In vitro study of acute toxic effects of high iodide doses in human thyroid follicles.

Abstract

The acute effects of increasing doses of sodium iodide were studied on human thyroid follicles isolated from normal paranodular tissue. After 24 h incubation in culture medium, follicles isolated from most thyroids maintained their capacity for 125I accumulation and organification and a normal cellular ultrastructure. 125I accumulation was significantly increased after addition of TSH, whereas 125I organification was not affected. In presence of TSH, numerous follicles had large empty-looking follicular lumina unlabeled on autoradiographies. Follicles incubated for 24 h in the presence of a low concentration (10(-7) M) of iodide retained their function and morphology. However, incubation with a high dose of iodide (10(-3) M) caused marked inhibition of 125I accumulation and organification reaching values similar to those obtained in presence of inhibitors of iodide trapping and organification. At high doses, iodide induced necrosis of thyroid epithelial cells: the percentage of necrotic cells was significantly increased with 10(-5) M and doubled with 10(-3) M as compared to values measured at 10(-7) M. Ultrastructural lesions such as apical blebbing, cytoplasmic fragments desquamation, endoplasmic reticulum vesiculation, and accumulation of lipofuscin in secondary lysosomes were also present. The necrotic effect and the ultrastructural alterations also occurred in the presence of TSH but were prevented by the addition of inhibitors of iodide trapping or organification. These results demonstrate a direct acute toxic effect of iodide in human thyroid cells. The nature of the ultrastructural alterations is in agreement with a mechanism of toxicity involving a free radical attack and lipid peroxidation as observed in other tissues.

Differential Regulation of the Production of Reactive Oxygen Species in Th1 Cytokine–Treated Thyroid Cells

“…As in nonstimulated conditions (19), and in accordance with the theory of redox homeostasis (53), the oxidative stress (OS) to which growing thyrocytes are exposed is harmless, likely because most of it is efficiently detoxified by the well-adapted antioxidant defenses (56,62). In pathological situations, including those simulated in models of iodine-induced thyroid involution (11,(22)(23)(24)(25)(26)63), a higher degree of OS occurs. This intense OS originates from two sources, including the thyrocytes themselves and the numerous interstitial inflammatory cells.…”

“…ROS are also involved in the hypoxia-inducible factor-mediated vascular endothelial growth factor pathway that is activated in thyrocytes in response to iodine shortage, which makes the endothelial compartment closely related to epithelial cells within the angiofollicular units (16,20,21). Other ROS, including hydroxyl radical (OH ), anion superoxide (O 2 -), peroxynitrite (ONOO -), and iodocompounds, are more reactive and sometimes toxic, as demonstrated in animal models of iodineinduced thyroid involution and in the nonobese diabetic mouse model of spontaneous autoimmune destructive thyroiditis (22)(23)(24)(25)(26).…”

Cell necrosis and apoptosis are differentially regulated during goitre development and iodine-induced involution

“…Significant differences between means were performed after ANOVA by the least significant differences test. The overall variation coefficient of the point counting method was about 6% (Many et al 1992). For morphometric analysis, differences were considered as significant when P<0·05 (not significant=ns).…”

“…The second thyroid lobe was carefully dissected, weighed and processed for light and electron microscopy (Many et al 1992); after a further fixation in the same fixative, thyroid fragments were postfixed in 1% osmium tetroxide, dehydrated and embedded in plastic. Semi-thin sections (0·5 µm) were cut from the centre of each fragment and stained with toluidine blue.…”

“…An acute toxic effect of iodide has been demonstrated in vivo in hypothyroid hamsters (Follis 1964), dogs (Belshaw & Becker 1973), mice (Wollman et al 1968, Mahmoud et al 1986) and rats (van den HoveVandenbroucke et al 1982, Contempré et al 1995, in obese chicken (Bagchi et al 1995) and in human thyroid follicles in vitro (Many et al 1992).…”