ABSTRACT
Atrazine is a widely applied herbicide to improve crop yield and maintain general health. It has been reported to impair thyroid function and architecture in experimental animals. Alterations in thyroid hormones disrupt normal body function and metabolism. Silymarin, a hepatoprotective flavonolignan, was found to improve thyroid function and body metabolism. Additionally, garlic displays several protective effects on body organs. Therefore, this study explored the prophylactic impact of natural compounds comprising silymarin and garlic extract on disrupted thyroid function, hepatic iodothyronine deiodinase type 1, and metabolic parameters in atrazine-intoxicated male rats. We found that daily pre- and co-treatment of atrazine-intoxicated male rats with silymarin (100 mg/kg, p.o) and/or garlic extract (10 mg/kg, p.o) significantly improved thyroid activation and hepatic functionality as evidenced by the re-establishment of T3, T3/T4, and TSH values as well as ALT and AST activities. Interestingly, individual or concurrent supplementation of the atrazine group with silymarin and garlic extract prevented the down-regulation in hepatic iodothyronine deiodinase type 1. These effects were coupled with the repletion of serum and hepatic antioxidants and the amelioration of lipid peroxidation. In addition, current natural products markedly alleviated weight gain, dyslipidemia, hyperglycemia, glucose intolerance, and insulin resistance. Notably, a cocktail of silymarin and garlic extract exerted superior protection against atrazine-triggered deterioration of thyroid, hepatic, and metabolic functioning to individual treatments. Present findings pinpoint the prophylactic and synergistic influence of silymarin and garlic extract combinatorial regimen on thyroid activation and body metabolism via enhancing antioxidant potential, maintaining hepatic function, and iodothyronine deiodinase type 1.
Subject(s)
Atrazine , Garlic , Silymarin , Rats , Animals , Antioxidants/pharmacology , Antioxidants/metabolism , Garlic/metabolism , Atrazine/toxicity , Silymarin/pharmacology , Thyroid Hormones/metabolism , Thyroid Hormones/pharmacology , Iodide Peroxidase/metabolism , Iodide Peroxidase/pharmacology , LiverABSTRACT
BACKGROUND: Hashimoto thyroiditis (HT) is a common autoimmune thyroid disease for which there is no specific treatment. Oral levothyroxine sodium tablets significantly improved thyroid function but did not promote a reduction in thyroid-related antibody concentrations. Acupuncture can improve clinical symptoms and thyroid function in HT patients, reduce serum TPOAb and TGAb levels in HT patients, and improve patients' quality of life. METHODS: We conducted a systematic review and meta-analysis to evaluate the effect of acupuncture versus levothyroxine sodium tablets on Hashimoto thyroiditis. We searched Web of Science, Embase, China National Knowledge Infrastructure, WanFang, VIP, SinoMed and the Cochrane Central Registry of Controlled Trials to identify candidate randomized controlled trials (RCTs). RESULTS: A total of 1020 patients participated in 14 randomized controlled trials. The results of meta-analysis showed that acupuncture regulated TPOAb content (mean difference [MD]â =â -63.18, 95%CIâ =â -91.73 to -34.62, Pâ <â .00001), TGAb content (MDâ =â -68.56, 95%CIâ =â -101.55 to -35.57, Pâ <â .00001), serum free triiodothyronine (FT3) content (MDâ =â 0.74, 95%CIâ =â 0.20 to 1.27, Pâ <â .00001), serum free thyroxine (FT4) content (MDâ =â 1.10, 95%CIâ =â 0.29 to 1.92, Pâ <â .00001), TSH content (MDâ =â -2.16, 95%CIâ =â -3.14 to -1.19, Pâ <â .00001) had a significant effect. CONCLUSION: Compared with levothyroxine sodium tablets alone, acupuncture can significantly regulate the contents of TPOAb, TGAb, FT3, FT4 and TSH.
Subject(s)
Acupuncture Therapy , Hashimoto Disease , Humans , Hashimoto Disease/drug therapy , Thyroxine/therapeutic use , Thyroid Hormones , ThyrotropinABSTRACT
Unlike other thyroid hormone receptors (THRs), the beta 2 isoform (THRB2) has a restricted expression pattern and is uniquely and abundantly phosphorylated at a conserved serine residue S101 (S102 in humans). Using tagged and or phosphorylation-defective (S101A) THRB2 mutant mice, we show that THRB2 is present in a large subset of POMC neurons and mitigates ROS accumulation during ROS-triggering events, such as fasting/refeeding or high fat diet (HFD). Excessive ROS accumulation in mutant POMC neurons was accompanied by a skewed production of orexigenic/anorexigenic hormones, resulting in elevated food intake. The prolonged exposure to pathogenic hypothalamic ROS levels during HFD feeding lead to a significant loss of POMC neurons in mutant versus wild-type (WT) mice. In cultured cells, the presence of WT THRB2 isoform, but not other THRs, or THRB2S101A, reduced ROS accumulation upon exogenous induction of oxidative stress by tert-butyl hydroperoxide. The protective function of phospho-THRB2 (pTHRB2) did not require thyroid hormone (TH), suggesting a TH-independent role of the THRB2 isoform, and phospho-S101 in particular, in regulating oxidative stress. We propose that pTHRB2 has a fundamental role in neuronal protection against ROS cellular damage, and mitigates hypothalamic pathological changes found in diet-induced obesity.
