Increase In T4 Levels Research Articles

Genetic Association Between Single Nucleotide Polymorphisms of the HLA-G Gene and Papillary Thyroid Carcinoma in Iraqi Patients

This study was designed to investigate the relationship between HLA-G gene SNPs in exons 2 and 8 and papillary thyroid carcinoma (PTC). Blood samples from 100 patients, categorized into pre- and post-radioactive therapy groups, and 50 healthy subjects were analyzed via PCR and direct sequencing for allele and genotype frequencies. PTC was eight times more prevalent in women. Thyroid assessment hormones exhibited reduced T3 levels pre- and post-radioactive iodine therapy and increased T4 levels post-therapy (49.80 ng/ml vs. control 16.84 ng/ml). Notably, TSH levels significantly decreased before and after therapy in PTC patients versus controls (P = 0.005). HLA-G gene SNPs were linked to PTC risk: in exon 2, genotype AA posed risk (OR = 16.10 and 10.58; P = 0.001) pre- and post-therapy, while homozygous TT in exon 8 increased risk (OR = 7.30; P = 0.001; OR = 4.41; P = 0.018), and heterozygous CT was protective (OR = 0.27; P = 0.016) before therapy. These findings suggest homozygous SNPs contribute to the genetic risk factors for PTC in the Iraqi population.

Effects of 4G Long-Term Evolution Electromagnetic Fields on Thyroid Hormone Dysfunction and Behavioral Changes in Adolescent Male Mice.

Radiofrequency electromagnetic fields (RF-EMFs) can penetrate tissues and potentially influence endocrine and brain development. Despite increased mobile phone use among children and adolescents, the long-term effects of RF-EMF exposure on brain and endocrine development remain unclear. This study investigated the effects of long-term evolution band (LTE) EMF exposure on thyroid hormone levels, crucial for metabolism, growth, and development. Four-week-old male mice (C57BL/6) were exposed to LTE EMF (whole-body average specific absorption rate [SAR] 4 W/kg) or a positive control (lead; Pb, 300 ppm in drinking water) for 4 weeks. Subsequently, the mice underwent behavioral tests including open field, marble burying, and nest building. Blood pituitary and thyroid hormone levels, and thyroid hormone-regulating genes within the hypothalamus-pituitary-thyroid (HPT) axis were analyzed. LTE exposure increased T3 levels, while Pb exposure elevated T3 and T4 and decreased ACTH levels. The LTE EMF group showed no gene expression alterations in the thyroid and pituitary glands, but hypothalamic Dio2 and Dio3 expressions were significantly reduced compared to that in the sham-exposed group. Pb exposure altered the hypothalamic mRNA levels of Oatp1c1 and Trh, pituitary mRNA of Trhr, and Tpo and Tg expression in the thyroid. In conclusion, LTE EMF exposure altered hypothalamic Dio2 and Dio3 expression, potentially impacting the HPT axis function. Further research is needed to explore RF-EMF's impacts on the endocrine system.

Features of the functioning of the hypothalamic-pituitary-thyroid axis in mice with Lewis carcinoma on the background of induced hyperthyroidism

Thyroid hormones (TH) influence the processes of cell proliferation and differentiation, but their role in the processes of carcinogenesis is contradictory. The purpose of the study. To study the effect of induced hyperthyroidism in mice of both sexes with intertwined Lewis carcinoma (LLC) on the activity of the hypothalamic-pituitary-thyroid axis (GGT). Materials and methods. The experimental model was mixed-sex mice of the C57BL/6 line with subcutaneously transplanted LLC on the background of induced hyperthyroidism (main group). Two control groups were used: control group I – mice with sodium liothyronine- induced hyperthyroidism and control group II – mice with subcutaneously transplanted LLC. On the 25th day after tumor transplantation, the level of thyrotropin- releasing hormone (TRH), thyroid- stimulating hormone (TSH), triiodothyronine (T3), total and free thyroxine (T4, FT4) was determined in the homogenates of GGT organs and in blood serum. Results. In female mice, hyperthyroidism caused an increase in the level of TRH in the hypothalamus and a decrease in TSH in the pituitary gland; in males, a decrease in TRH only in the hypothalamus. In control group II, euthyroid disorder syndrome developed: In mice of both sexes, serum levels of T4 and FT4 were found to decrease against the background of unchanged T3 levels and an increase in TSH content only in females. In the females of the main group, an increase in the level of TSH in the thyroid gland caused a decrease in T3 content in 73 % of animals against the background of normal T4 and elevated FT4 levels, in 27 % of females the T3 level increased. In males, in 73 % of the observations, the T3 level was increased against the background of high T4 and FT4 values and unchanged TSH levels. In the skin and LLC samples of the mice of the main group, an increase in T3 levels was noted. Conclusion. The growth of LLC against the background of hyperthyroidism is a process with multifactorial effects. High levels of T3 in blood serum and skin stimulated the proliferation of tumor cells, which led to the formation of subcutaneous tumors of a larger volume in the mice of the main group. Sex differences in the GGT response indicate different mechanisms that implement pathological processes.

