The association between endothelial function and autoimmune thyroiditis induced by iodine excess.

BACKGROUND: Iodine excess (IE) intake leads to lymphocyte dysfunction and contributes to autoimmune thyroiditis (AIT). Abnormal thyroid function is associated with adverse cardiovascular events, endothelial dysfunction is often an early pathophysiological feature in most cardiovascular disease. However, the relationship between iodine and the cardiovascular system is currently unclear. Therefore, the aim of this study was to investigate the effects of IE on endothelial function in mouse model. METHODS: A total of 24 NOD.H-2h4 mice were randomly divided into different groups. A sodium iodide (NaI) group supplied with 0.05% NaI water for 8 weeks. Serum levels of tumor necrosis factors α (TNFα), interleukin-6 (IL-6) and C-reactive Protein (CRP), as well as endothelin-1 (ET-1), von Willebrand factor (VWF) and thrombomodulin (THBD) were detected by Elisa. In addition, the mRNA and protein expression of these genes were measured by RT-PCR and Western blotting. RESULTS: Here, we found the urinary iodine concentration (UIC) was higher in the NaI group compared to the control group. Serum levels of ET-1, VWF, and THBD were also significantly lower in the NaI group, however, CRP serum levels are significantly increased. In aorta, the mRNA and protein expression of ET-1, VWF, THBD were downregulated, however, the expression of IL-6, CRP and TNFα mRNA and protein were upregulated in the NaI group. A correlation analysis showed negative correlation between UIC with ET-1, VWF, and THBD, similarly, negative correlation between CRP with THBD was observed. In addition, positive correlations between UIC with CRP. CONCLUSION: Collectively, in the NOD.H-2h4 mice, IE supplementation had a suppressive effect on endothelial function, and this inhibition maybe due to the increase expression of inflammatory cytokines.

Iodine Excess May Lead to Low Exam Score in Children Aged 8-10 Years.

Recent research has shown that iodine excess may damage children's intelligence. Years of monitoring results in Shanghai show the iodine status has approached the upper limit of the appropriate range for children aged 8-10 years, indicating a risk of iodine excess. We used multi-stage random sampling to select children. Sixteen districts of Shanghai were divided into five units based on geographic location, and one primary school was randomly selected from each unit. In each selected school, about 40 children aged 8-10 years were randomly recruited to measure their urinary iodine concentration (UIC), household salt iodine concentration (SIC), the score of the final unified exam of the last semester, and school canteen salt iodine concentration. The median UIC of 3213 children aged 8-10 years in Shanghai was 195.4 (122.0, 285.8) µg/L and exceeded 200 µg/L in 48.8% of the population. Household and school canteen iodized salt coverage rates were 60.3% and 82.5% respectively, and mean household and school canteen SICs were 21.51 ± 9.30 mg/kg and 25.29 ± 3.40 mg/kg respectively. By correcting for potential confounding factors, logistic regression demonstrated that compared to the adequate iodine status group, students in the slight iodine excess group were less likely to get "A" (score > 90) in math, Chinese, and English exams (Math: OR = 0.775, 95% CI = 0.660-0.911, P = 0.002; Chinese: OR = 0.707, 95% CI = 0.543-0.842, P < 0.001; English: OR = 0.720, 95% CI = 0.610-0.849, P < 0.001). In Shanghai, the iodine status of 8-10-year-old children is approaching the upper limit of the adequate range. Iodine excess in Shanghai may lead to low exam scores for students.

The Role of Thyroid Hormone Synthesis Gene-Related miRNAs Profiling in Structural and Functional Changes of The Thyroid Gland Induced by Excess Iodine.