Subject(s)
Hypothalamus , Pro-Opiomelanocortin , Humans , Mice , Animals , Reactive Oxygen Species/metabolism , Phosphorylation , Pro-Opiomelanocortin/metabolism , Hypothalamus/metabolism , Feeding Behavior , Thyroid Hormones/metabolism , Diet, High-Fat , Receptors, Thyroid Hormone/metabolism , Protein Isoforms/metabolism , Mice, Inbred C57BLABSTRACT
The mother's thyroid hormone status during gestation and the first few months after delivery can play a crucial role in maturation during the brain development of the child. Transient abnormalities in thyroid function at birth indicate developmental and cognitive disorders in adulthood. Choline supplementation during gestation and the perinatal period in rats causes long-lasting memory improvement in the offspring. However, it remains unclear whether choline is able to restore the deficits in rats with maternal hypothyroidism. The aim of this study was to evaluate the effects of choline supplementation on the alteration of cognitive-behavioral function, long-term potentiation (LTP), and morphological changes as well as apoptosis in pre-pubertal offspring rats. To induce hypothyroidism, 6-propyl-2-thiouracil was added to the drinking water from the 6th day of gestation to the 21st postnatal day (PND). Choline treatment was started twice a day on the first day of the gestation until PND 21 via gavage. LTP recording and Morris water maze (MWM) test were conducted at PND 28. Then, the rats were sacrificed to assess their brains. The results revealed that developmental thyroid hormone deficiency impaired spatial learning and memory and reduced LTP (both: P < 0.001). Choline treatment alleviated LTP (P < 0.001), as well as learning and memory deficits (P < 0.01) in both male and female hypothyroid rats. However, no significant changes were observed in the number of caspase-3 stained cells in choline-receiving hypothyroid groups. The results revealed that developmental thyroid hormone deficiency impaired spatial learning and memory and reduced LTP. Choline treatment alleviated LTP, as well as learning and memory deficits in both male and female hypothyroid rats.
Subject(s)
Hypothyroidism , Long-Term Potentiation , Humans , Pregnancy , Child , Rats , Animals , Male , Female , Mothers , Hypothyroidism/complications , Hypothyroidism/drug therapy , Thyroid Hormones/pharmacology , Hippocampus , Memory Disorders/etiology , Cognition , Apoptosis , Choline/therapeutic use , Choline/pharmacology , Dietary Supplements , Maze LearningABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Goiters are enlargements of the thyroid gland and are a global public issue. Quemeiteng granule (QMTG) is a traditional Chinese medicine (TCM) formula used to treat goiter in Yunnan Province. However, the effectiveness and underlying mechanism of these treatments have not been fully elucidated. AIM OF THE STUDY: This study aimed to investigate the therapeutic effects of QMTG on goiter and the downstream regulatory mechanisms. MATERIALS AND METHODS: In this study, we first evaluated the antigoiter efficacy of QMTG through biochemical indices [body weight, thyroid coefficient, triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH)] and hematoxylin-eosin (HE) staining in a Propylthiouracil (PTU)-induced model. Based on microRNA sequencing (miRNA-seq) and bioinformatics analysis, key miRNA was screened out. A dual-luciferase reporter assay was performed to confirm the transcriptional regulation of the target gene by the miRNA. The viability of rat thyroid microvascular endothelial cells (RTMECs) and human thyroid microvascular endothelial cells (HTMECs) was assessed using the CCK-8 assays. The migration and angiogenesis of RTMECs and HTMECs were visualized through tube formation and wound scratch assays. Proteins involved in angiogenesis and the ERK pathway were assessed via Western blotting. RESULTS: QMTG significantly increased body weight, decreased the thyroid coefficient, increased the levels of T3, T4, FT3 and FT4 and reduced TSH levels in rats with goiter. QMTG also promoted the morphological recovery of thyroid follicles. MiR-217-5p was identified as a key miRNA. Our studies revealed that miR-217-5p directly targets FGF2 and that QMTG promotes the recovery of thyroid hormone (TH) levels and morphological changes in the thyroid, suppresses thyroid microvascular endothelial cell vitality, tube formation and migration, and reduces the expression of VEGF, Ang-1 and VCAM-1 triggered by miR-217-5p, thereby inhibiting the Ras/MEK/ERK cascade through FGF2. CONCLUSIONS: Our experiments demonstrated that the QMTG had therapeutic effects on goiter. These effects were attributed to the inhibition of ERK pathway-induced proliferation and angiogenesis through the targeting of FGF2 by miR-217-5p.