Comparative study of the effects of different surface-coated silver nanoparticles on thyroid disruption and bioaccumulation in zebrafish early life

The widespread use of silver nanoparticles (AgNPs) in commercial and industrial applications has led to their increased presence in the environment, raising concerns about their ecological and health impacts. This study pioneers an investigation into the chronic versus short-term acute toxicological impacts of differently coated AgNPs on zebrafish, with a novel focus on the thyroid-disrupting effects previously unexplored. The results showed that acute toxicity ranked from highest to lowest as AgNO3 (0.128 mg/L), PVP-AgNPs (1.294 mg/L), Citrate-AgNPs (6.984 mg/L), Uncoated-AgNPs (8.269 mg/L). For bioaccumulation, initial peaks were observed at 2 days, followed by fluctuations over time, with the eventual highest enrichment seen in Uncoated-AgNPs and Citrate-AgNPs at concentrations of 13 and 130 μg/L. Additionally, the four exposure groups showed a significant increase in T3 levels, which was 1.28–2.11 times higher than controls, and significant changes in thyroid peroxidase (TPO) and thyroglobulin (TG) content, indicating thyroid disruption. Gene expression analysis revealed distinct changes in the HPT axis-related genes, providing potential mechanisms underlying the thyroid toxicity induced by different AgNPs. The higher the Ag concentration in zebrafish, the stronger the thyroid disrupting effects, which in turn affected growth and development, in the order of Citrate-AgNPs, Uncoated-AgNPs > AgNO3, PVP-AgNPs. This research underscores the importance of considering nanoparticle coatings in risk assessments and offers insights into the mechanisms by which AgNPs affect aquatic organisms' endocrine systems, highlighting the need for careful nanotechnology use and the relevance of these findings for understanding environmental pollutants' role in thyroid disease.

Sustained Pituitary T3 Production Explains the T4-mediated TSH Feedback Mechanism.

The regulation of thyroid activity and thyroid hormone (TH) secretion is based on feedback mechanisms that involve the anterior pituitary TSH and medial basal hypothalamus TSH-releasing hormone. Plasma T3 levels can be "sensed" directly by the anterior pituitary and medial basal hypothalamus; plasma T4 levels require local conversion of T4 to T3, which is mediated by the type 2 deiodinase (D2). To study D2-mediated T4 to T3 conversion and T3 production in the anterior pituitary gland, we used mouse pituitary explants incubated with 125I-T4 for 48 hours to measure T3 production at different concentrations of free T4. The results were compared with cultures of D1- or D2-expressing cells, as well as freshly isolated mouse tissue. These studies revealed a unique regulation of the D2 pathway in the anterior pituitary gland, distinct from that observed in nonpituitary tissues. In the anterior pituitary, increasing T4 levels reduced D2 activity slightly but caused a direct increase in T3 production. However, the same changes in T4 levels decreased T3 production in human HSkM cells and murine C2C12 cells (both skeletal muscle) and mouse bone marrow tissue, which reached zero at 50 pM free T4. In contrast, the increase in T4 levels caused the pig kidney LLC-PK1 cells and kidney fragments to proportionally increase T3 production. These findings have important implications for both physiology and clinical practice because they clarify the mechanism by which fluctuations in plasma T4 levels are transduced in the anterior pituitary gland to mediate the TSH feedback mechanism.

Thyroid axis participates in high-temperature-induced male sex reversal through its activation by the stress response.

