Prolonged exposure to NaAsO2 induces thyroid dysfunction and inflammatory injury in Sprague‒Dawley rats, involvement of NLRP3 inflammasome‒mediated pyroptosis.

Arsenic, a well-known hazardous toxicant, has been found in recent years to act as an environmental endocrine disruptor that accumulates in various endocrine organs, impeding the normal physiological functions of these organs and altering hormone secretion levels. Moreover, some research has demonstrated a correlation between arsenic exposure and thyroid functions, suggesting that arsenic has a toxicological effect on the thyroid gland. However, the specific type of thyroid gland damage caused by arsenic exposure and its potential molecular mechanism remain poorly understood. In this study, the toxic effects of sodium arsenite (NaAsO2) exposure at different doses (0, 2.5, 5.0 and 10.0 mg/kg bw) and over different durations (12, 24 and 36 weeks) on thyroid tissue and thyroid hormone levels in Sprague‒Dawley (SD) rats were investigated, and the specific mechanisms underlying the effects were also explored. Our results showed that NaAsO2 exposure can cause accumulation of this element in the thyroid tissue of rats. More importantly, chronic exposure to NaAsO2 significantly upregulated the expression of NLRP3 inflammasome-related proteins in thyroid tissue, leading to pyroptosis of thyroid cells and subsequent development of thyroid dysfunction, inflammatory injury, epithelial-mesenchymal transition (EMT), and even fibrotic changes in the thyroid glands of SD rats. These findings increase our understanding of the toxic effects of arsenic exposure on the thyroid gland and its functions.