Regulation of the Tpo, Tg, Duox2, Pds, and Mct8 genes involved in the synthesis of thyroid hormones after subchronic exposure to sodium nitrate in female Wistar rats

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.