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肌醇和硒可拮抗镉诱导的小鼠甲状腺 C 细胞增生和肥大。

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

机构信息

Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.

Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.

出版信息

Front Endocrinol (Lausanne). 2021 Feb 25;12:608697. doi: 10.3389/fendo.2021.608697. eCollection 2021.

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.

摘要

先前的研究表明,镉 (Cd) 除了会引起甲状腺滤泡的结构变化外,还会增加 C 细胞的数量。我们研究了肌醇 (MI)、硒代蛋氨酸 (Se)、MI+Se 和白藜芦醇对暴露于氯化镉 (CdCl2) 的小鼠 C 细胞的影响,因为目前尚无关于这些分子可能具有保护作用的相关数据。相比之下,我们之前已经证明了 MI+Se 对小鼠甲状腺滤泡具有这种保护作用。98 只 C57BL/6J 成年雄性小鼠被分为 14 组,每组 7 只:(i)0.9%NaCl(载体;1ml/kg/天腹腔注射);(ii)Se(0.2mg/kg/天口服);(iii)Se(0.4mg/kg/天口服);(iv)MI(360mg/kg/天口服);(v)Se(0.2mg/kg/天)+MI;(vi)Se(0.4mg/kg/天)+MI;(vii)白藜芦醇(20mg/kg);(viii)CdCl2(2mg/kg/天腹腔注射)+载体;(ix)CdCl2+Se(0.2mg/kg/天);(x)CdCl2+Se(0.4mg/kg/天);(xi)CdCl2+MI;(xii)CdCl2+Se(0.2mg/kg/天)+MI;(xiii)CdCl2+Se(0.4mg/kg/天)+MI;(xiv)CdCl2+白藜芦醇(20mg/kg)。14 天后,对甲状腺进行组织学、免疫组织化学和形态计量学评估。与载体相比,Cd 显著降低了滤泡的平均直径,增加了 CT 阳性细胞的数量、面积和细胞质密度,并导致 TUNEL 阳性 C 细胞的消失,即正在凋亡的 C 细胞的消失。每天 0.2 或 0.4mg/kg 的 Se 未能显著增加滤泡的平均直径,轻度降低 CT 阳性细胞的数量、面积和细胞质密度,对 TUNEL 阳性 C 细胞无效。相反,MI 单独使用可显著增加滤泡的平均直径和 TUNEL 阳性细胞的数量,并显著降低 CT 阳性细胞的数量、面积和细胞质密度。MI+Se 0.2mg/kg/天或 MI+Se 0.4mg/kg/天的给药更显著地改善了所有五个指标。事实上,滤泡的平均直径和 TUNEL 阳性细胞的数量显著增加,而 CT 阳性细胞的数量、面积和细胞质密度显著降低。因此,所有五个指标都与载体处理的小鼠重叠。白藜芦醇显著改善了所有考虑的参数,其效果与 MI 相当。总之,肌醇+Se 的联合作用可有效保护小鼠甲状腺免受 Cd 引起的 C 细胞增生和肥大。这种益处增加了肌醇+Se 对甲状腺细胞和睾丸的益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03a4/7949001/163802c10710/fendo-12-608697-g001.jpg

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