At recent years, the impairment caused by iodine excess are paid more attention. However, there is still largely unknown about the exact mechanism induced by excessive iodine. MiRNAs have been found to act as biomarkers for a variety of diseases, whereas fewer studies focused on miRNAs related to a cluster of genes regulating thyroid hormone synthesis, such as NIS, Pendrin, TPO, MCT8, TSHR, TSHα, and TSHß-related miRNAs in structural and functional changes of the thyroid gland induced by subchronic and chronic high iodine exposure. In the present study, one hundred and twenty 4-week-old female Wistar rats were randomly divided into control group (I50µg/L KIO3); HI 1 (I6000µg/L KIO3); HI 2 (I10000µg/L KIO3); and HI 3 (I50000µg/L KIO3), the exposure period was 3 months and 6 months, respectively. The iodine contents in the urine and blood, thyroid function, and pathological changes were determined. In addition, levels of thyroid hormone synthesis genes and the associated miRNAs profiling were detected. The results showed that subclinical hypothyroidism occurred in the high iodine groups with subchronic high iodine exposure, while 6-month exposure led to hypothyroidism in the I10000µg/L and I50000µg/L groups. Subchronic and chronic high iodine exposure caused mRNA and protein levels of NIS, TPO, and TSHR decreased significantly, and Pendrin expression increased significantly. In addition, MCT8 mRNA and protein levels are only remarkably decreased under the subchronic exposure. PCR results showed that levels of miR-200b-3p, miR-185-5p, miR-24-3p, miR-200a-3p, and miR-25-3p increased significantly exposed to high iodine for 3 months, while miR-675-5p, miR-883-5p, and miR-300-3p levels increased significantly under the exposure to high iodine for 6 months. In addition, miR-1839-3p level was markedly decreased exposed to high iodine for 3 and 6 months. Taken together, the miRNA profiling of genes regulating thyroid hormone synthesis remarkably altered from subclinical hypothyroidism to hypothyroidism induced by excess iodine exposure, and some miRNAs may play an important role in subclinical hypothyroidism or hypothyroidism through regulating NIS, Pendrin, TPO, MCT8, and TSHR providing promising targets to alleviate the impairment on the structure and function of thyroid gland.

Chronic Iodine Intake Excess Damages the Structure of Articular Cartilage and Epiphyseal Growth Plate.

This study aimed to explore the influence of excess iodine on the articular cartilage and epiphyseal growth plate in rats. Wistar rats (n = 200) were randomly divided into five groups with 40 rats in each: normal iodine (NI), 5-fold high iodine group (5HI), 10-fold high iodine group (10HI), 50-fold high iodine group (50HI), and 100-fold high iodine group (100HI). The rats were executed in 6 and 12 months. 24-h urinary iodine concentration (UIC) was monitored by arsenic-cerium catalytic spectrophotometry. The chemiluminescence method was used to determine the thyroid function. The pathological changes in the epiphyseal plate, articular cartilage, and thickness of the epiphyseal plate were observed. The mRNA expression of collagen II (ColII), collagen X, matrix metalloproteinase-13 (MMP-13), and fibroblast growth factor receptor 1 in articular chondrocytes was detected by RT-PCR. 24-h UIC increased as iodine intake increased. In the 12th month, there was a significant increase in serum sTSH and a decrease in serum FT4 in HI groups, compared to the NI group. There was a decrease in the number of proliferating cells in the epiphyseal plate and an increase in the number of mast cell layers. The chondrocytes appeared disorganized, and the tidal lines were disturbed or even broken. Growth plate thickness decreased with increasing iodine intake. Compared with the NI group, ColII and MMP-13 mRNA expression in chondrocytes in all HI groups significantly increased. Chronic iodine overdose increases the risk of hypothyroidism. Chronic iodine overdose leads to abnormal morphology of epiphyseal growth plates and articular cartilage, increasing the risk of osteoarthritis.

A study of programmed death-1/programmed death ligand and iodine-induced autoimmune thyroiditis in NOD.H-2h4 mice.

