Thyroid Damage Research Articles

Active Vitamin D Ameliorates Arsenite-Induced Thyroid Dysfunction in Sprague–Dawley Rats by Inhibiting the Toll-like Receptor 4/NF-KappaB-Mediated Inflammatory Response

Arsenic, a well-known environmental endocrine disruptor, exerts interference on the body’s endocrine system. Our previous investigations have demonstrated that chronic exposure to sodium arsenite (NaAsO2) can induce thyroid damage and dysfunction in Sprague–Dawley (SD) rats. Vitamin D (VD) is an indispensable fat-soluble vitamin that plays a crucial role in maintaining thyroid health. In recent years, numerous studies have demonstrated the association between VD deficiency and the development of various thyroid disorders. However, the precise intervention roles and mechanisms of VD in arsenic-induced thyroid injury remain elusive. This study aimed to investigate the intervention effect of VD on NaAsO2-induced thyroid dysfunction in SD rats. The results demonstrated that exposure to NaAsO2 activates the TLR4/NF-κB signaling pathway in thyroid tissue of rats, leading to apoptosis of thyroid cells and subsequent inflammatory damage and disruption of serum thyroid hormone secretion. Supplementation with TAK-242 (a TLR4 inhibitor) and VD effectively inhibits the activation of the TLR4/NF-κB signaling pathway in rat thyroid tissue exposed to NaAsO2, thereby reducing the inflammatory damage and dysfunction caused by arsenic exposure. In conclusion, the findings of this study offer innovative insights into the application of VD in the prevention and treatment of thyroid dysfunction caused by arsenic exposure.

Molecular disturbances and thyroid gland dysfunction in rats chronically exposed to a high dose of NaAsO₂: Insights from proteomic and phosphoproteomic analyses

Arsenic is a ubiquitous hazardous metalloid that poses a significant threat to human health. Although researchers have investigated the detrimental effects of arsenic on the thyroid, a comprehensive exploration of its toxicological impact and underlying molecular mechanisms remains to be conducted. Both this study and our previous reports demonstrated that chronic exposure to sodium arsenite (NaAsO2) results in histological impairment and dysfunction of the thyroid glands in Sprague-Dawley (SD) rats. Proteomic and phosphoproteomic analyses were performed to investigate the molecular mechanisms underlying the effects of chronic NaAsO2 exposure on thyroid function in SD rats. NaAsO2 disrupts the synthesis of thyroid hormones (THs) and alters the expression of the THs-synthesizing enzyme dual oxidase 2. In addition, oxidative phosphorylation, the AMP-activated protein kinase signaling pathway, central carbon metabolism in cancer, cysteine and methionine metabolism, cellular response to heat stress, and protein processing in the endoplasmic reticulum were upregulated, whereas glutathione metabolism was downregulated. In conclusion, this study revealed thyroid damage in SD rats induced by chronic NaAsO2 exposure and elucidated the disrupted molecular pathways, thereby providing novel insights into the molecular mechanisms underlying arsenic exposure and its impact on thyroid function.

Lactoferrin alleviates oxidative stress and endoplasmic reticulum stress induced by autoimmune thyroiditis by modulating the mTOR pathway in the thyroid.

Autoimmune thyroiditis (AITD) is a prevalent autoimmune disorder characterized by the immune system's attack on thyroid tissue, potentially leading to thyroid dysfunction, with a current lack of effective treatment modalities. Lactoferrin, a crucial functional dietary component obtainable from food sources, primarily exists in mammalian milk. We aim to investigate whether dietary supplementation with lactoferrin can protect the thyroid in Experimental Autoimmune Thyroiditis (EAT) rats. Our study reveals significantly elevated levels of oxidative stress (OS) and endoplasmic reticulum stress (ERS) in the AITD. Lactoferrin markedly reduces OS and infiltration of inflammatory cells in the thyroid tissue of EAT rats. Furthermore, lactoferrin inhibits ERS levels in the thyroid of EAT rats and alleviates cellular apoptosis. In vivo and in vitro experiments elucidate that its protective effect is primarily achieved through the inhibition of mTOR signaling pathway activation. In summary, lactoferrin, a nutrient readily obtainable from food sources, appears to be effective in mitigating thyroid damage in AITD.