Subject(s)
Goiter , MicroRNAs , Humans , Rats , Animals , MAP Kinase Signaling System , Fibroblast Growth Factor 2/metabolism , Triiodothyronine/pharmacology , Thyroxine , Endothelial Cells/metabolism , Angiogenesis , China , MicroRNAs/genetics , MicroRNAs/metabolism , Thyroid Hormones , Goiter/drug therapy , Cell Proliferation , Thyrotropin/metabolism , Body WeightABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Scrophulariae Radix (Xuanshen [XS]) has been used for several years to treat hyperthyroidism. However, its effective substances and pharmacological mechanisms in the treatment of hyperthyroidism and thyroid hormone-induced liver and kidney injuries have not yet been elucidated. AIM OF THE STUDY: This study aimed to explore the pharmacological material basis and potential mechanism of XS therapy for hyperthyroidism and thyroid hormone-induced liver and kidney injuries based on network pharmacology prediction and experimental validation. MATERIALS AND METHODS: Based on 31 in vivo XS compounds identified using ultra-performance liquid chromatography tandem quadruple exactive orbitrap high-resolution accurate-mass spectrometry (UPLC-QE-HRMS), a network pharmacology approach was used for mechanism prediction. Systematic networks were constructed to identify the potential molecular targets, biological processes (BP), and signaling pathways. A component-target-pathway network was established. Mice were administered levothyroxine sodium through gavage for 30 d and then treated with different doses of XS extract with or without propylthiouracil (PTU) for 30 d. Blood, liver, and kidney samples were analyzed using an enzyme-linked immunosorbent assay (ELISA) and western blotting. RESULTS: A total of 31 prototypes, 60 Phase I metabolites, and 23 Phase II metabolites were tentatively identified in the plasma of rats following the oral administration of XS extract. Ninety-six potential common targets between the 31 in vivo compounds and the diseases were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that Bcl-2, BAD, JNK, p38, and ERK1/2 were the top targets. XS extract with or without PTU had the following effects: inhibition of T3/T4/fT3/fT4 caused by levothyroxine; increase of TSH levels in serum; restoration of thyroid structure; improvement of liver and kidney structure and function by elevating the activities of anti-oxidant enzymes catalase (CAT),superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px); activation anti-apoptotic proteins Bcl-2; inhibition the apoptotic protein p-BAD; downregulation inflammation-related proteins p-ERK1/2, p-JNK, and p-p38; and inhibition of the aggregation of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6, as well as immune cells in the liver. CONCLUSION: XS can be used to treat hyperthyroidism and liver and kidney injuries caused by thyroid hormones through its anti-oxidant, anti-inflammatory, and anti-apoptotic properties. In addition, serum pharmacochemical analysis revealed that five active compounds, namely 4-methylcatechol, sugiol, eugenol, acetovanillone, and oleic acid, have diverse metabolic pathways in vivo and exhibit potential as effective therapeutic agents.
Subject(s)
Drugs, Chinese Herbal , Hyperthyroidism , Rats , Mice , Animals , Antioxidants/pharmacology , Network Pharmacology , Liver , Thyroid Hormones/metabolism , Hyperthyroidism/chemically induced , Hyperthyroidism/drug therapy , Thyroxine , Kidney/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Anti-Inflammatory Agents/pharmacology , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/metabolism , Molecular Docking SimulationABSTRACT
BACKGROUND: Melissa officinalis (MO) is a well-known medicinal plant species used in the treatment of several diseases; it is widely used as a vegetable, adding flavour to dishes. This study was designed to evaluate the therapeutic effect of MO Extract against hyperthyroidism induced by Eltroxin and γ-radiation. METHODS: Hyperthyroidism was induced by injecting rats with Eltroxin (100 µg/kg/ day) for 14 days and exposure to γ-radiation (IR) (5 Gy single dose). The hyperthyroid rats were orally treated with MO extract (75 mg/kg/day) at the beginning of the second week of the Eltroxin injection and continued for another week. The levels of thyroid hormones, liver enzymes and proteins besides the impaired hepatic redox status and antioxidant parameters were measured using commercial kits. The hepatic gene expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and its inhibitor Kelch-like ECH-associated protein-1(Keap-1) in addition to hepatic inflammatory mediators including tumor necrosis factor-α (TNF- α), Monocyte chemoattractant protein-1 (MCP-1) and fibrogenic markers such as transforming growth factor-beta1 (TGF-ß1) were determined. RESULTS: MO Extract reversed the effect of Eltroxin + IR on rats and attenuated the thyroid hormones. Moreover, it alleviated hyperthyroidism-induced hepatic damage by inhibiting the hepatic enzymes' activities as well as enhancing the production of proteins concomitant with improving cellular redox homeostasis by attenuating the deranged redox balance and modulating the Nrf2/Keap-1 pathway. Additionally, MO Extract alleviated the inflammatory response by suppressing the TNF- α and MCP-1 and prevented hepatic fibrosis via Nrf2-mediated inhibition of the TGF-ß1/Smad pathway. CONCLUSION: Accordingly, these results might strengthen the hepatoprotective effect of MO Extract in a rat model of hyperthyroidism by regulating the Nrf-2/ Keap-1 pathway.