Environmental changes alter the sex fate in about 15% of vertebrate orders, mainly in ectotherms such as fish and reptiles. However, the effects of temperature changes on the endocrine and molecular processes controlling gonadal sex determination are not fully understood. Here, we provide evidence that thyroid hormones (THs) act as co-players in heat-induced masculinization through interactions with the stress axis to promote testicular development. We first demonstrated that the thyroid axis (through thyroid-related genes and T3 levels) is highly active in males during the gonadal development in medaka (Oryzias latipes). Similarly, T3 treatments promoted female-to-male sex reversal in XX embryos. Subsequently, embryonic exposure to temperature-induced stress up-regulated the genes related to the thyroid and stress axes with a final increase in T3 levels. In this context, we show that blocking the stress axis response by the loss of function of the corticotropin-releasing hormone receptors suppresses thyroid-stimulating hormone expression, therefore, heat-induced activation of the thyroid axis. Thus, our data showed that early activation of the stress axis and, in consequence, the TH axis, too, leaves us with that both being important endocrine players in inducing female-to-male reversal, which can help predict possible upcoming physiological impacts of global warming on fish populations.

Sublethal Biochemical Effects of Polyethylene Microplastics and TBBPA in Experimentally Exposed Freshwater Shrimp Palaemonetes argentinus

The biochemical effects of sublethal exposure to polyethylene microplastics (PEM) of 40-48 µm particle size and the flame retardant tetrabromobisphenol A (TBBPA), a plastic additive, on the freshwater shrimp Palaemonetes argentinus were assessed. Here, we postulate that the use of enzyme and thyroid hormones as biomarkers contributes to the knowledge of the effects of microplastics and plastic additives on freshwater crustaceans. To address this, we evaluated the activities of acetylcholinesterase (AChE), glutathione S-transferase (GST), and carboxilesterase (CbE, using 1-naphthyl acetate (NA) as substrate) and levels of the thyroid hormones thyroxine (T4) and triiodothyronine (T3) after shrimp were exposed (for 96 h) to these xenobiotics at environmentally realistic concentrations. The results showed that the mixture of both xenobiotics led to a decrease in AChE and GST activities and increased T4 levels. We suggest that physiological processes could be compromised in freshwater organisms when exposed to microplastics and TBBPA together, and this could ultimately affect upper levels of the food web.

Single-cell profiling reveals Müller glia coordinate retinal intercellular communication during light/dark adaptation via thyroid hormone signaling.

Light adaptation enables the vertebrate visual system to operate over a wide range of ambient illumination. Regulation of phototransduction in photoreceptors is considered a major mechanism underlying light adaptation. However, various types of neurons and glial cells exist in the retina, and whether and how all retinal cells interact to adapt to light/dark conditions at the cellular and molecular levels requires systematic investigation. Therefore, we utilized single-cell RNA sequencing to dissect retinal cell-type-specific transcriptomes during light/dark adaptation in mice. The results demonstrated that, in addition to photoreceptors, other retinal cell types also showed dynamic molecular changes and specifically enriched signaling pathways under light/dark adaptation. Importantly, Müller glial cells (MGs) were identified as hub cells for intercellular interactions, displaying complex cell‒cell communication with other retinal cells. Furthermore, light increased the transcription of the deiodinase Dio2 in MGs, which converted thyroxine (T4) to active triiodothyronine (T3). Subsequently, light increased T3 levels and regulated mitochondrial respiration in retinal cells in response to light conditions. As cones specifically express the thyroid hormone receptor Thrb, they responded to the increase in T3 by adjusting light responsiveness. Loss of the expression of Dio2 specifically in MGs decreased the light responsive ability of cones. These results suggest that retinal cells display global transcriptional changes under light/dark adaptation and that MGs coordinate intercellular communication during light/dark adaptation via thyroid hormone signaling.