Excess iodine will trigger the occurrence of autoimmune thyroiditis (AIT), and programmed death-1 (PD-1)/programmed death ligand (PD-L) will also contribute to the development of AIT. The purpose of this study was to explore the role that negative regulatory signals mediated by PD-1/PD-L play in the development of spontaneous autoimmune thyroiditis (SAT) in NOD.H-2h4 mice when they are exposed to iodine. Programmed death ligand 1 (PD-L1) antibody was administered intraperitoneally to NOD.H-2h4 mice. The relevant indicators were determined by flow cytometry, real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, immunohistochemistry, pathological hematoxylin and eosin staining, and arsenic-cerium catalytic spectrophotometry. Results showed that the level of urinary iodine, the level of thyroid lymphocyte infiltration, the level of thyroglobulin antibodies (TgAb) and interferon (IFN-γ)/tumor necrosis factor (TNF-α)/interleukin (IL-2)/IL-17, and the relative expression of PD-1/PD-L1/programmed death-2 (PD-L2) increased with the intervention of excess iodine. After the intervention of the PD-L1 antibody, the expression of PD-1/PD-L1/PD-L2 in different degrees was inhibited, but the level of thyroid lymphocyte infiltration and serum TgAb/IFN-γ/TNF-α/ IL-2/IL-17 did not decrease. Collectively, although PD-1/PD-L participates in the occurrence of SAT and induces inflammation, administration of the PD-L1 antibody does not effectively improve the pathological process of SAT. More research is needed to determine whether PD-1/PD-L intervention can treat autoimmune thyroid disease.

Biological regulation on iodine using nano-starch for preventing thyroid dysfunction.

The growing incidence of thyroid disease triggered by excess iodine uptake poses a severe health threat throughout the world. Extracellular interference therapies impede iodine transport across the sodium-iodide symporter (NIS) membrane protein and thus prevent excessive iodine uptake by thyroid cells, which may lessen the occurrence of disease. Herein, we for the first time utilized nano-starch particles (St NPs) to regulate iodine transport across the NIS protein of thyroid cells by using extracellular interference therapy. By precisely encapsulating iodine within the cavity of a glucan α-helix via hydrogen bonding, extracellular St NPs prevented excess iodine uptake by thyroid cells in vitro and in vivo; this down-regulated the expression of NIS protein (0.06-fold) and autophagy protein LC3B-II (0.35-fold). We also found that St NPs regulated the metabolic pathway of iodine in zebrafish. We believe this proposed strategy offers a novel insight into controlling iodine uptake by the thyroid and indicates a new direction for preventing iodine-induced thyroid disease.

The Relationship Between Iodine Excess and Thyroid Function During Pregnancy and Infantile Neurodevelopment at 18-24 Months.

BACKGROUND: Thyroid disease is a prevalent condition during pregnancy, and excessive iodine intake can lead to changes in thyroid function. However, research on the relationship between maternal iodine excess, thyroid hormones during pregnancy, and infantile neurodevelopment is limited. OBJECTIVES: This study aimed to explore the relationship between maternal iodine excess and thyroid hormones during pregnancy and infantile neurodevelopment. The objective was to provide evidence to support and enhance the prevention of neurodevelopmental retardation in infants. METHODS: From 2016 to 2018, a prospective study was conducted from pregnancy to 18-24 mo postpartum. Maternal urinary iodine concentration (UIC), thyroid-stimulating hormone (TSH), total serum iodine (TSI), and nonprotein-bound serum iodine during pregnancy were determined. The Gesell Development Scale was used to assess neurodevelopment of infants aged 18-24 mo. The iodine status of pregnant females was divided into following 4 groups on the basis of the distribution of maternal UIC: <100 µg/L (moderate deficiency), 100-149 µg/L (mild deficiency), 150-249 µg/L (sufficiency), and >250 µg/L (above requirement). RESULTS: Our study included 469 mother-infant pairs. Compared with the maternal UIC of 150-249 µg/L during pregnancy, risk of adaptive developmental delay was increased in infants with maternal UIC ≥250 µg/L (OR: 2.38; 95% CI: 1.06, 5.35). Pregnant females with TSI >90th quantiles were more likely to have offspring with language developmental delay than those with lower TSI in 10th-90th quantiles (OR: 3.06; 95% CI: 1.09, 8.58). Risk of fine motor developmental delay was increased in infants with maternal TSH ≥2.5 mIU/L during pregnancy (OR: 4.32; 95% CI: 1.43, 13.0). CONCLUSIONS: Maternal iodine nutritional status above requirement (UIC ≥250 µg/L or TSI >90th quantiles) during pregnancy negatively affects infantile neurodevelopment. Maternal TSH ≥2.5 mIU/L during pregnancy was an independent risk factor for infantile neurodevelopment. This trial was registered at clinicaltrials.gov as NCT03710148.