Subject(s)
Hyperthyroidism , Liver Diseases , Melissa , Plant Extracts , Animals , Rats , Gene Expression , Hyperthyroidism/complications , Hyperthyroidism/drug therapy , Inflammation/metabolism , Liver , Melissa/chemistry , NF-E2-Related Factor 2/metabolism , Oxidation-Reduction , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Thyroid Hormones/metabolism , Thyroxine/genetics , Thyroxine/metabolism , Transforming Growth Factor beta1/metabolism , Liver Diseases/etiology , Liver Diseases/therapyABSTRACT
The biosynthesis of thyroid hormones is essential for brain and neurological development. It requires iodine as a key component but is also influenced by other nutrients. Evidence for the combined nutrient status in relation to thyroid hormones during pregnancy is limited. We aimed to investigate the joint associations of iodine, selenium, zinc, calcium, magnesium and iron with maternal thyroid functions in 489 pregnant women from Hangzhou, China. Serum levels of six essential minerals and thyroid function parameters were measured during the first antenatal visit. Linear regression, quantile g-computation and Bayesian kernel machine regression were used to explore the individual and joint relationships between the six minerals and thyroid hormones. Linear regression analyses revealed that calcium was positively associated with free triiodothyronine (FT3). Zinc was positively associated with free thyroxine (FT4). Iodine was negatively associated with thyroid-stimulating hormone (TSH) and positively associated with FT3 and FT4. The quantile g-computation and BKMR models indicated that the joint nutrient concentration was negatively associated with TSH and positively associated with FT3 and FT4. Among the six minerals, iodine contributed most to thyroid function. The findings suggested that maintaining the appropriate concentration of minerals, either as individuals or a mixture, is important for thyroid health during pregnancy.
Subject(s)
Iodine , Selenium , Female , Humans , Pregnancy , Pregnant Women , Calcium , Bayes Theorem , Thyroid Function Tests , Thyroid Hormones , Thyrotropin , Zinc , China , ThyroxineABSTRACT
Equine thyroid disorders pose a diagnostic challenge in clinical practice because of the effects of nonthyroidal factors on the hypothalamic-pituitary-thyroid axis, and the horse's ability to tolerate wide fluctuations in thyroid hormone concentrations and survive without a thyroid gland. While benign thyroid tumours are common in older horses, other disorders like primary hypothyroidism or hyperthyroidism in adult horses and congenital hypothyroidism in foals are rare. There is a common misunderstanding regarding hypothyroidism in adult horses, especially when associated with the clinical profile of obesity, lethargy, and poor performance observed in dogs and humans. Low blood thyroid hormone concentrations are often detected in horses as a secondary response to metabolic and disease states, including with the nonthyroidal illness syndrome; however, it is important to note that low thyroid hormone concentrations in these cases do not necessarily indicate hypothyroidism. Assessing equine thyroid function involves measuring thyroid hormone concentrations, including total and free fractions of thyroxine (T4) and triiodothyronine (T3); however, interpreting these results can be challenging due to the pulsatile secretion of thyroid hormones and the many factors that can affect their concentrations. Dynamic testing, such as the thyrotropin-releasing hormone stimulation test, can help assess the thyroid gland response to stimulation. Although true hypothyroidism is extremely rare, thyroid hormone supplementation is commonly used in equine practice to help manage obesity and poor performance. This review focuses on thyroid gland pathophysiology in adult horses and foals, interpretation of blood thyroid hormone concentrations, and evaluation of horses with thyroid disorders. It also discusses the use of T4 supplementation in equine practice.