Hypothyroidism Induced by a TSH Receptor Peptide-Implications for Thyroid Autoimmunity.

Background: The "neutral" thyrotropin receptor autoantibodies (N-TSHR-Ab) directed at the TSHR ectodomain's hinge region have been shown to induce thyroid cell damage in vitro. During these earlier studies, we developed a mouse monoclonal antibody (MC1) specific for a peptide (amino acid 322-340) in the region (MC1-Mab) which was able to induce thyroid cell stress and apoptosis when administered invivo. Methods: In order to examine the effect of invivo generated N-TSHR-Abs, rather than an acutely administered monoclonal antibody, we immunized Balb/c mice with the hinge region peptide over 18 weeks. Serum TSHR antibodies, specific TSHR hinge region antibodies, serum thyroglobulin (TG) and anti-TG as well as thyroxine and thyrotropin (TSH) levels were examined to evaluate the response to the immunization. Histological examination of the thyroid glands and flow cytometry of spleen T cells, B cells and macrophages were also performed to explore the underlying mechanisms. Results: We found that TSHR-peptide immunized mice developed N-TSHR-Abs against the peptide which resulted in thyroid damage shown by thyroid follicular destruction with follicular cell apoptosis, M1 macrophage infiltration, thyroglobulin release, and induction of thyroglobulin antibodies. This resulted in hypothyroidism with increased TSH levels. Conclusion: This study demonstrated that endogenous neutral antibodies to the TSHR could induce thyroid cell damage from apoptosis and M1 macrophage infiltration and resulted in hypothyroidism.

Papillary microcarcinoma in three generations of the first degree relatives

Family papillary microcarcinoma of the thyroid gland is observed in 3–10 % of patients with cancer from follicular epithelial cells. Diagnosis and treatment are controversial. Three patients from the same family of the first degree of kinship were operated for family papillary microcarcinoma of the thyroid gland in Voronezh Regional Clinical Hospital No. 1. Only the first patient complained of the neck deformity, her son and granddaughter had an asymptomatic course of the disease. Metastases to the lymph nodes of the neck and bilateral localization of the tumor were not revealed. In the third generation, multifocal tumor growth was diagnosed at the age of 19. All patients underwent thyroidectomy. In the first patient, the period of relapse–free follow-up after surgery was 18 years, in the second and third – 5 years. In the family form of papillary thyroid carcinoma, we consider active screening of relatives justified since the disease in the new generation may develop at a younger age and with the risk of multifocal thyroid damage even in microcarcinomas.

Radiation protection in dental imaging: Evaluating the impact of the SABA thyroid shield during panoramic and cone beam computed tomography

BackgroundDental panoramic radiography (DPR) and cone beam computed tomography (CBCT) are an imaging modalities in dentistry. However, these procedures involve exposure to ionising radiation, raising concerns about radiation-induced thyroid damage. To mitigate these risks, thyroid shields have been introduced. This study aimed to evaluate the effectiveness of the SABA thyroid shield in reducing thyroid radiation exposure during DPR and CBCT scans. MethodAn experimental study to measure surface dose in the thyroid region during (DPR) and (CBCT) scans using an Anthropomorphic Phantom and a Solid-State Detector. The attenuation percentage was calculated between radiation surface doses with and without shielding. The significance of the Saba thyroid shield was calculated using a t-test. ResultsFor DPR scans, the average surface doses in the thyroid reduced significantly from 301.1 μGy (at 85 kVp) and 170.3 μGy (at 60 kVp) to 64.43 μGy and 12.94 μGy, respectively, when the Saba thyroid shield was used. For CBCT scans, the average surface doses in the thyroid decreased significantly from 814.43 μGy (for 11 × 13 cm2 field size) and 32.40 μGy (for 5 × 5 cm2 field size) to 62.91 μGy and 12.07 μGy, respectively, with the application of the Saba thyroid shield. The maximum attenuation percentages in the thyroid for the DPR and CBCT scans were 92.40% and 92.27%, respectively. Statistically significant differences between the surface dose reduction with the Saba shield and without it was observed in both DPR scans (p < 0.0000) and CBCT scans (p < 0.0003). ConclusionThe study demonstrates that Saba thyroid shields effectively reduce doses in the thyroid region during dental DPR and CBCT scans. The dose reduction depends on tube voltage for DPR scans, field size, and its position for CBCT scans. Findings highlight the importance of using Saba thyroid shields to minimise radiation exposure and protect the thyroid gland during dental scans.