Adequacy of Iodine Status and Associations with Gut Health: A Prospective Cohort Study among Infants in 8 Low- and Middle-Income Countries.

BACKGROUND: Environmental enteric dysfunction increases the likelihood of micronutrient deficiencies among infants, but few studies have assessed the potential impact of gut health on urinary iodine concentration (UIC) among this vulnerable group. OBJECTIVES: We describe the trends of iodine status among infants from 6 to 24 mo old and examine the associations between intestinal permeability, inflammation, and UIC from 6 to 15 mo of age. METHODS: Data from 1557 children enrolled in this birth cohort study conducted in 8 sites were included in these analyses. UIC was measured at 6, 15, and 24 mo of age by using the Sandell-Kolthoff technique. Gut inflammation and permeability were assessed using the concentrations of fecal neopterin (NEO), myeloperoxidase (MPO) and alpha-1-antitrypsin (AAT), and lactulose-mannitol ratio (LM). A multinomial regression analysis was used to assess the classified UIC (deficiency or excess). Linear mixed regression was used to test the effect of interactions among biomarkers on logUIC. RESULTS: All studied populations had adequate (≥100 µg/L) to excess (≥371 µg/L) median UIC at 6 mo. Between 6 and 24 mo, 5 sites displayed a significant decline in the infant's median UIC. However, median UIC remained within the optimal range. An increase of NEO and MPO concentrations by +1 unit in ln scale reduced the risk of low UIC by 0.87 (95% CI: 0.78-0.97) and 0.86 (95% CI: 0.77-0.95), respectively. AAT moderated the association between NEO and UIC (P < 0.0001). The shape of this association appears to be asymmetric and in a reverse J-shape, with a higher UIC observed at both lower NEO and AAT concentrations. CONCLUSIONS: Excess UIC was frequent at 6 mo and tended to normalize at 24 mo. Aspects of gut inflammation and increased permeability appear to reduce the prevalence of low UIC in children aged 6 to 15 mo. Programs addressing iodine-related health should consider the role of gut permeability in vulnerable individuals.

IL-9-Producing Th9 Cells Participate in the Occurrence and Development of Iodine-Induced Autoimmune Thyroiditis.

Iodine excess may cause and aggravate autoimmune thyroiditis (AIT), which is regarded as a typical kind of autoimmune disease mainly mediated by CD4+ T cells. Thus far, it is unclear whether T helper (Th) 9 cells, a novel subpopulation of CD4+ T cells, play a potential role in AIT. Therefore, in the present study, changes in Th9 cells were detected in murine models of AIT induced by excess iodine intake to explore the possible immune mechanism. Female C57BL/6 mice were divided into 7 groups (n = 8) and were supplied with water containing 0.005% sodium iodide for 0, 2, 4, 6, 8, 10, and 12 weeks. With the extension of the high-iodine intake duration, the incidence of thyroiditis and the spleen index were significantly increased, and serum thyroglobulin antibody (TgAb) titers and interleukin 9 (IL-9, major cytokine from Th9 cells) concentrations were also increased. Additionally, it was revealed that the percentages of Th9 cells in spleen mononuclear cells (SMCs) and thyroid tissues were both markedly elevated and accompanied by increased mRNA and protein expression of IL-9 and key transcription factors of Th9 cells (PU.1 and IRF-4). Significantly, dynamic changes in Th9 cells were found, with a peak at 8 weeks after high iodine intake, the time point when thyroiditis was the most serious. Importantly, Th9 cells were detected in the areas of infiltrating lymphocytes in thyroid sections. In conclusion, the continuously increasing proportions of Th9 cells may play an important role in the occurrence and development of AIT induced by high iodine intake.

Effects of Excessive Iodine on the BDNF-TrkB Signaling Pathway and Related Genes in Offspring of EAT Rats.

