The protective effect of iodide intake adjustment and 1,25(OH)₂D₃ supplementation in rat offspring following excess iodide intake

Abstract

Background: In this study, we aimed to investigate the effect of iodide intake adjustment, 1,25(OH)2D3 supplementation, or both, on the thyroid gland of rat offspring. Methods: The offspring of female rats administered 100 times the normal dose of iodide (100 HI; 750 μg/d) during pregnancy and lactation were divided into four different treatment groups. They were either having their iodide intake adjusted from 100 HI to normal iodide intake (7.5 μg/day) or supplemented with 25-hydroxy vitamin D3 [1,25(OH)2D3; 5 μg·kg−1·day−1], or both, for 4 weeks. Thyroid sodium pertechnetate (Na99mTcO4) uptake percentages were measured using single-photon emission computed tomography, while serum levels of free triiodothyronine (FT3), free thyroxine (FT4), thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), and vitamin D3 (VD3) were monitored using enzyme-linked immunosorbent assay. The messenger ribonucleic acid expression of interleukin (IL)-17A, interferon gamma (IFN-γ), and IL-10 in the thyroid gland was measured using quantitative real-time polymerase chain reaction, while the protein expression of thyroid-hormone-receptor α1 (TRα1) and thyroid-hormone-receptor β1 (TRβ1) in the thyroid gland was detected using Western blotting. Haematoxylin and eosin (H & E) and immunofluorescence staining were also used to assess thyroid follicular structure and lymphocytic infiltration in the thyroid glands. Results: The immunofluorescence staining showed CD4+ co-localized with TRβ1 or the vitamin D receptor in thyroid gland cells of rats that were continuously treated with 100 HI. Following iodide adjustment, 1,25(OH)2D3 supplementation, or both, an increase in serum levels of FT3, free thyroxine, and VD3, protein expression of TRα1 and TRβ1 in the thyroid gland cells, and Na99mTcO4 thyroid uptake percentages was observed. The mRNA expression levels of IL-17A and IFN-γ, decreased, while the mRNA expression levels of IL-10 increased in the thyroid cells of each treatment group, except the group with continuous 100 HI intake. Conclusion: Iodide adjustment, 1,25(OH)2D3 supplementation, or both may increase the serum levels of FT3, FT4, and VD3, as well as the protein expression levels of TRα1 and TRβ1, in thyroid cells. In addition, iodide adjustment, 1,25(OH)2D3 supplementation, or both, may potentially reverse the imbalance in pro-inflammatory and anti-inflammatory cytokines (IL-17A, IFN-γ, and IL-10) caused by 100 HI, which may be beneficial in improving Na99mTcO4 thyroid uptake percentages.

Iodide intake during pregnancy and lactation stimulates KLF9, BDNF expression in offspring brain with elevated DHA, EPA metabolites

“…In our previous study, Wang et al demonstrated that Wistar rats received normal diet and deionized water in the normal iodide intake group. Therefore, the intake of iodide was 7.5 μg/day [ 19 ]. Liang et al reported that pregnant Wistar rats in normal iodide intake group consumed deionized water and a normal diet, resulting in daily iodide intake of 7.5 μg/d [ 16 ].…”

Increased Epoxyeicosatrienoic Acids and Hydroxyeicosatetraenoic Acids After Treatment of Iodide Intake Adjustment and 1,25-Dihydroxy-Vitamin D3 Supplementation in High Iodide Intake–Induced Hypothyroid Offspring Rats

“…Therefore, the intake of iodide was 750 μg/day (Wang et al, 2018 ). The rats in groups 3 and 5 were supplemented with 1,25(OH) 2 D 3 (MedChemExpress, Monmouth Junction, NJ, USA) by gavage (5 μg·kg −1 ·day −1 ) (Wang et al, 2020 ). The animal study was reviewed and approved by the Institutional Animal Care and Use Committee of Tianjin Medical University (No.…”

“…Our study has shown that 100 HI [i.e., potassium iodide (KI)] during the pregnancy and lactation period of rats can induce the decrease of FT3, FT4, and vitamin D3 (VD3) and also the increase of thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) levels in offspring at PN120. In addition, we demonstrated the protective effect of iodide intake adjustment, 1,25-dihydroxy-vitamin D 3 [1,25(OH) 2 D 3 ] supplementation, or both in offspring rats following excess iodide intake (Wang et al, 2020 ). Hypothyroidism is a commonly encountered clinical condition, and it can impact cardiac function (Klein and Danzi, 2007 ; Udovcic et al, 2017 ), blood pressure (Klein and Danzi, 2007 ), lipid parameters (Jabbar et al, 2017 ), and vitamin D level (Salma et al, 2020 ).…”

Thyroid and Heart: A Fatal Pathophysiological Attraction in a Controversial Clinical Liaison

“…Moreover, vitamin D administration may increase the serum levels of fT3 and fT4 in offspring of female rats administered 100 times the normal dose of iodide (100 HI; 750 µg/d) during pregnancy and lactation, as well as the protein expression levels of TRα1 and TRβ1 in their thyroid cells. In addition, 1,25(OH)2D3 supplementation reverses the imbalance in proinflammatory and anti-inflammatory cytokines (IL-17A, IFN-γ, and IL-10) [66]. At clinical levels, there is evidence of a relationship between vitamin D [25(OH)D] deficiency and autoimmune thyroid diseases or cancer, as well as between 25(OH)D levels and titers of antibodies and thyroid autoimmunity replacement, although some studies reported a lack of association [67,68].…”