Indole-3-Butyric Acid, a Natural Auxin, Protects against Fenton Reaction-Induced Oxidative Damage in Porcine Thyroid.

We present results on the potential protective antioxidant properties of indole-3-butyric acid. Indole-3-butyric acid is an indole derivative defined as an auxin and widely known as a plant growth regulator. It naturally occurs in Arabidopsis thaliana, which is applied as a model plant in genetic studies. Oxidative damage to membrane lipids (lipid peroxidation; LPO) in porcine thyroid homogenates was induced by Fenton reaction substrates (Fe2+ + H2O2). Iron (Fe2+) was used in very high concentrations of 1200, 600, 300, 150, 75, 37.5, 18.75, 9.375, 4.687, and 2.343 µM. Indole-3-butyric acid (10.0, 5.0, 2.5, 1.25, and 0.625 mM) was applied to check whether it prevents the above process. The LPO level, expressed as malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) concentration, was measured spectrophotometrically. Expectedly, Fenton reaction substrates, in a Fe2+ concentration-dependent manner, increased LPO level, with the lowest effective concentration of iron being 9.375 µM. In the case of almost all concentrations of indole-3-butyric acid, this auxin has exhibited very promising antioxidant protection, with the most effective concentrations being 10.0 and 5.0 mM; however, as low concentrations of indole-3-butyric acid at 1.25 mM was still effective. Indole-3-butyric acid used alone did not change the basal level of LPO, which is a favourable effect. To summarise, indole-3-butyric acid has protective antioxidant properties against experimentally induced oxidative damage to membrane lipids in the thyroid, and this is for the first time documented in the literature. This compound can be considered a natural protective agent present in plants, which can serve as a dietary nutrient.

Exploring the molecular mechanisms underlying radiation-induced thyroid damage using an organoid model

Exploring the molecular mechanisms underlying radiation-induced thyroid damage using an organoid model

Polychlorinated Biphenyls (PCBS)-induced oxidative stress and inflammation in human thyrocytes: involvement of AhR and NRF-2/HO-1 pathway.

In this in vitro study, we investigated the effects of polychlorinated biphenyls (PCBs) on human thyrocytes, with a focus on the involvement of AhR, a key player in xenobiotic response, and the anti-oxidant Nrf-2/HO-1 pathway. Primary cultured thyrocytes were exposed to the dioxin-like congeners PCB118 and PCB126 at 2.5 and 5 µM concentrations. mRNA expression was assessed by real-time PCR, and protein expression by Western Blot and ELISA, while protein quantification was assessed by densitometric analysis. In cultured thyrocytes, PCB118 and PCB126 induced a significant (P < 0.01) increase of mRNA and protein levels of the pro-inflammatory cytokines IL-1beta and IL-6, while reducing those of thyroglobulin (TG) and NIS (p < 0.05), indicating down-regulation of these thyroid-specific genes in PCB-induced inflammation. ROS production also increased (p < 0.001). mRNA levels of AhR and the downstream molecules cytochrome P4501A, Nrf-2/HO-1 increased (p < 0.001), as well as related protein levels (p < 0.01), suggesting the activation of AhR and Nrf-2 pathways in response to PCBs exposure. AhR silencing decreased AhR-related gene expression and restored NIS and TG expression, while reducing inflammatory cytokines and oxidative stress markers (p < 0.05). Dioxin-like PCBs (PCB118 and PCB126) may promote inflammation and oxidative stress in thyrocytes, impairing the expression of genes that are key players of thyroid function. These effects can be partially attributed to the activation of the AhR and Nrf-2 pathways. These data may contribute to explain the mechanisms underlying thyroid toxicity of PCBs, highlighting the potential role of these pollutants as a trigger of autoimmune thyroid inflammation and damage.