Subject(s)
Dog Diseases , Horse Diseases , Hypothyroidism , Thyroid Diseases , Humans , Horses , Animals , Dogs , Thyrotropin/physiology , Thyroid Hormones/physiology , Thyroid Diseases/diagnosis , Thyroid Diseases/drug therapy , Thyroid Diseases/veterinary , Thyroxine/therapeutic use , Triiodothyronine/physiology , Hypothyroidism/diagnosis , Hypothyroidism/veterinary , Obesity/veterinary , Horse Diseases/diagnosis , Horse Diseases/drug therapy , Dietary SupplementsABSTRACT
Background: Recent successes with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) for the treatment of solid malignancies have paved the way for a new era of combined therapy. A common side effect seen with each of these classes of treatment is thyroid dysfunction, with rates estimated at 30-40% for TKI and 10-20% for ICI. However, little is known about the effect of combined ICI+TKI therapy on thyroid function. Therefore, this study evaluated the incidence, clinical features, and risk factors for developing thyroid abnormalities during ICI+TKI therapy and the relationship to cancer outcomes. Methods: We conducted a retrospective cohort study of patients treated with combination ICI+TKI cancer therapy at City of Hope Comprehensive Cancer Center from 2017 to 2023 who had pretreatment normal thyrotropin (TSH) levels. Primary analyses assessed the frequency, timing, and severity of thyroid function test abnormalities during ICI+TKI cancer therapy, and the requirement for thyroid hormone replacement. Secondary analyses evaluated risk factors for the development of thyroid dysfunction, including sex and drug regimen, and the association with cancer progression-free survival or overall survival. Univariable and multivariable models were used. Results: There were 106 patients who received ICI+TKI therapy with a median age of 63.5 years and a median follow-up of 12.8 months (interquartile range [IQR] 5.9-20.9). Notably, 63.2% (67/106) developed thyroid function abnormalities during ICI+TKI therapy, including 11 (10.4%) with hyperthyroidism, 42 (39.6%) with subclinical hypothyroidism (SCHypo), and 14 (13.2%) with overt hypothyroidism. The onset of thyroid dysfunction occurred at a median of 7 weeks (IQR 3.1-9.0) after start of ICI+TKI treatment for hyperthyroidism, 8.0 weeks (IQR 3.0-19.0) for SCHypo, and 8.1 weeks (IQR 5.9-9.1) for overt or worsening hypothyroidism. Hyperthyroidism resolved to hypothyroidism or normal TSH without intervention in all subjects, suggesting thyroiditis, and hypothyroidism was readily treated with thyroid hormone replacement. Conclusions: Thyroid dysfunction is a frequent adverse event in individuals treated with combination ICI+TKI therapy, with our data suggesting a rapid onset and higher incidence than previously seen with ICI or TKI therapy alone. Therefore, close monitoring of thyroid function during initial therapy and multidisciplinary care with endocrinology are recommended to facilitate early detection and initiation of thyroid hormone replacement in these patients.
Subject(s)
Hyperthyroidism , Hypothyroidism , Neoplasms , Thyroid Diseases , Humans , Middle Aged , Immune Checkpoint Inhibitors/adverse effects , Thyroid Function Tests , Retrospective Studies , Hypothyroidism/chemically induced , Hypothyroidism/epidemiology , Hypothyroidism/complications , Thyroid Diseases/diagnosis , Hyperthyroidism/drug therapy , Neoplasms/drug therapy , Thyrotropin/therapeutic use , Thyroid Hormones/therapeutic useABSTRACT
CONTEXT: Combination therapy with levothyroxine and liothyronine (LT4 + LT3) and desiccated thyroid extract (DTE) make up >10% of new thyroid hormone (TH) prescriptions in the United States. OBJECTIVE: To assess health care utilization related to cardiovascular disease (CVD) and bone health (BH) events (atrial fibrillation [AF], heart failure [HF], myocardial infarction [MI], stroke, and osteoporosis/fractures [FX]) in participants taking LT4+LT3 or DTE surveyed in the Medical Expenditure Panel Survey database. MATERIALS AND METHODS: Multi-year cross-sectional analysis examining 5437 participants (≥18 years old) treated with LT4, LT4+LT3, or DTE between 2016 and 2020. Health care utilization was assessed through outpatient, emergency, and hospital visits for AF, HF, MI, stroke, FX, and a composite index. A weighted analysis provided national estimates of health care utilization parameters. Utilization was re-analyzed following propensity score-based matching to balance sociodemographic and clinical covariates between treatment groups. Additionally, provider type and specialty data were obtained from visits associated with TH prescriptions. RESULTS: 5106 participants were treated with LT4 monotherapy, 252 with DTE, and 79 with LT4 + LT3. Prevalence of combined outpatient CVD and BH-related care utilization was lower among DTE/LT4+LT3 vs LT4 users (3.5% vs 7.7%; P = .008). There were no differences in emergency/hospital events. After covariate balancing, CVD and BH-related care utilization was similar between groups in outpatient and emergency/hospital settings. LT3 and DTE made up 7.6% of all TH prescriptions. For visits associated with DTE prescriptions, nurse practitioners and alternative medicine professionals were more likely to be identified as the primary provider type. CONCLUSION: No significant differences in CVD- and BH-related health care utilization were identified between LT4 and DTE/LT4+LT3 users after covariate balancing. Non-MD providers were more likely to prescribe DTE.
