Arsenic is a ubiquitous hazardous metalloid that poses a significant threat to human health. Although researchers have investigated the detrimental effects of arsenic on the thyroid, a comprehensive exploration of its toxicological impact and underlying molecular mechanisms remains to be conducted. Both this study and our previous reports demonstrated that chronic exposure to sodium arsenite (NaAsO2) results in histological impairment and dysfunction of the thyroid glands in Sprague-Dawley (SD) rats. Proteomic and phosphoproteomic analyses were performed to investigate the molecular mechanisms underlying the effects of chronic NaAsO2 exposure on thyroid function in SD rats. NaAsO2 disrupts the synthesis of thyroid hormones (THs) and alters the expression of the THs-synthesizing enzyme dual oxidase 2. In addition, oxidative phosphorylation, the AMP-activated protein kinase signaling pathway, central carbon metabolism in cancer, cysteine and methionine metabolism, cellular response to heat stress, and protein processing in the endoplasmic reticulum were upregulated, whereas glutathione metabolism was downregulated. In conclusion, this study revealed thyroid damage in SD rats induced by chronic NaAsO2 exposure and elucidated the disrupted molecular pathways, thereby providing novel insights into the molecular mechanisms underlying arsenic exposure and its impact on thyroid function.

中文翻译：

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长期暴露于高剂量 NaAsO₂ 大鼠的分子紊乱和甲状腺功能障碍：来自蛋白质组学和磷酸化蛋白质组学分析的见解


砷是一种无处不在的危险准金属，对人类健康构成重大威胁。尽管研究人员已经调查了砷对甲状腺的有害影响，但对其毒理学影响和潜在分子机制的全面探索仍有待进行。这项研究和我们之前的报告都表明，长期暴露于亚砷酸钠 （NaAsO2） 会导致 Sprague-Dawley （SD） 大鼠的组织学损伤和甲状腺功能障碍。进行蛋白质组学和磷酸化蛋白质组学分析，探讨慢性 NaAsO2 暴露对 SD 大鼠甲状腺功能影响的分子机制。NaAsO2 破坏甲状腺激素 （THs） 的合成并改变 THs 合成酶双氧化酶 2 的表达。此外，氧化磷酸化、AMP 活化蛋白激酶信号通路、癌症中的中心碳代谢、半胱氨酸和蛋氨酸代谢、细胞对热应激的反应以及内质网中的蛋白质加工上调，而谷胱甘肽代谢下调。总之，本研究揭示了慢性 NaAsO2 暴露诱导的 SD 大鼠甲状腺损伤，并阐明了被破坏的分子途径，从而为砷暴露的分子机制及其对甲状腺功能的影响提供了新的见解。