Effect of Feeding Formaldehyde Treated Rapeseed Meal on Metabolic Profile of Surti Buffalo Heifers

Present experiment was conducted on Surti buffalo heifers to compare the graded level (0%, 0.25%, 0.50%, and 1% CP) of formaldehyde (HCHO)-treated rapeseed meal (RSM) in compounded concentrate mixture (CCM) on various metabolic indices. A total of twenty Surti buffalo heifers (16-18 months old; 164.68±5.43 kg) were divided into 4 homogeneous groups of 5 individuals each. The CCM was formulated using formaldehyde-treated rapeseed meal (@ 0%, 0.25%, 0.50%, or 1% HCHO-treated RSM CP), damaged wheat, corn grit, cottonseed extract, rice polish (fine), deoiled rice bran, rice flake bran, molasses, urea, calcite powder and common salt. FT-0 group was fed with CCM having untreated RSM, while FT-25, FT-50 and FT-100 groups were fed CCM having 0.25 %, 0.5 % and 1% CP from HCHO treated rapeseed meal. Results revealed non-significant differences in the serum total protein, albumin, globulin, cholesterol, albumin: globulin ratio and aspartate transaminase and alanine transaminase activities among different groups of heifers. However, serum urea concentration decreased (p<0.01) due to increased formaldehyde treated RSM (0, 0.25, 0.5 and 1%) in the CCM. Serum T3 level was found elevated (p<0.05) in the FT-50 and FT-100 groups, which revealed that formaldehyde treatment (@ 0.5 % and 1.0 %) had effectively destroyed the glucosinolate in rapeseed meal. Decreased serum urea and increased T3 levels of FT-50 and FT-100 groups indicated the effectiveness of formaldehyde treatment to protect the rapeseed meal without altering other blood metabolites.

Evaluation of thyroid hormones in liver cirrhosis patients on the basis of child pugh score

Introduction: Cirrhosis is an advanced stage of liver fibrosis that is accompanied by distortion of the hepatic vasculature. It is the histological development of regenerative nodules surrounded by fibrous bands in response to chronic liver injury. Objectives: The study was intended to assess serum Triiodothyronine (T3), Thyroxine (T4) levels and Thyroid Stimulating Hormone (TSH) on the basis of Child Pugh Score in patients with Liver Cirrhosis. Methodology: 100 clinically diagnosed cases of Liver Cirrhosis patients were enrolled for the study. Estimation of Thyroid Hormones were performed. Statistical evaluation was done for analysis of the results. Result: The study documented a significant decrease in T3 levels (P= <0.0001), a non-significant increase in T4 levels (P=0.997) and a slightly significant increase in TSH levels (P=0.034) on the basis of CP Score. Conclusion: The patients with liver cirrhosis have significantly decreased levels of T3 with increased CP Score. The routine liver enzymes like AST, ALT and ALP may be unable to predict the risk of development of liver cirrhosis specially in the early stages. Therefore, screening of serum T3 levels is strongly recommended in patients with early-stage liver diseases like ALD, NAFLD, NASH and CLD.

Toxic-Induced Nonthyroidal Illness Syndrome Induced by Acute Low-Dose Pesticides Exposure-Preliminary In Vivo Study.

Background and Objectives: Conditions such as trauma, burns, sepsis, or acute intoxications have considerable consequences on the endocrine status, causing “sick euthyroid syndrome”. Organophosphate exposure may induce an increase in acetylcholine levels, thus altering the thyroid’s hormonal status. The present study aims to identify the effects of acetylcholinesterase inhibition on thyroid hormones. Material and methods: A prospective experimental study was conducted on twenty Wistar rats. Blood samples were drawn to set baseline values for thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4). Chlorpyrifos 0.1 mg/kg was administered by oral gavage to induce acetyl-cholinesterase inhibition. After exhibiting cholinergic symptoms, blood samples were collected to assess levels of cholinesterase and thyroid hormones using ELISA. Results: Butyrylcholinesterase levels confirmed major inhibition immediately after intoxication compared to the baseline, certifying the intoxication. A significant increase in T4 levels was noted (p = 0.01) both at 2 h and 48 h after administration of organophosphate in sample rats. Similarly, T3 almost doubled its value 2 h after poisoning (4.2 ng/mL versus 2.5 ng/mL at baseline). Surprisingly, TSH displayed acute elevation with an afterward slow descending trend at 48 h (p = 0.1), reaching baseline value. Conclusions: This study demonstrated that cholinesterase inhibition caused major alterations in thyroid hormone levels, which may be characterized by a transient hypothyroidism status with an impact on survival prognosis.