Subject(s)
Cardiovascular Diseases , Hypothyroidism , Stroke , Humans , Adolescent , Hypothyroidism/drug therapy , Cross-Sectional Studies , Thyroid Hormones/therapeutic use , Thyroxine/therapeutic use , Triiodothyronine , Patient Acceptance of Health Care , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/epidemiology , Stroke/drug therapyABSTRACT
Thyroid hormone in the hypothalamus acts as a key determinant of seasonal transitions. Thyroid hormone-levels in the brain are mainly regulated by the hypothalamic tanycytes and pituitary pars tuberalis (PT)-specific cells. TSHß produced by the PT-specific cells stimulates Dio2 expression and decreases Dio3 expression of the tanycytes. Both tanycytes and PT-specific cells in photosensitive animals exhibit remarkable changes of morphological appearance and expressions of genes and proteins under different photoperiods. Long photoperiods induce increased gene- and protein-expressions and active features. Short photoperiods cause the decreased gene- and protein-expressions and inactive features. In the PT, expressions of TSHß, common α-subunit of glycoprotein hormones (α-GSU), and MT1 receptor of melatonin receptors and eyes absent 3 change under different photoperiods. Diurnal rhythms of α-GSU mRNA expression are observed in the PT of Djungarian hamsters. Hes1, Nkx2.1, and LIM homeodomain gene 2 (Lhx2) are involved in the differentiation of PT. In the hypothalamic tanycytes, expressions of Dio2, Dio3, vimentin, serine/threonine kinase 33, GPR50, Nestin, Retinoid signaling genes (retinaldehyde dehydrogenase 1, cellular retinol binding protein 1, and Stra6), monocarboxylate transporter 8, and neural cell adhesion molecule change under different photoperiods. Rax, Lhx2, Nfia/b/x, and fibroblast growth factor 10 are involved in the differentiation of tanycytes.
Subject(s)
Ependymoglial Cells , Photoperiod , Cricetinae , Animals , LIM-Homeodomain Proteins/metabolism , Ependymoglial Cells/metabolism , Hypothalamus/metabolism , Thyroid Hormones/metabolismABSTRACT
The search for a natural antimicrobial agent is ongoing and critical because of the rise and rapid proliferation of antibiotic-resistant pathogenic bacteria. The current study aims to examine the effect of Paenibacillus polymyxa AM20 as an alternative antibiotic and feed additive on Indian river broiler performance, digestive enzymes, thyroid hormones, lipid profile, hepatosomatic index, immunological response, gut bacteria, and antioxidant parameters. The bacterial isolate AM20 was identified at the gene level by isolating DNA and using PCR to detect genes. Based on 16S rRNA gene sequence analysis, the bacterial isolate was identified as Paenibacillus polymyxa. One hundred twenty Indian river broilers (1-day old) were randomly divided into 4 groups of 10 chicks each, with 3 replicates. The control group was fed a basal diet only, while the other 3 were administered control diets supplemented with P. polymyxa at 3 concentrations: 0.5, 1, and 1.5 mg/kg. The findings revealed that all groups that received graded amounts of P. polymyxa increased all growth parameters throughout the study. P. polymyxa treatment at 1.5 mg/kg increased body gain by 9% compared to the control due to increased feed intake (P = 0.0001), growth rate (P = 0.0001), and decreased feed conversion ratio. Compared to the control group, P. polymyxa (1.5 mg/kg) enhanced kidney functions in chickens by reducing uric acid and creatinine levels (P = 0.0451). Compared to the control group, alanine aminotransferase and aspartate transaminase levels in the liver were significantly reduced at all P. polymyxa doses. Liver function values were highest for P. polymyxa at 1.5 mg/kg. Compared to the control group, those whose diets included P. polymyxa had significantly better blood cholesterol levels, high-density lipoprotein, low-density lipoprotein, immunological response, thyroid function, and gut microbiota. In general, broiler chickens' economic efficiency was improved by including P. polymyxa in their diet, which also improved their growth performance, carcass dressing, specific blood biochemical levels and enzymes, and the composition of the gut microbiota.
Subject(s)
Paenibacillus polymyxa , Probiotics , Animals , Antioxidants/metabolism , Chickens/physiology , RNA, Ribosomal, 16S , Diet/veterinary , Dietary Supplements , Probiotics/pharmacology , Anti-Bacterial Agents , Immunity , Thyroid Hormones , Lipids , Animal Feed/analysisABSTRACT
Background: The importance of thyroid hormones (THs) for peripheral body temperature regulation has been long recognized, as medical conditions such as hyper- and hypothyroidism lead to alterations in body temperature and energy metabolism. In the past decade, the brain actions of THs and their respective nuclear receptors, thyroid hormone receptor α1 (TRα1) and thyroid hormone receptor beta (TRß), coordinating body temperature regulation have moved into focus. However, the exact roles of the individual TR isoforms and their precise neuroanatomical substrates remain poorly understood. Methods: Here we used mice expressing a mutant TRα1 (TRα1+m) as well as TRß knockouts to study body temperature regulation using radiotelemetry in conscious and freely moving animals at different ambient temperatures, including their response to oral 3,3',5-triiodothyronine (T3) treatment. Subsequently, we tested the effects of a dominant-negative TRα1 on body temperature after adeno-associated virus (AAV)-mediated expression in the hypothalamus, a region known to be involved in thermoregulation. Results: While TRß seems to play a negligible role in body temperature regulation, TRα1+m mice had lower body temperature, which was surprisingly not entirely normalized at 30°C, where defects in facultative thermogenesis or tail heat loss are eliminated as confounding factors. Only oral T3 treatment fully normalized the body temperature profile of TRα1+m mice, suggesting that the mutant TRα1 confers an altered central temperature set point in these mice. When we tested this hypothesis more directly by expressing the dominant-negative TRα1 selectively in the hypothalamus via AAV transfection, we observed a similarly reduced body temperature at room temperature and 30°C. Conclusion: Our data suggest that TRα1 signaling in the hypothalamus is important for maintaining body temperature. However, further studies are needed to dissect the precise neuroanatomical substrates and the downstream pathways mediating this effect.
