长期暴露于NaAsO2会诱发Sprague-Dawley大鼠甲状腺功能障碍和炎症损伤,NLRP3炎性体介导的热蛋白沉积参与其中。

IF 4.8 2区 医学 Q1 TOXICOLOGY Archives of Toxicology Pub Date : 2024-08-09 DOI:10.1007/s00204-024-03837-9
Lili Fan, Qian Song, Ying Jin, Rui He, Heng Diao, Peng Luo, Dapeng Wang
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引用次数: 0

摘要

砷是一种众所周知的有害有毒物质,近年来发现它是一种环境内分泌干扰物,会在各种内分泌器官中蓄积,阻碍这些器官的正常生理功能,改变激素分泌水平。此外,一些研究表明,砷暴露与甲状腺功能之间存在相关性,这表明砷对甲状腺有毒害作用。然而,人们对砷暴露导致甲状腺损伤的具体类型及其潜在的分子机制仍然知之甚少。本研究调查了不同剂量(0、2.5、5.0 和 10.0 毫克/千克体重)和不同持续时间(12、24 和 36 周)的亚砷酸钠(NaAsO2)暴露对斯普拉格-道利(SD)大鼠甲状腺组织和甲状腺激素水平的毒性效应,并探讨了这些效应的具体机制。我们的结果表明,暴露于二氧化钠可导致该元素在大鼠甲状腺组织中的积累。更重要的是,长期暴露于NaAsO2会显著上调甲状腺组织中NLRP3炎性体相关蛋白的表达,导致甲状腺细胞发生热凋亡,进而引起SD大鼠甲状腺功能障碍、炎性损伤、上皮-间质转化(EMT),甚至纤维化改变。这些发现加深了我们对砷暴露对甲状腺及其功能的毒性影响的了解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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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.

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来源期刊
Archives of Toxicology
Archives of Toxicology 医学-毒理学
CiteScore
11.60
自引率
4.90%
发文量
218
审稿时长
1.5 months
期刊介绍: Archives of Toxicology provides up-to-date information on the latest advances in toxicology. The journal places particular emphasis on studies relating to defined effects of chemicals and mechanisms of toxicity, including toxic activities at the molecular level, in humans and experimental animals. Coverage includes new insights into analysis and toxicokinetics and into forensic toxicology. Review articles of general interest to toxicologists are an additional important feature of the journal.
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