Mediator Subunit MED1 Differentially Modulates Mutant Thyroid Hormone Receptor Intracellular Localization and Intranuclear Mobility

Thyroid hormone receptor (TR) plays a key role in mediating the effect of thyroid hormone (T3) by controlling hundreds of genes important in growth, development and metabolism. The two major subtypes of TR, TRα1 and TRβ1 can either activate or repress transcription of target genes. In the absence of T3, TR interacts with corepressors and represses transcription. After binding T3, TR undergoes a conformational change that releases corepressors and recruits coactivators like Mediator subunit MED1. Mutations in TR lead to Resistance to Thyroid Hormone syndrome (RTH), where the thyroid gland produces enough T3, but the RTH mutants are defective in T3 binding, blocking the conformational change required to recruit coactivators. Our previous research has shown that TR is primarily nuclear localized but shuttles rapidly between the nucleus and cytoplasm and that MED1 knockout decreases the nuclear population of TR and impacts its intranuclear mobility. To investigate the effect of MED1 on mutant TR, we either cotransfected mCherry‐tagged RTH TRα1 mutant (A263V, C392X and P398R) expression plasmids into HeLa cells with GFP‐MED1, or transfected mutant TRs into MED1‐/‐ mouse embryonic fibroblasts. The nuclear/cytoplasmic (N/C) ratio of the RTH TRα1 mutants was measured by comparing the average fluorescence intensity in the nucleus and the cytoplasm. Our data show that MED1 overexpression and knockout did not change the N/C ratio of the C392X and P398R mutants at physiological T3 levels, while MED1 overexpression increased the P398R mutant’s N/C ratio in elevated T3 levels (Figure 1; p<0.05, n=3, 60 cells per replicate). A significantly greater number of cells cotransfected with A263V and MED1 had nuclear or cytoplasmic aggregates compared to wildtype (WT) TR (p<0.05, n=3, ≥60 cells per replicate), while both an increase in T3 levels and MED1 knockout significantly decreased the number of cells with aggregates (p<0.05, n=3, 60 cells per replicate). Similar aggregates were found in cells cotransfected with MED1 and RTH mutant A263S or cancer mutant K74E, A264V, indicating mutations near residue 263 may contribute to aggregation. Cotransfection of A263V and MED13, a Mediator complex subunit that does not interact with TR directly, also resulted in aggregation, indicating that nonspecific interactions may also contribute to aggregate formation. Interestingly, MED1 overexpression significantly increased the intranuclear mobility of A263V TR in fluorescence recovery after photobleaching (FRAP) assays (Figure 2; p<0.05, n=3, 20 nuclei per replicate) suggesting that MED1 interacts with A263V TR at physiological T3 levels. However, MED1 overexpression did not impact the intranuclear mobility of either C392X or P398R TR, indicating that MED1 does not interact with them at physiological T3 levels (p>0.05, n=3, 20 nuclei per replicate). Lastly, results show that MED1 knockout increased the intranuclear mobility of WT but not mutant TRs at physiological T3 levels. Clinical records show a larger number of less severe RTH cases with A263V/S mutations, a smaller number of cases with P398R mutation and both a larger number and more severe cases with C392X mutation. Together these data further our understanding of how the interaction between MED1 and RTH TRα1 mutants may contribute to RTH pathology.

Mild Endurance Exercise during Fasting Increases Gastrocnemius Muscle and Prefrontal Cortex Thyroid Hormone Levels through Differential BHB and BCAA-Mediated BDNF-mTOR Signaling in Rats.