Subject(s)
Hypothalamus , Receptors, Thyroid Hormone , Animals , Mice , Body Temperature , Hypothalamus/metabolism , Hypothyroidism/metabolism , Receptors, Thyroid Hormone/metabolism , Thyroid Hormone Receptors alpha/metabolism , Thyroid Hormones , Triiodothyronine/pharmacology , Triiodothyronine/metabolismABSTRACT
We report here two patients exhibiting a combination of falsely elevated serum levels of free thyroxine (FT4), free triiodothyronine (FT3), and thyrotropin receptor antibodies (TRAb), measured using Elecsys assay kits (Roche Diagnostics GmbH). The first patient was a 74-year-old man misdiagnosed with Graves' disease and treated with methimazole. The second patient was a 48-year-old woman whose serum FT4 and FT3 concentrations were found to be high during a blood test. These patients denied taking biotin or any other supplements. Further detailed examination, including a heterophilic blocking tube test, revealed the presence of serum antibodies. The abnormal reactions were observed only using the improved assay kits using ruthenium (Ru) sulfonate instead of Ru as a chemiluminescent agent. Therefore, serum antibodies to the Ru sulfonate complex caused the pseudo-high levels of FT4, FT3, and TRAb. To our knowledge, this is the first report showing that antibodies to the Ru sulfonate complex in the electrochemiluminescence immunoassay can cause falsely elevated levels of the combination, leading to discrepant thyroid function test results. We emphasize that in cases of abnormal test results, alternative assay methods should be considered for further examination; unusual test results should not be impulsively interpreted, even when using revised assay kits.
Subject(s)
Graves Disease , Ruthenium , Male , Female , Humans , Middle Aged , Aged , Thyroid Function Tests , Thyroxine , Thyroid Hormones , Triiodothyronine , Antibodies, Viral , ThyrotropinABSTRACT
BACKGROUND: The American Thyroid Association updated guidelines in 2015 to allow lobectomy for low-risk thyroid cancers. The objectives of this study were (1) to determine thyroid hormone supplementation rates after lobectomy and (2) to evaluate the effect of the American Thyroid Association guideline change on lobectomy and hormone supplementation rates among thyroid cancer patients. METHODS: The Merative MarketScan Databases was used to identify adult (≥age 18) patients who underwent thyroidectomy for benign nodules or thyroid cancer. The association between indication for surgery and postoperative thyroid hormone supplementation was examined using χ2 analyses and multivariable logistic regression models. Among patients with thyroid cancer, lobectomy and hormone supplementation rates were compared in the periods before (2008-2015) and after the guideline change (2016-2019). RESULTS: Of the 81,926 patients identified, 33,756 (41.2%) underwent thyroid lobectomy, 45,104 (55.1%) underwent total thyroidectomy, and 3,066 (3.7%) underwent completion thyroidectomy. Patients who underwent lobectomy for malignancy were significantly more likely to require hormone supplementation (59.3% vs 39.4% [P < .001], adjusted odds ratio 2.34 [95% confidence interval 2.20-2.48]) compared to those with benign disease. Compared to the 2008 to 2015 period, the proportion of patients who underwent lobectomy for thyroid cancer was higher in the 2016 to 2019 period (34.3% vs 30.3%, P < .001), with fewer patients requiring completion thyroidectomy (25.6% vs 29.8%, P < .001) and thyroid hormone supplementation (56.9% vs 60.1%, P = .04). CONCLUSION: The postoperative thyroid hormone supplementation rate was significantly higher in patients who had thyroid cancers compared to benign diseases. After the American Thyroid Association guidelines changed, lobectomy rates increased significantly without a concomitant increase in the completion of thyroidectomy.
Subject(s)
Thyroid Neoplasms , Thyroidectomy , Adult , Humans , Adolescent , Thyroidectomy/adverse effects , Retrospective Studies , Thyroid Neoplasms/surgery , Thyroid Neoplasms/pathology , Thyroid Hormones , Dietary SupplementsABSTRACT
Selenium (Se), an essential trace element, is fundamental to human health, playing an important role in the formation of thyroid hormones, DNA synthesis, the immune response, and fertility. There is a lack of comprehensive epidemiological research, particularly the serum Se concetration in healthy infants and preschool children compared to the estimated dietary Se intake. However, Se deficiencies and exceeding the UL have been observed in infants and preschool children. Despite the observed irregularities in Se intake, there is a lack of nutritional recommendations for infants and preschool children. Therefore, the main objective of this literature review was to summarize what is known to date about Se levels and the risk of deficiency related to regular consumption in infants and preschool children.