Combined transcriptome and microbiome analysis reveals the thyrotoxic effects of PM2.5 in female rats

Pervasive environmental pollutants, specifically particulate matter (PM2.5), possess the potential to disrupt homeostasis of female thyroid hormone (TH). However, the precise mechanism underlying this effect remains unclear. In this study, we established a model of PM2.5-induced thyroid damage in female rats through intratracheal instillation and employed histopathological and molecular biological methods to observe the toxic effects of PM2.5 on the thyroid gland. Transcriptome gene analysis and 16S rRNA sequencing were utilized to investigate the impact of PM2.5 exposure on the female rat thyroid gland. Furthermore, based on the PM2.5-induced toxic model in female rats, we evaluated its effects on intestinal microbiota, TH levels, and indicators of thyroid function. The findings revealed that PM2.5 exposure induced histopathological damage to thyroid tissue by disrupting thyroid hormone levels (total T3 [TT3], (P < 0.05); total T4 [TT4], (P < 0.05); and thyrotropin hormone [TSH], (P < 0.05)) and functional indices (urine iodine [UI], P > 0.05), thus further inducing histopathological injuries. Transcriptome analysis identified differentially expressed genes (DEGs), primarily concentrated in interleukin 17 (IL-17), forkhead box O (FOXO), and other signaling pathways. Furthermore, exposure to PM2.5 altered the composition and abundance of intestinal microbes. Transcriptome and microbiome analyses demonstrated a correlation between the DEGs within these pathways and the flora present in the intestines. Moreover, 16 S rRNA gene sequencing analysis or DEGs combined with thyroid function analysis revealed that exposure to PM2.5 significantly induced thyroid hormone imbalance. We further identified key DEGs involved in thyroid function-relevant pathways, which were validated using molecular biology methods for clinical applications. In conclusion, the homeostasis of the "gut-thyroid" axis may serve as the underlying mechanism for PM2.5-induced thyrotoxicity in female rats.

Mechanism underlying the role of integrin α3β1 in adhesive dysfunction between thyroid cells induced by diesel engine exhaust particles

The role and mechanisms of DEP exposure on thyroid injury are not yet clear. This study explores thyroid damage induced by in vivo DEP exposure using a mouse model. This study has observed alterations in thyroid follicular architecture, including rupture, colloid overflow, and the formation of voids. Additionally, there was a significant decrease in the expression levels of proteins involved in thyroid hormone synthesis, such as thyroid peroxidase and thyroglobulin, their trend of change is consistent with the damage to the thyroid structure. Serum levels of triiodothyronine and tetraiodothyronine were raise. However, the decrease in TSH expression suggests that the function of the HPT axis is unaffected. To delve deeper into the intrinsic mechanisms of thyroid injury, we performed KEGG pathway enrichment analysis, which revealed notable alterations in the cell adhesion signaling pathway. Our immunofluorescence results show that DEP exposure impairs thyroid adhesion, and integrin α3β1 plays an important role. CD151 binds to α3β1, promoting multimolecular complex formation and activating adhesion-dependent small GTPases. Our in vitro model has confirmed the pivotal role of integrin α3β1 in thyroid cell adhesion, which may be mediated by the CD151/α3β1/Rac1 pathway. In summary, exposure to DEP disrupts the structure and function of the thyroid, a process that likely involves the regulation of cell adhesion through the CD151/α3β1/Rac1 pathway, leading to glandular damage.

Autoimmune Thyroiditis in Patients With Diabetes Mellitus: Retrospective Study of 91 Cases.