Mild endurance exercise has been shown to compensate for declined muscle quality and may positively affect the brain under conditions of energy restriction. Whether this involves brain-derived neurotrophic factor (BDNF) and mammalian target of rapamycin (mTOR) activation in relation to central and peripheral tissue levels of associated factors such as beta hydroxy butyrate (BHB), branched-chain amino acids (BCAA) and thyroid hormone (T3) has not been studied. Thus, a subset of male Wistar rats housed at thermoneutrality that were fed or fasted was submitted to 30-min-mild treadmill exercise bouts (five in total, twice daily, 15 m/min, 0° inclination) over a period of 66 h. Prefrontal cortex and gastrocnemius muscle BHB, BCAA, and thyroid hormone were measured by LC-MS/MS analysis and were related to BDNF and mammalian target of rapamycin (mTOR) signaling. In gastrocnemius muscle, mild endurance exercise during fasting maintained the fasting-induced elevated BHB levels and BDNF-CREB activity and unlocked the downstream Akt-mTORC1 pathway associated with increased tissue BCAA. Consequently, deiodinase 3 mRNA levels decreased whereas increased phosphorylation of the mTORC2 target FOXO1 was associated with increased deiodinase 2 mRNA levels, accounting for the increased T3 tissue levels. These events were related to increased expression of CREB and T3 target genes beneficial for muscle quality previously observed in this condition. In rat L6 myoblasts, BHB directly induced BDNF transcription and maturation. Mild endurance exercise during fasting did not increase prefrontal cortex BHB levels nor was BDNF activated, whereas increased leucine levels were associated with Akt-independent increased phosphorylation of the mTORC1 target P70S6K. The associated increased T3 levels modulated the expression of known T3-target genes involved in brain tissue maintenance. Our observation that mild endurance exercise modulates BDNF, mTOR and T3 during fasting provides molecular clues to explain the observed beneficial effects of mild endurance exercise in settings of energy restriction.

Exposure of adult zebrafish to androstenedione alters thyroid hormone levels and the transcriptional expression of genes related to the hypothalamus-pituitary-thyroid axis

Androstenedione (AED) is a naturally occurring androgen that is released into the environment through human and animal excretion. Several studies have shown that AED can interfere with the normal growth, development, and reproduction of organisms. However, studies examining the thyroid system, an important part of endocrine system of fish, are still lacking. This study examines thyroid hormone levels including T3 and T4, and transcriptional expression levels of genes associated with the hypothalamic-pituitary-thyroid axis (HPT axis) in adult zebrafish. Fish were exposed to a solvent control and three other concentrations of AED (0.2, 2.3, and 23.7 μg/L) for 60 days. Results indicated that AED significantly increased T4 levels but inhibited transcription of some HPT axis-related genes (nis, tpo, tg, dio1, dio2, sult1 st5, pax8, and nkx2.1) in female zebrafish. The adverse effects of AED on the thyroid system in males were very low, only affecting down-regulation of the tshb gene and up-regulation of the thrb gene. The overall results demonstrated that AED interferes with the thyroid endocrine system in fish.

Prevalence of Sub-Clinical Hypothyroidism in Diagnosed Cases of Gallstone Disease

Thyroid issues have long been debated as a possible cause of gall stone disease. The link between hypothyroidism and gallstone disease could be explained in a variety of ways. The main objective of this study is to determine the prevalence of hypothyroidism in gallstone patients and to rule out hypothyroidism as a probable cause of gallstone formation. A prospective study was conducted in surgical wards of Department of surgery sree balaji medical college from 2016 to 2017. All patients were evaluated using a comprehensive clinical history and examination, as well as suitable investigations such as abdominal USG, thyroid function tests, and lipid profiles. Out of 22 patients 19 patients (86.4%) had normal TSH, 2 patients (9.1%) had increased TSH, 1 patient (4.5%) had decreased TSH. Raised TSH was more in the AGE Group of 61- 75 years, which is comparable to other studies. Out of 22 patients, (100%) had normal T3 levels. 19 patients (86.4%) had normal T4 levels and Ultrasound examination of neck, 2 patients (9.1%) had decreased T4 level and 1 patient (4.5%) had increased T4 levels and 3 patients (13.6%) had abnormal Ultrasound Neck findings. Hence In this Study Cholelithiasis is most commonly seen in Females of age group of 41-60 years and prevalence of raised TSH level in cholelithiasis patient was 9% and most were found in the age group of 61-80 years.

​Evaluation of Various Biochemical Parameters in the Serum and Tissues of Lambs with White Muscle Disease