Excess iodine can cause autoimmune thyroiditis (AIT) in women, but it is unclear whether this has any implications for neurodevelopmental mechanisms in offspring. We studied the effects of experimental autoimmune thyroiditis (EAT) rats with different amounts of iodine intake on offspring brain development via the brain-derived neurotrophic factor (BDNF)-tropomycin receptor kinase B (TrkB) signaling pathway, because BDNF plays an important role in neurodevelopment. Rats in three thyroglobulin (Tg) immunized groups with varying iodine intakes (Tg (100 µg/L iodine), Tg + High-iodine I group (Tg + HI, 20 mg/L iodine), and Tg + High-iodine II group (Tg + HII, 200 mg/L iodine)) were injected with 800 µg Tg once every 2 weeks for 3 times. Rats in the control group (NI, 100 µg/L iodine) were immunized with saline. Arsenic-cerium catalytic spectrophotometry was used to measure urine iodine levels. The lymphocytic infiltration in the thyroids was observed by histopathological studies. Thyroid autoantibodies levels were measured using radioimmunoassay. The norepinephrine (NE) contents were measured by an enzyme-linked immunosorbent assay. The levels of the BDNF-TrkB signaling pathway and related genes were measured by quantitative real-time PCR and Western blot. Urinary iodine levels increased as iodine intake increased. Lymphocytes were significantly aggravated in Tg-immunized rats. Serum thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) levels were clearly elevated in Tg-immunized rats. Tg-immune groups had significantly lower NE levels. The BDNF-TrkB signaling pathway and related gene mRNA and protein levels were found to be significantly lower in Tg-immune groups with higher iodine levels. Maternal AIT may reduce the levels of certain neurodevelopmental mechanisms in the offspring, such as the BDNF-TrkB signaling pathway and related factors, while excessive iodine consumption by the mother may exacerbate this effect.

The effect and mechanism of excessive iodine on the endothelial function of human umbilical vein endothelial cells.

Iodine excess (IE) can cause thyroid dysfunction, thyroid diseases can adversely affect cardiovascular function. Accordingly, this study was to explore the direct and indirect effects of IE on endothelial function. Nthy-ori 3-1 and HUVECs cells were treated with potassium iodide (KI). CCK-8, LDH leakage, Elisa, RT-PCR and Western blotting were used to detect relevant indicators. Results showed that a certain level of KI can directly and indirectly reduce the viability of HUVECs and increase cytotoxicity. KI decreased the expression of ET-1 and VWF in HUVECs, inhibited the secretion of ET-1 in culture medium, and increased the expression of IL-6 and TNFα in HUVECs or Nthy-ori 3-1 cells alone. In the co-culture system, KI decreased the expression of ET-1 and THBD and increased the expression of TNFα and IL-6. Collectively, IE can directly and indirectly inhibit endothelial function of endothelial cells, which may be related to its induced inflammatory response.

Protection of Vitamin C on Oxidative Damage Caused by Long-Term Excess Iodine Exposure in Wistar Rats.

Vitamin C was reported to be able to protect against oxidative damage due to its reducibility. 120 Wistar rats were randomly divided into 4 × 2 groups, including normal iodine (NI), high iodine (HI), low vitamin C (HI + LC), and high vitamin C (HI + HC); potassium iodide (KI) and potassium iodate (KIO3) were commonly used as additives for iodized salt, so every group was also divided into KI and KIO3 groups. After 6 months' feed, the activities of antioxidant enzymes and Lipid Peroxide (MDA) content in serum, liver, kidney, brain, thyroid and lens were determined. In serum, for males, long-term excess iodine intake caused oxidative damage; in the liver, male rats in the HI + LC group had the highest MDA content, which showed that low-dose vitamin C might promote oxidative damage; in kidneys, the MDA content in the HI and HI + LC groups of females was higher; in the brain, high-dose vitamin C could increase the activity of superoxide dismutase (SOD), which was decreased by high iodine intake, and it also decreased MDA content; in the thyroid, for KIO3, the activity of SOD in the HI group was lower than NI and HI + LC; in the lens, the MDA content in females was lower than males. Long-term excess iodine exposure caused oxidative damage and showed sex difference, and vitamin C had a protective effect on it, especially for high-dose vitamin C.