Background Detection and quantification of anti-thyroid antibodies make it possible to confirm the diagnosis of thyroid dysfunction as well as its autoimmune origin and monitor thyroid damage in diabetic patients. The aim of this study is to determinethe seroprevalence of anti-thyroid antibodies in hospitalized diabetic patients. Materials and methods This retrospective study focused on 91 diabetic patients hospitalized in the endocrinology department of Ibn Sina Hospital, Rabat, Morocco, between January 1 and December 31, 2022. The study population was divided into two groups: 19 patients with type 1 diabetes (13 females and six males, with an age range of 20-70 years) and 72 patients with type 2 diabetes (52 females and 20 males, with an age range of 40-71 years). Hemoglobin (HbA1c) levels were determined with high-performance liquid chromatography (Hb-HPLC) analyzer from blood samples collected in EDTA tubes, and anti-thyroid antibodies (anti-TPO and/or anti-TG) were measured by chemiluminescent microparticle immunoassays (CMIA) in human serum using the ALINITY analyzer. Results Among type 1 diabetic patients, 42.1% (n = 8)were positive for anti-TPO and anti-TG antibodies, while 31.5% (n = 6)were positive only for anti-TPO antibodies. Among type 2 diabetic patients, 15.2% (n = 11) were positive only for anti-TPO antibodies, while 20.8% (n = 15) were positive for anti-TPO and/or anti-TG antibodies. The prevalence of anti-thyroid antibodies was higher in females, consistent with other studies. This could be linked to the involvement of autoimmune processes in the development of thyroid dysfunction in type 2 diabetics. Conclusions Testing for anti-thyroid antibodies in diabetic patients and their relatives helps detect subclinical conditions, which could later manifest as biological and clinical deficiencies, guiding monitoring parameters.

Immune checkpoint inhibitors-related endocrinopathies exhibit increased severity in breast cancer patients: a real-world study.

This study aims to systematically evaluate the incidence of immune checkpoint inhibitors (ICIs)-related endocrinopathies and their onset time in patients with breast cancer (BC) in a real-world setting. An analysis was conducted on the medical records of 122 BC patients who underwent ICIs therapy at the Department of Breast Surgery, Guangdong Provincial People's Hospital, from April 2019 to September 2021. Follow-up data continued until October 2022. The research indicated that 60.66% of BC patients experienced ICI-related endocrinopathies. The endocrinopathies included pituitary injury (7.38%), primary thyroid dysfunction (34.43%), supranormal fasting blood glucose or glycohemoglobin levels (16.39%), and adrenal injury (2.46%). Subgroup analyses were further performed based on clinical characteristics, demonstrated variability in the incidence of ICI-related endocrinopathies. Notably, subpopulations harboring genetic mutations exhibited a markedly higher prevalence of hypophysitis, as evidenced by a statistically significant association (P = 0.022). Similarly, individuals with HER2 positivity were found to have a significantly increased incidence of pancreatic islet injury (P = 0.023). Moreover, the study documented that the median onset times of ICIs-related endocrinopathies in pituitary, thyroid, pancreatic, and adrenal damage were 264, 184, 99 and 141 days, respectively, which were substantially longer compared to previous reports involving other tumors. Remarkably, even after 500 days of initiating ICI therapy, new cases of ICI-related endocrine disorders continue to emerge, suggesting a situation of delayed onset of ICI-related endocrinopathies in BC patients. The retrospective analysis confirmed a higher incidence and longer median onset time of ICI-related endocrinopathies in BC patients compared to other cancers. These outcomes underscore the critical need for regular and extended monitoring of endocrine functions in BC patients receiving ICI therapy, advocating for personalized monitoring approaches based on individual clinical profiles.

Mechanism of Prunella vulgaris L. and luteolin in restoring Tfh/Tfr balance and alleviating oxidative stress in Graves' disease

