Nitric oxide is involved in the hypothyroidism with significant morphology changes in female Wistar rats induced by chronic exposure to high water iodine from potassium iodate.

Epidemiological studies indicated that chronic exposure to high water iodine is associated with primary hypothyroidism (PH) and subclinical hypothyroidism (SCH). However, the mechanism is not well understood. In this study, we explored whether chronic exposure to high water iodine from potassium iodate (KIO3) can induce hypothyroidism in addition to determining if nitric oxide (NO) is involved in the pathogenesis. 96 female Wistar rats were divided into six groups: control, I1000µg/L, I3000µg/L, I6000µg/L, N-nitro-L-arginine methylester (L-NAME) and L-NAME+I6000µg/L. After 3 months, urine iodine concentration, thyroid hormone, NO and nitric oxide synthase (NOS) serum levels were determined. Additionally, thyroid expression of inducible nitric oxide synthase (iNOS) was also investigated. Thyroid morphology was observed under light microscopy and transmission electron microscope. SCH as indicated by elevated serum thyrotropin (TSH) was induced among rats exposed to 3000 µg/L I-, while rats treated with 6000 µg/L I- presented PH characterized by elevated TSH and lowered total thyroxine in serum. Moreover, serum NO, NOS and iNOS expression in the thyroid were significantly increased in I3000µg/L and I6000µg/L groups. Changes in thyroid function and morphology in the L-NAME+I6000µg/L group were extenuated compared to I6000µg/L group. These findings suggested that chronic exposure to high water iodine from KIO3 likely induces hypothyroidism with significant morphology changes in female Wistar rats and NO appears to be involved in the pathogenesis.

Sodium Arsenite-Induced Learning and Memory Impairment Is Associated with Endoplasmic Reticulum Stress-Mediated Apoptosis in Rat Hippocampus.

Chronic arsenic exposure has been associated to cognitive deficits. However, mechanisms remain unknown. The present study investigated the neurotoxic effects of sodium arsenite in drinking water over different dosages and time periods. Based on results from the Morris water maze (MWM) and morphological analysis, an exposure to sodium arsenite could induce neuronal damage in the hippocampus, reduce learning ability, and accelerate memory impairment. Sodium arsenite significantly increased homocysteine levels in serum and brain. Moreover, sodium arsenite triggered unfolded protein response (UPR), leading to the phosphorylation of RNA-regulated protein kinase-like ER kinase (PERK) and eukaryotic translation initiation factor 2 subunit α (eIF2α), and the induction of activating transcription factor 4 (ATF4). Arsenite exposure also stimulated the expression of the endoplasmic reticulum (ER) stress markers, glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP) and the cleavage of caspase-12. Furthermore, exposure to arsenite enhanced apoptosis as demonstrated by expression of caspase-3 and TUNEL assay in the hippocampus. The results suggest that exposure to arsenite can significantly decrease learning ability and accelerate memory impairment. Potential mechanisms are related to enhancement of homocysteine and ER stress-induced apoptosis in the hippocampus.