Effects of maternal iodine nutritional status on neurodevelopmental and cognitive function of rat offspring.

Objectives: This study aimed to explore the effect of maternal iodine status on the brain development of offspring in rats. Since in human studies, the interference of environmental factors and other nutrients cannot be removed. Materials and methods: A total of 48 female Wistar rats were randomly divided into four groups: low iodine (LI), normal iodine (NI), 10-fold high iodine (10HI), and 50-fold high iodine (50HI). The rats were killed on the 15th day of pregnancy and lactation after collecting 24-h urine. The iodine concentration in 24-h urine, blood, and placenta of pregnant rats, and 24-h urine, milk, blood, and mammary glands of lactating rats was determined by inductively coupled plasma mass spectrometry. The thyroid hormone of pregnant and lactating rats was detected by chemiluminescence. The offspring were subjected to the Morris water maze on the 10th day after birth. Serum was collected to detect the thyroid hormone of offspring. The protein expression of neuroendocrine-specific protein (NSP)-A and brain-derived neurotrophic factor (BDNF) in the offspring brain were studied. Results: Iodine storage in the placenta during pregnancy and mammary glands during lactation was positively correlated with iodine intake, and iodine storage in the placenta and mammary glands in the 50HI group was significantly higher than that in the NI group (P = 0.045 and P = 0.040). Compared with the NI group, the offspring thyroid-stimulating hormone (TSH) level was significantly higher in the 10HI group (P = 0.046), and the FT4 level was significantly lower in the 50HI group (P = 0.032). The Morris water maze showed that LI and 50HI groups required longer time and distance to find the platform than the NI group (P < 0.001). The platform crossing numbers in the LI and 50HI groups decreased significantly (P < 0.001). The expression of NSP-A in offspring brain was lower in the 10HI and 50HI groups than in the NI group (P = 0.026 and P = 0,008). BDNF expression levels were significantly lower in the LI, 10HI, and 50HI groups than in the NI group (P < 0.001). Conclusion: Maternal iodine intake affects iodine storage in the placenta and lactating mammary gland, which in turn affects thyroid function and BDNF and NSP-A expression in the offspring.

Urinary sodium, iodine, and volume in relation to metabolic syndrome in Mesoamerican children and their parents.

BACKGROUND AND AIMS: The roles of sodium or iodine intake on the metabolic syndrome (MetS) etiology remain controversial. We evaluated the associations of 24 h urinary sodium and iodine with MetS among Mesoamerican children and their adult parents. METHODS AND RESULTS: We conducted a cross-sectional study among 217 school-age children and 478 parents from 9 Mesoamerican cities. Exposures were high 24 h urinary sodium excretion and concentration (>2000 mg/d or mg/L, respectively) and high 24 h urinary iodine excretion and concentration (≥300 µg/d or µg/L, respectively). In children, the outcome was a standardized metabolic score from five criteria analogous to the Adult Treatment Panel (ATP) III criteria. In adults, MetS was defined according to the ATP III criteria. We estimated adjusted mean differences in the metabolic risk score and adjusted prevalence ratios of MetS between exposure categories using multivariable regression. In children, high sodium concentration was associated with a 0.10 units (43% of a SD) higher score (P = 0.001) and high iodine concentration was related to a 0.09 units (39% of a SD) higher score (P = 0.009). Unexpectedly, high 24 h urinary volume was associated with a lower metabolic score. In adults, high 24 h sodium excretion was related to hypertension and high iodine concentration was related to increased MetS prevalence. CONCLUSION: High sodium and iodine concentrations, but not 24 h iodine excretion, are significantly associated with MetS in children, whereas high 24 h urinary volume is related to a decreased metabolic score. In adults, high iodine concentration tends to be related to increased MetS prevalence, but not 24 h iodine excretion.

Study on the Effect of Different Iodine Intake on Hippocampal Metabolism in Offspring Rats.