BackgroundThe pathophysiology of Graves' disease (GD) involves imbalances between follicular helper T (Tfh) and follicular regulatory T (Tfr) cells, as well as oxidative stress (OS). Prunella vulgaris L. (Xia Ku Cao, XKC) and its primary bioactive compound, luteolin, are recognized for their potential in treating GD. Yet, the mechanism accounting for the immune-modulatory and antioxidant effects of XKC remains elusive. PurposeThis study aims to evaluate the pharmacological effects and elucidate the underlying mechanism of XKC and luteolin in a GD mouse model induced by recombinant adenovirus of TSH receptor A subunit (Ad-hTSHR-289). MethodsHigh-Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry (HPLC-QTOF MS) was used to detect the constituents of XKC. The GD model was established through inducing female BALB/c mice with three intramuscular injections of Ad-TSHR-289. Thyroid function, autoantibody and OS parameters were measured by ELISA. Changes of Tfh cells and Tfr cells were detected by flow cytometry. RT-qPCR, Western Blotting, immunohistochemistry were used to explore the related molecular mechanisms. ResultsA total of 37 chemical components from XKC were identified by HPLC-QTOF MS, represented by flavonoids, steroids, terpenoids, and luteolin. XKC and luteolin reduced T4, TRAb levels and facilitated the recovery from thyroid damage in GD mice. Meanwhile, XKC and luteolin effectively alleviated OS by decreasing the levels of MDA, NOX2, 4-HNE, 8-OHdG, while increasing GSH level. Flow cytometry showed that XKC and luteolin restored the abnormal proportions of Tfh/Tfr and Tfh/Treg, and the mRNA levels of IL-21, Bcl-6 and Foxp3 in GD mice. In addition, XKC and luteolin inhibited PI3K, Akt, p-PI3K and p-Akt, but activated Nrf2 and HO-1. ConclusionXKC and luteolin could inhibit the development of GD in vivo by rebalancing Tfh/Tfr cells and alleviating OS. This therapeutic mechanism may involve the Nrf2/HO-1 and PI3K/Akt signaling pathways. Luteolin is the main efficacy material basis of XKC in countering GD. For the first time, we revealed the mechanism of XKC and luteolin in the treatment of GD from the perspective of autoimmune and OS.

Thyroiditis and COVID-19: focus on pediatric age. A narrative review.

In light of the growing concern over the possible link between SARS-CoV2 infection and autoimmune diseases, we conducted a review to investigate the impact of the pandemic outbreak on thyroid diseases. We carried out a narrative review of all pediatric cases described in the literature, mainly focusing on the possible association of COVID-19 with the incidence of autoimmune and post-infective thyroid diseases (namely Hashimoto's Thyroiditis (HT), Grave's Disease (GD) and Sub-Acute Thyroiditis (SAT)). We also felt it was necessary to provide a brief review of Non-thyroidal Illness Syndrome (NTIS) and Multisystem Inflammatory Syndrome in Children (MIS-C) because of their overlap with thyroiditis. There is currently no conclusive evidence linking SARS-CoV-2 infection with an increased incidence of autoimmune thyroiditis (AT) in pediatric age. However, SAT may be a mild complication of SARS-CoV-2 infection, as is the case with other viral infections. SAT typically resolves on its own and does not require treatment. NTIS may be associated with inflammatory complications, such as MIS-C, and admission to intensive care. It may also be considered a prognostic risk factor for severe disease. The hypothesized pathogenetic mechanisms of thyroid damage in COVID-19 include direct damage due to the significant expression of angiotensin-converting enzyme 2 (ACE2) in the thyroid gland, which is a ligand for the virus, and indirect damage due to immune dysregulation, such as the overproduction of IL-6, which is thought to be part of the pathogenesis of thyroiditis. However, due to the limited evidence available, further prospective longitudinal studies are required to clarify the relationship between COVID-19 and thyroid disease in children and adolescents, as well as to investigate any potential long-term consequences.

Prospective role of lusianthridin in attenuating cadmium-induced functional and cellular damage in rat thyroid

