosis consequence of iodine cytotoxicity?

Abstract

Iodine is one of the best-characterized environmental factors associated with autoimmune thyroid disease (ATD). Epidemiological studies have shown that ATD incidence has increased following the introduction of salt iodination in the 1920s; in addition, ATD patients can improve upon iodine restriction. In animal models such as BioBreeding/Worcester and Buffalo rats, obese chicken strain, and non-obese diabetic H-2h4 mice, excess iodine is associated with autoimmunity. Analyses of Hashimoto thyroiditis (HT) have shown enlarged number of apoptotic follicular cells, and the destruction is an effect of death receptormediated apoptosis. Excess of iodine induces rapid apoptosis of goitrogen Wistar pretreated rats, possibly connected with inhibition of polyamine synthesis, inhibitors of DNA fragmentation. Percentage of apoptotic cells was statistically higher in patients with HT than in those with euthyroid goiter, with significant increase of caspase 32. Genes for Bcl-2 and Bax proteins are under the transcriptional control of p53. In TAD-2 cell cultures, apoptosis is p53-independed, suggesting that DNA damage is not primarily evoked by potassium iodide (KI). High concentrations of NaI increase the proportion of apoptotic cells in FTRL5 thyroid cell line. Iodide cytotoxicity is inhibited by a TPO inhibitor and is relieved with an anti-oxidant agent. Chronic iodine excess induces apoptosis and necrosis of thyroid follicular and endothelial cells, leading to thyroglobulin accumulation in connective tissue. Iodide excess requires peroxidase enzymatic activity to induce apoptosis. Ionic iodide is not directly toxic, whereas its molecular form I2 mediates the apoptotic effect of KI. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. OI-175059]

Iodine Conjugated Pt(IV) Nanoparticles for Precise Chemotherapy with Iodine–Pt Guided Computed Tomography Imaging and Biotin-Mediated Tumor-Targeting

“…Iodine reversed the Pt-based drug resistance of A549/DDP, indicating enhanced anticancer ability and great potential for clinical application of Bio-Pt-I NPs. The expression levels of apoptosis-related Bcl-2 protein in tumor cells were detected to explore the mechanism of the enhanced cytotoxicity, especially in cisplatin-resistant cells. Among several kinds of nanomedicines in our experiments, only iodine-containing drugs effectively inhibited the expression of Bcl-2 protein in MCF-7 cells.…”

Impact of iodine intake on the pathogenesis of autoimmune thyroid disease in children and adults

“…Excessive iodine intake is a risk factor for thyroid diseases, including AITD, and certain people are more susceptible, including the elderly, pregnant women, fetuses, and neonates, as well as those with pre-existing goiters or iodine deficiency. Either a deficit or excess of iodine may increase the incidence of thyroid disease, and iodine intakes should be maintained within a limited optimal range [ 9 ]. A daily intake of ~150–300 g of iodine is recommended by the World Health Organization (WHO; corresponding to a median urine iodine concentration of 100–199 g/L).…”