Iodine is an essential trace element in the human body. Severe maternal iodine deficiency during pregnancy leads to obvious intellectual disability in the offspring. The effects of iodine deficiency on brain development have been demonstrated, but there is no clear evidence of the effects of iodine excess on brain development. To clarify the effects of iodine excess on the brain development of offspring and to provide clues to the mechanisms underlying the effects of iodine deficiency and iodine excess on the brain development of offspring. In this study, animal models with different iodine intakes were constructed using potassium iodate (KIO3). The models included four experimental groups (low-iodine group one (LI, 0µg/L iodine), low-iodine group two (LII, 5µg/L iodine), high-iodine group one (HI, 3000µg/L iodine), and high-iodine group two (HII, 10000µg/L iodine)) and one control group (NI, 100µg/L iodine). There were 20 female rats in each group, and 8 offspring were chosen from each group following birth to assess metabolic alterations. The metabolites of subsets of brain hippocampal tissue were profiled by ultra-performance liquid chromatography-linked electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS) and the results were subjected to multivariate data analysis. Differential substances were screened by t test (p<0.05), principal component analysis (PCA), and partial least squares analysis (PLS-DA, VIP>1). The thyroid function of the female rats in the experimental group was abnormally changed. Metabolic analysis showed that the five groups were separated which revealed significant differences in hippocampal tissue metabolism among the five groups of offspring. A total of 12 potential metabolites were identified, with the majority of them being related to amino acid and energy metabolism. These metabolites are involved in various metabolic pathways, are interrelated, and may play a function in brain development. Our study highlights changes in metabolites and metabolic pathways in the brain hippocampus of offspring rats with different iodine intakes compared to controls, revealing new insights into hippocampal metabolism in offspring rats and new relevant targets.

Iodine excess induces hepatic, renal and pancreatic injury in female mice as determined by attenuated total reflection Fourier-transform infrared spectrometry.

Limited knowledge of the long-term effects of excessive iodine (EI) intake on biomolecular signatures in the liver/pancreas/kidney prompted this study. Herein, following 6 months of exposure in mice to 300, 600, 1200 or 2400 µg/L iodine, the biochemical signature of alterations to the liver/pancreas/kidney was profiled using attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy coupled with principal component analysis-linear discriminant analysis (PCA-LDA). Our research showed that serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), serum creatinine (Scr), insulin, blood glucose levels and homeostasis model assessment for insulin resistance (HOMA-IR) index in the 1200 and 2400 µg/L iodine-treated groups were significantly increased compared with those in the control group. Moreover, histological analysis showed that the liver/kidney/pancreas tissues of mice exposed to EI treatment displayed substantial morphological abnormalities, such as a loss of hepatic architecture, glomerular cell vacuolation and pancreatic neutrophilic infiltration. Notably, EI treatment caused distinct biochemical signature segregation between EI-exposed versus the control liver/pancreas/kidney. The main biochemical alterations between EI-exposed and control groups were observed for protein phosphorylation, protein secondary structures and lipids. The ratios of amide I-to-amide II (1674 cm-1 /1570 cm-1 ), α-helix-to-ß-sheet (1657 cm-1 /1635 cm-1 ), glycogen-to-phosphate (1030 cm-1 /1086 cm-1 ) and the peptide aggregation (1 630 cm-1 /1650 cm-1 ) level of EI-treated groups significantly differed from the control group. Our study demonstrated that EI induced hepatic, renal and pancreatic injury by disturbing the structure, metabolism and function of the cell membrane. This finding provides the new method and implication for human health assessment regarding long-term EI intake.

The Effects of Long-Term High Water Iodine Levels in the External Environment on the Carotid Artery.

Iodine excess typically affects thyroid function in the human body and may damage carotid artery. Four investigation plots with different water iodine levels were selected in Shandong Province, China. These included a low, medium, and high iodine group and an iodine excess group whose water iodine content was < 10, 50-150, 150-300, and > 300 µg/L, respectively. Residents aged 20-65 years answered a questionnaire and underwent carotid artery ultrasonography, and their height, weight, and urinary iodine concentrations were measured. A total of 2026 individuals participated in the study. Urinary iodine concentration increased with increased water iodine levels. The medial thickening rate and intimal roughness rate in the iodine excess group were significantly higher than in the other three groups. After controlling for factors such as gender, age, and BMI, iodine excess remained as a risk factor for carotid intima-media thickening. Excess water iodine in the external environment is a risk factor for intima-media thickening of the carotid artery, suggesting that iodine excess may cause vascular injury and promote atherosclerosis.