The thyroid represents the most prevalent form of head and neck and endocrine cancer. The present investigation demonstrates the anticancer effects of Lusianthridin against cadmium (Cd)-induced thyroid cancer in rats. Swiss Wistar rats were utilized in this experimental study. Cd was employed to induce thyroid cancer, and the rats were divided into different groups, receiving oral administration of Lusianthridin (20 mg/kg) for 14 days. Thyroid parameters, deiodinase levels, hepatic parameters, lipid parameters, and antioxidant parameters were respectively estimated. The mRNA expression was assessed using real-time reverse transcriptase polymerase chain reaction (RT-PCR). Lusianthridin significantly (P < 0.001) improved protein levels, T4, T3, free iodine in urine, and suppressed the level of TSH. Lusianthridin significantly (P < 0.001) enhanced the levels of FT3, FT4, and decreased the level of rT3. Lusianthridin significantly (P < 0.001) reduced the levels of D1, D2, D3, and enhanced the levels of hepatic parameters like AST, ALT. Lusianthridin remarkably (P < 0.001) altered the levels of lipid parameters such as LDL, total cholesterol, HDL, and triglycerides; antioxidant parameters viz., MDA, GSH, CAT, and SOD. Lusianthridin significantly altered the mRNA expression of Bcl-2, Bax, MEK1, ERK1, ERK2, p-eIf2α, GRP78, eIf2α, and GRP94. The results clearly state that Lusianthridin exhibits protective effects against thyroid cancer.

The priority of mesenchymal stem cells treated with melatonin in ameliorating thyroid impairment induced by amiodarone. Thorough look on the apoptotic pathway

Amiodarone treatment has been associated with thyroid alterations. This work was planned to consider therapeutic outcome of MSCs versus MSCs treated with melatonin in minimizing amiodarone –induced deviations in thyroid.We handed-down 50 male Wistar rats, then distributed them into 5 groups; I, II, III, IV, V; control, sham control, amiodarone treated, amiodarone and MSCs treated, and amiodarone, MSCs and melatonin treated groups respectively. Light microscopic examination; levels of T3, T4 and TSH, Oxidative/antioxidative tissue markers, immune-histochemical staining (Bcl2, BAX, iNOS) and real time PCR (IL-6 and VEGF and Caspase 3) were done. Results of group III showed degenerated follicles, decreased follicular cell count and diminished colloid. Some of the follicles were dilated with signs of inflammatory response and apoptosis. Increased collagen deposition in group III was marked. The positive immune-reactive cells of Bcl-2 was decreased and that of BAX and iNOS was increased, also T3 and T4 levels were significantly decreased, but TSH was significantly increased in group III comparing it to the group I. There were highly significant diminution in both SOD and GPx and upsurge in MDA intensities in groups III, IV when correlated to the control. In group IV and V the aforementioned values were restored. The PCR results showed significant increase in IL-6 and VEGF and Caspase 3 in group III compared to the control one, whereas, their values in groups IV and V were reestablished. It is concluded that stem cells can to a great extent ameliorate the thyroid damage induced by amiodarone.But, Adding melatonin to the stem cells culture was found to have auxiliary beneficial effect in the improving the thyroid structure and function.

Evaluation of Caspase-8 Level in Serum of Patients with Autoimmune Thyroid Disorders

Autoimmune thyroid diseases (AITDs), including Graves' disease and Hashimoto's thyroiditis, are characterized by lymphocytic infiltration of the thyroid and the production of thyroid autoantibodies. While the etiology of AITDs is still not fully understood, a combination of genetic susceptibility and environmental triggers is believed to contribute to the breakdown in immune tolerance. This study aimed to evaluate the levels of thyroid hormones (T3, T4, TSH), Anti-thyroid peroxidase Abs (Anti-TPO Abs), Anti-Thyroglobulin Abs (Anti-TG(, and apoptosis marker (Caspase-8 ) in Iraqi patients with AITDs compared to healthy controls. A total of 1000 patients participated in the study 820 were excluded from the study because it was non-immune thyroid disease, and 180 subjects were recruited, including 60 Graves’ disease patients, 60 HT patients, and 60 healthy controls. Serum levels of T3, T4, TSH, Anti-TPO Abs and Anti-TG, caspase 8, and inhibin were measured. T3 and T4 levels were significantly decreased in Hashimoto's thyroiditis patients and increased in Graves’ disease patients compared to controls. TSH was significantly elevated in Hashimoto's thyroiditis and reduced in Graves’ disease patients. Caspase-8 was significantly higher in Hashimoto's groups compared with the control group, and Significantly lower in Graves group compared with the control group. In conclusion, an altered balance in thyroid hormones, Anti-TPO Abs, Anti-TG, and apoptosis markers occurs in AITDs. Elevated caspase-8 suggests that increased apoptosis may contribute to thyroid damage in AITDs. Further research is needed to clarify the roles of these mediators in AITD pathogenesis.

