Nitrates are natural compounds present in soil and water; however, the intense use of fertilizers has increased their presence in groundwater with deleterious effects on human health. There is evidence of nitrates acting as endocrine disruptors; however, the underlying molecular mechanisms have not been fully described. Here, we investigated the effect of subchronic exposure to different concentrations of sodium nitrate in female Wistar rats, evaluating thyroid hormonal parameters, such as Nis transporter (Na⁺/I⁻ symporter, Slc5a5) and Tsh-R receptor protein expression, as well as transcription of the Tpo (thyroperoxidase), Tg (tiroglobulin), Duox2 (dual oxidase 2), Pds (pendrin), and Mct8 (Mct8 transporter, Slc16a2) genes. Hematological and histochemical changes in the liver and thyroid were also explored. Significant differences were found in platelet and leukocyte counts; although a significant increase in the weight of the thyroid gland was observed, no differences were found in the levels of the hormones Tsh, T3, and T4, but a modulation of the mRNA expression of the Tg, Tpo, Duox2, Mct8, and Pds genes was observed. Morphological changes were also found in liver and thyroid tissue according to the exposure doses. In conclusion, subchronic exposure to sodium nitrate induces leukocytosis consistent with an inflammatory response and upregulation of Sod2 in the liver and increases the expression of genes involved in the synthesis of thyroid hormones, keeping thyroid hormone levels stable. Histological changes in the thyroid gland suggest a goitrogenic effect.

中文翻译：

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亚慢性暴露于硝酸钠的雌性 Wistar 大鼠参与甲状腺激素合成的 Tpo、Tg、Duox2、Pds 和 Mct8 基因的调节

硝酸盐是存在于土壤和水中的天然化合物；然而，化肥的大量使用增加了它们在地下水中的存在，对人类健康产生有害影响。有证据表明硝酸盐是内分泌干扰物；然而，潜在的分子机制尚未完全描述。在这里，我们研究了雌性 Wistar 大鼠亚慢性暴露于不同浓度硝酸钠的影响，评估甲状腺激素参数，如 Nis 转运蛋白（Na ⁺ /I ^-同向转运蛋白，Slc5a5）和 Tsh-R 受体蛋白表达，以及的转录的Tpo（甲状腺过氧化物酶），Tg为（tiroglobulin），DUOX2（双氧化酶2），PDS（pendrin）和Mct8（Mct8 转运蛋白，Slc16a2）基因。还研究了肝脏和甲状腺的血液学和组织化学变化。血小板和白细胞计数存在显着差异；虽然观察到甲状腺重量显着增加，但激素 Tsh、T3 和 T4 的水平没有差异，但Tg、Tpo、Duox2、Mct8和Pds的 mRNA 表达有所调节基因被观察到。根据暴露剂量，肝脏和甲状腺组织中也发现了形态学变化。总之，亚慢性暴露于硝酸钠会诱导白细胞增多，这与炎症反应和Sod2 的上调一致在肝脏中增加参与甲状腺激素合成的基因表达，保持甲状腺激素水平稳定。甲状腺的组织学变化表明有致甲状腺肿的作用。