The Impact of Iodine Exposure in Excess on Hormonal Aspects and Hemato-Biochemical Profile in Rats.

Excessive exposure of iodine over a time is well known to cause thyroid dysfunction, which may be followed by different effects on body organs. The present study aimed to illustrate the impacts of exposure of rats to excess iodine (above the tolerable range) and the reversibility of any negative impacts on hormonal profile related to thyroid besides cortisol and the hematological and biochemical parameters along with the histopathological alterations in the thyroid gland, liver, kidneys, and heart. Seventy-five rats were divided equally into three groups: Group 1 was control animals. Groups 2 and 3 received sodium iodide (NaI) orally at a dose of (35 and 70 mg/kg BW), which corresponded to (500 and 1000) times excess iodine from the physiological dose, respectively for 30 days, then the NaI administration stopped in the treated groups for 15 consecutive days. Blood and tissue samples were collected twice for various experimental tests after 30 and 15 days of exposure to excess iodine and stopping the exposure, respectively. Overall results revealed that excess iodine in both tested groups developed a hyperthyroid condition, hypercortisolism, relative polycythemia, neutropenia, elevation in serum liver and cardiac enzymes activities, hyperprotenemia, hyperglobulinemia, elevation in serum urea, and cardiac troponin I concentrations (p < 0.05). It was concluded that the excess iodine caused hyperthyroidism, which was associated with significant changes in erythrogram and leukogram and alterations in hepatic, renal, and cardiac functions in an iodine dose-dependent damage relationship and the most of negative impacts continued after stopping the administration.

A Meta-Analysis of the Effect of Iodine Excess on the Intellectual Development of Children in Areas with High Iodine Levels in their Drinking Water.

The purpose of this meta-analysis is to comprehensively investigate the effect of iodine excess on children's intellectual development in areas with high iodine levels in their drinking water. We systematically searched the electronic databases and identified 17 publications (16 in Chinese and 1 in English) on the effect of iodine excess on children's intelligence published between January 31, 1985, and January 31, 2020. This meta-analysis included 14,794 children from 28 studies. The results showed that compared with the control group, the intelligence level of children in the high iodine group reduced significantly by 1.64 points (WMD=-1.64; 95% CI (-3.225, -0.049), Z=2.02, P<0.05). Subgroup analyses were performed according to the water iodine concentration, water iodine concentration of the control group, the intelligence test method, and regions of China (i.e., north and south). We noted that when the water iodine concentration was <300µg/L, 301-600µg/L, 600.1-900µg/L, and >900µg/L, the intelligence level of the high iodine groups decreased by varying degrees, although not statistically significant (all P>0.05). The water iodine concentration of the control group was divided into two groups (<150 µg/L and <100 µg/L) and the heterogeneity analysis showed that the heterogeneity of the control group decreased significantly when the concentration of water iodine was <150 µg/L, I2 = 67.3%, P<0.001, which indicated a potential source of heterogeneity. The analyses by test method showed that among the studies which used the China Joint Raven's test, the intelligence level of children in the high iodine group was 0.86 points lower than in the control group (P>0.05). Conversely, we observed that among the studies which used the China Binet intelligence test and the binaphthalene intelligence test of Tanzhida in Japan to evaluate children's intelligence level, the intelligence level of children in the high iodine groups was significantly lower (3.65 points and 8.0 points, respectively) compared with the control groups (P<0.05). The analysis of the regions of China demonstrated that whereas the reduction in children's intelligence level from excess iodine in the north of China was not statistically significant (WMD=-0.16, 95% CI (-2.18, 1.85), P>0.05), the association was statistically significant in the southern part of China (WMD=-1.86, 95% CI (-3.57, -0.09), P<0.05). This study found that high iodine concentration was statistically significantly associated with a decline in intelligence level in children. Comparatively, the intelligence level of children who were exposed to high iodine concentrations reduced significantly by 1.64 points. These findings have public health implications.