IL-10-TG/TPO-T4 axis, the target of bis (2-ethylhexyl) tetrabromophthalate on thyroid function imbalance

Bis (2-ethylhexyl) tetrabromophthalate (TBPH) is a new type of brominated flame retardant. Some studies suggest that TBPH exposure may be associated with thyroid damage. However, there is a paucity of research on the authentic exposure-related effects and molecular mechanisms in animals or cells. In this study, we used male Sprague-Dawley (SD) rats and the Nthy ori3–1 cell line (the human thyroid follicular epithelial cell) to explore the potential effects of TBPH (5, 50, 500 mg/kg and 1, 10, 100 nM) on the thyroid. The genes and their proteins of cytokines and thyroid-specific proteins, thyroglobulin (TG), thyroid peroxidase (TPO), and sodium iodide cotransporter (NIS) were examined to investigate the possible mechanisms. At the end of the experiment, it was found that 50 and 500 mg/kg TBPH could increase the levels of total thyroxine (TT4) and free thyroxine (FT4) significantly. The messenger RNAs (mRNAs) of Tg, Tpo, Interleukin-6 (Il6), and Interleukin-10 (Il10) in the thyroid tissues from the rats treated with 500 mg/kg were enhanced clearly. Meanwhile, the mRNAs of TG, TPO, IL6, and IL10 were elevated in Nthy ori3–1 cells treated with 100 nM TBPH as well. The mRNAs of TG and TPO were elevated after the knockdown of IL6. To our surprise, after the knockdown of IL10 or the treatment of anti-IL-10-receptor (anti-IL-10-R) antibody, the mRNAs of TG and TPO were significantly reduced, and the effects of TBPH were diminished. In conclusion, our results suggested that the IL-10-IL-10R-TG/TPO-T4 axis is one important target of TBPH in the thyroid.

Grading of Hashimoto’s thyroiditis in cytology and its association with ultrasonographic and biochemical parameters

Introduction and Aim: In the post-iodization period, Hashimoto's thyroiditis (HT) is most likely the most prevalent cause of goitre and hypothyroidism, particularly in women of reproductive years. This study was undertaken to grade HT on Fine Needle Aspiration Cytology smears and determine their usefulness in predicting thyroid damage in association with clinical history, radiological and biochemical findings. Materials and Methods: Total of 151 cases were diagnosed cytologically in duration of over 2 years as Hashimoto’s thyroiditis/lymphocytic thyroiditis. Cytology scoring technique was used to analyse smears and were correlated with radiological, biochemical findings and were evaluated statistically by ANOVA and Kruskal Wallis tests. Results: In the current study, the most frequent group of individuals with Hashimoto's thyroiditis were between the ages of 40 and 50. Females (145 cases, 96%) were commonly affected and the commonest presentation was a diffuse (125 cases ,82.8%) thyroid enlargement. Cytological grading of Hashimoto’s thyroiditis were as follows,54 (35.8%) patients were Grade I, 81(53.6%) patients were Grade II thyroiditis and 16 (10.6%) patients were Grade III thyroiditis. Biochemically, 78 (56.5%) of the cases were hypothyroid, 51 (37%), euthyroid, and 9 (6.5%) were hyperthyroid. Ultrasonography revealed 76 (50.3%) patients with hypoechoic micronodules, 71 (47%) with echogenic septae, 101 (66.9%) with increased vascularity, and 6 (4%) with normal findings. The grades of lymphocytic thyroiditis and the biochemical data were found to be statistically significant (p=0.001). Furthermore, there was a strong correlation between the grades and specific ultrasound findings, such as echogenic septae (p=0.042) and diffuse hypoechogenicity (p=0.046). Conclusion: Cytological scoring system in Hashimoto’s thyroiditis can predict thyroid functional status and aid in determining the severity of the disease.