Toxic effects of iodide and iodized oil on mouse hyperplastic goiter
(1986)
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- In the first part of this work, we give a general review of the literature. <BR> Chapter 1 comprises a description of the morphology of the normal thyroid gland and the different kinds of follicular cells. <BR> In chapter 2, we explained the different aspects of iodine metabolism and biosynthesis of thyroid hormones, with a special emphasis on very recent data on the Tg structure, obtained by studies on the Tg gene, and hormogenic sites. <BR> In chapter 3, we give a general glance on the different control and regulatory mechanisms, focusing mainly on the major regulatory factor, i.e. TSH. <BR> In chapter 4, we define and classify non-toxic goiter, describe the different pathophysiological mechanisms involved in its genesis, and the methods used for its prophylaxis and treatment. <BR> The second part comprises our personal work. <BR> In chapter 1, the experimental models and the different treatments are described, as well as the morphological, stereological, and functional procedures and techniques used to analyse the effect of iodine and lipiodol on iodine-deficient thyroid glands. <BR> In chapter 2, the morphological changes taking place in the thyroid after a goitrogenic treatment and after the administration of different doses of iodide and thyroid hormones are described. Iodide in excess induces a follicular epithelial necrosis in the hyper-plastic thyroid. This necrosis is characterized by the presence of excessive amounts of cell debris in the follicular lumina and of altered or necrotic cells in the epithelial wall of the follicles. The inflammatory infiltrate consist of polymorphonuclear and mononuclear cell types. Lipofuscin inclusions were observed in follicular cells. <BR> Neither necrosis nor inflammation were observed when a moderate dose of iodine, or T3, or T3+ a high iodine dose were administered. In contrast, cell deletion took place only through cell shrinkage, i.e. apoptosis, hereby described for the first time in the thyroid. After the administration of drugs interfering with iodination (PTU), no necrosis or inflammation were observed, whereas after the administration of drug preventing the vasoconstriction (papaverine), both lesions were found. <BR> From thos, we can conclude that the toxic effect of iodine on the follicular cells is direct and requires either oxidation or organification of iodide. More-over, this toxicity is dose dependent, since it is not found after MID supplementation to iodine-deficient animals, or after HID administration to control animals. <BR> Since iodine in a slowly resorbable form i.e. lipiodol is widely used for goiter prophylaxis and treatment, we tested the effects of a single im injection of lipiodol on ICR mouse and compared our results with those obtained with NaI. Our data are presented and discussed in chapter3. <BR> A single injection of lipiodol, with doses of iodine as low as 10 µg, corresponding to 2-4 mg in human, induced marked lesions, comprising follicular necrosis and inflammation, as with NaI. In addition, we found a necrotizing arteritis, exclusively in the thyroid arteries. Furthermore, a moderate dose on iodine given before the iodized oil injection protected the thyroid form follicular necrosis and inflammation, and reduced the incidence of arteritis. <BR> the finding of lipofuscin inclusions, soon after HID administration, led us to dram the hypothesis that iodide toxicity could be induces by free radicals, since lipofuscin inclusions are know to be the end-products of membrane peroxidation, a process induced by free radicals. <BR> We therefore tested, as presented in chapter 4, the effect of vitamin E, an antioxidant, on the hyperplastic thyroid during treatment with high doses of iodine. Vitamin E protected the thyroid from the inflammatory and epithelial necrotic lesions with no interference with the iodination or the coupling reactions. Free radicals formed in excess during administration of high doses of iodine are probably the cause of high doses of iodine are probably the cause for the follicular epithelial damage. They may also be involved in the induction of the acute inflammatory reaction taking place at early hours, whereas leakage of antigens from the necrosed cells may be the cause for the formation or autoantibodies and thus the mononuclear inflammation that takes place later
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Mahmoud, I. J. (1986). Toxic effects of iodide and iodized oil on mouse hyperplastic goiter. https://hdl.handle.net/2078.5/112010