Molecular Disturbances and Thyroid Gland Dysfunction in Rats Chronically Exposed to a High Dose of NaAsO₂: Insights from Proteomic and Phosphoproteomic Analyses

Abstract

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.