Subject(s)
Selenium , Trace Elements , Infant , Humans , Child, Preschool , Nutritional Status , Diet , Thyroid HormonesABSTRACT
<b>Background and Objective:</b> The negative effects of preservatives, such as sodium benzoate, have received increasing global attention. The objective of the study was to investigate the potential protective effects of nano-selenium (nano-Se) on thyroid functions, oxidative stress and inflammatory cytokine responses of albino rats. <b>Materials and Methods:</b> Thirty-five male rats were divided into five groups, 7 rats in each: GI: A control group, GII: Corn oil, GIII: Nano-selenium, GIV: Sodium benzoate, GV: Selenium nanoparticles followed with sodium benzoate. At the end of study, sera were separated from all rats for estimation of MDA, GSH, GSH-PX, glucose, interleukin-1ß, TSH, T3, FT3, T4 and FT4. All data were statistically analyzed using Analysis of Variance (ANOVA). <b>Results:</b> Sodium benzoate treatment showed opposite effects as it decreased levels of T3, FT3, F4, FT4, GSH and GSH-PX. On the contrary, it increased serum levels of TSH, MDA, NO, glucose and IL-1β when compared to the control group. Whereas, nano-selenium promoted a significant increase in levels of thyroid hormones T3, T4 and FT4, upgrading GSH and GSH-PX. While it reduced TSH, MDA, NO, glucose and IL-1β levels when compared to the sodium benzoate group. <b>Conclusion:</b> Nano-selenium treatment as a protector showed the ability to reduce lipid peroxidation and restore glutathione peroxidase activity, thus, selenium complex at nano-level can reduce oxidative stress and damage of thyroid hormones caused by sodium benzoate administration.
Subject(s)
Selenium , Rats , Male , Animals , Selenium/pharmacology , Sodium Benzoate/pharmacology , Thyroid Gland/metabolism , Prospective Studies , Antioxidants/pharmacology , Antioxidants/metabolism , Oxidative Stress , Thyroid Hormones/pharmacology , Thyrotropin/pharmacology , GlucoseABSTRACT
Adequate iodine intake is of crucial importance in pregnancy to meet the thyroid hormone needs of both mother and fetus. In the present study, undertaken as a part of the surveillance actions following the introduction in Italy of a national salt iodination program in 2005, the iodine intake was investigated in 123 pregnant women and 49 control women living in the same area of central Italy. All the participants were screened for urinary iodine concentration (UIC), serum level of thyrotropin, free-thyroxine, free-triiodothyronine, and thyroid volume. Moreover, they were provided with a questionnaire on the use of iodine-containing salt or supplements. Control women had a median UIC of 102 µg/L, consistent with an iodine sufficiency, while in pregnant women the median UIC value was 108 µg/L, lower than the endorsed UIC of 150 µg/L. In addition, pregnant women showed a significantly increased median thyroid volume compared to controls. Interestingly, the median UIC did not differ between pregnant women not using iodine-containing salt or supplements and those regularly consuming iodized salt alone, while pregnant women with a daily intake of iodine-containing supplements had an adequate median UIC (168 µg/L). In conclusion, the data reported here showed that pregnant women and their fetuses are still exposed to the detrimental effects of iodine deficiency and that the consumption of iodine-containing supplements should be recommended in pregnancy.
Subject(s)
Iodine , Pregnant Women , Female , Humans , Pregnancy , Nutritional Status , Thyroid Gland , Sodium Chloride, Dietary , Thyroid HormonesABSTRACT
Icariin (ICA) is a natural flavonoid isolated from the traditional Chinese medicinal herb, Epimedium brevicornu Maxim. Although previous studies have reported that ICA exhibits various pharmacological activities, little is known about its toxicology. Herein, zebrafish embryos were exposed to ICA at 0, 2.5, 10, and 40 µM. In developmental analysis, reduced hatching rates, decreased body length, and abnormal swim bladder were found after treatment with 10 and 40 µM ICA. In addition, the ability of locomotor behavior was impaired by ICA. Two important thyroid hormones (THs), triiodothyronine (T3) and thyroxine (T4), were tested. The exposure resulted in a remarkable alteration of T4 level and a significant decrease of the T3/T4 ratio in the 40 µM, indicating thyroid endocrine disruption. Furthermore, gene transcription analysis showed that genes involved in thyroid development (nkx2.1) and THs synthesis (tg) were up-regulated after ICA exposure. Significant down-regulation of iodothyronine deiodinase (dio1) was also observed in the 10 and 40 µM groups compared to the control. Taken together, our study first demonstrated that ICA caused developmental toxicity possibly through disrupting thyroid development and hormone synthesis. These results show that it is necessary to perform risk assessments of ICA in clinical practice.