The Association of Myo-Inositol and Selenium Contrasts Cadmium-Induced Thyroid C Cell Hyperplasia and Hypertrophy in Mice

Abstract

Previous studies have demonstrated that, in addition to inducing structural changes in thyroid follicles, cadmium (Cd) increased the number of C cells. We examined the effects of myo-inositol (MI), seleno-L-methionine (Se), MI + Se, and resveratrol on C cells of mice exposed to cadmium chloride (Cd Cl2), as no data are currently available on the possible protective effects of these molecules. In contrast, we have previously shown this protective effect against CdCl2 on the thyroid follicles of mice. Ninety-eight C57 BL/6J adult male mice were divided into 14 groups of seven mice each: (i) 0.9% NaCl (vehicle; 1 ml/kg/day i.p.); (ii) Se (0.2 mg/kg/day per os); (iii) Se (0.4 mg/kg/day per os); (iv) MI (360 mg/kg/day per os); (v) Se (0.2 mg/kg/day) + MI; (vi) Se (0.4 mg/kg/day) + MI; (vii) resveratrol (20 mg/kg); (viii) CdCl2 (2 mg/kg/day i.p.) + vehicle; (ix) CdCl2 + Se (0.2 mg/kg/day); (x) CdCl2 + Se (0.4 mg/kg/day); (xi) CdCl2 + MI; (xii) CdCl2 + Se (0.2 mg/kg/day) + MI; (xiii) CdCl2 + Se (0.4 mg/kg/day) + MI; (xiv) CdCl2 + resveratrol (20 mg/kg). After 14 days, thyroids were processed for histological, immunohistochemical, and morphometric evaluation. Compared to vehicle, Cd significantly decreased follicle mean diameter, increased CT-positive cells number, area and cytoplasmic density, and caused the disappearance of TUNEL-positive C cells, namely, the disappearance of C cells undergoing apoptosis. Se at either 0.2 or 0.4 mg/kg/day failed to significantly increase follicular mean diameter, mildly decreased CT-positive cells number, area and cytoplasmic density, and was ineffective on TUNEL-positive C cells. Instead, MI alone increased significantly follicular mean diameter and TUNEL-positive cells number, and decreased significantly CT-positive cells number, area and cytoplasmic density. MI + Se 0.2 mg/kg/day or MI + Se 0.4 mg/kg/day administration improved all five indices more markedly. Indeed, follicular mean diameter and TUNEL-positive cells number increased significantly, while CT-positive cells number, area and cytoplasmic density decreased significantly. Thus, all five indices overlapped those observed in vehicle-treated mice. Resveratrol improved significantly all the considered parameters, with a magnitude comparable to that of MI alone. In conclusion, the association Myo + Se is effective in protecting the mouse thyroid from the Cd-induced hyperplasia and hypertrophy of C cells. This benefit adds to that exerted by Myo + Se on thyrocytes and testis.

Sarcoglycans and integrins in human thyrocytes: an immunofluorescence study

“…Extracellular domains of the integrins, a known family of transmembrane glycoproteins, interact with a variety of ligands (35), including extracellular matrix glycoproteins, and the intracellular domain linked to the cytoskeleton (36). Moreover, it has been demonstrated that the thyroid hormone could influence the interaction of integrins with the extracellular matrix protein (22). At this purpose, αvβ3-integrin has a large number of extracellular protein ligands, including growth factors and extracellular matrix proteins.…”

“…Based on our previous results in epithelial and glandular tissues, in the present report we performed a study on SGs and integrins in thyrocytes. In particular, we studied all SGs and the αvβ3-integrin, a cell surface receptor for thyroid hormone, which is the initiation site for T4-induced activation of intracellular signalling cascades (21) by activation of the sodium pump (14,22). As this integrin is also widely present on cancer cells, it was clear that the thyroid hormone has also been found to cause proliferation of a variety of human cancer lines via the cell surface receptor.…”

Trace elements and the thyroid

“…Cadmium (Cd) is listed as one of 126 priority pollutants and a kind of carcinogen. There are insufficient studies on its effects on the thyroid, but it has been reported that chronic Cd poisoning is common in cases of colloid cystic goiter, adenomatous follicular hyperplasia with low dysplasia and reduced Tg secretion, and diffuse nodular hyperplasia and hypertrophy of parafollicular cells ( 132 – 134 ).…”