Background: In this study, the effects of White Muscle Disease (WMD) on certain blood parameters, MDA and GSH levels in liver and thyroid tissues and the thyroid hormones were investigated in sheep. Methods: Sixteen lambs (8 with WMD, 8 controls) of similar age, 3 to 50 days old, selected from the same region were used in the study. Blood samples were taken from all animals. One ml Vitamin E + Se were injected (I/M) to the lambs with WMD and blood and tissue samples were collected after the treatment as well. The serum Ca, P, T3, T4, albumin, globulin, total protein, glutathione (GSH) values were analyzed by an auto-analyzer. Malondialdehyde (MDA) and GSH amounts of the liver and thyroid tissues were also determined. Result: The low Ca ion amount in lambs with WMD was found to have increased after injections of vitamin E + Se. P levels followed the same pattern. Total protein, albumin and globulin levels increased after treatment. It was determined that there was a decrease in T3 levels and an increase in T4 levels in patient lamb sera. The levels of GSH in both the liver and thyroid tissues were found to have decreased and statistical significance (at what level) was only found for the liver GSH levels. MDA levels in the hepatic and thyroid tissues were found to have slightly increased in the WMD group. In conclusion, serum differences in Ca, P, albumin, globulin, total protein, T3, T4, GSH, GSH and MDA levels were statistically significant between the groups.

Effect of Pesticide Indoxacarb on the Thyroid Gland in Swiss Albino Mice

Background and objectives: Pesticides play an essential role in crop protection, but their overuse caused environmental pollution and harmful effect on different animal body systems, including the endocrine system. The thyroid gland is one of the homeostatic regulators of metabolic activities, which is affected by the elements of the external environment. There are very limited studies on the effect of indoxacarb on the histological architecture and functions of thyroid gland. Therefore, this study was conducted with the aim of examining functionally and histologically of the thyroid gland exposed to indoxacarb. Method: 24 Swiss albino mice male and female were randomly divided into two groups, each group male and female; group I is a control group given orally with 1ml of distilled water and group II orally treated with 120 mg/kg Bw. of indoxacarb daily for 3 weeks. Blood samples were collected from each mouse under anesthetic to determine the thyroid-stimulating hormone (TSH), thyroxine (T4) levels. Thyroid gland histopathology was attained for the evaluation of the indoxacarb effect. Results: The treated mice showed non-significant increase in T4 levels and a significant decrease in TSH levels but there was no significant difference recorded in T4 and TSH levels between sexes. Histologically, the sections of the thyroid gland of the treated group showed empty and irregular follicles, degeneration of the follicular epithelial tissue, and hyperplasia in the lining of some follicles, the capsule with congestion blood vessels. Conclusion: This study concluded that indoxacarb may act as a thyroid gland toxicant.

Developmental Toxicity and Thyroid Endocrine Disruption of Polyhexamethylene Guanidine Hydrochloride and Humidifier Disinfectant in Zebrafish Larvae

Polyhexamethylene guanidine (PHMG), a major component of humidifier disinfectants (HDs), is responsible for the outbreak of pulmonary diseases in pregnant women and children in South Korea. This study aims to characterize the developmental toxicity and thyroid endocrine disruption of Vegetable Home Cleanup HD and its main component, PHMG-hydrochloride (PHMG-H), in zebrafish embryo/larvae after a 7-d exposure. Acute lethality, development, whole-body thyroid hormones, and transcription of genes related to the hypothalamus-pituitary-thyroid axis were investigated. Zebrafish embryos exposed to the actual-use concentration (0.6%) of HD exhibited significant embryo coagulation and larval mortality. The concentration of triiodothyronine (T3) was significantly high in fish exposed to 0.4 mg/L PHMG-H, accompanied by the downregulation of the tshβ gene. These results suggest a feedback mechanism for the regulation of increased T3 levels. Significant decrease of thyroxine (T4) concentration, increase of T3/T4 ratio, and upregulation of the deio2 gene in fish exposed to PHMG-H suggested that there was an increase in the active T3 due to the catalysis of outer ring deiodination. Future research is required to determine the factors that contribute to the differences in toxicity between the two counter ions of PHMG.

Effects of the emulsifiable herbicide Dicamba on amphibian tadpoles: an underestimated toxicity risk?

The effects of exposure to the herbicide Dicamba (DIC) on tadpoles of two amphibian species, Scinax nasicus and Elachistocleis bicolor, were assessed. Mortality and biochemical sublethal effects were evaluated using acetylcholinesterase (AChE), glutathione S-transferase (GST), glutathione reductase (GR), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) activities and thyroid hormone (T4) levels. The LC50 value at 48h was 0.859 mg L-1 for S. nasicus and 0.221 mg L-1 for E. bicolor tadpoles. After exposure to sublethal DIC concentrations for 48 h, GST activity increased in S. nasicus but significantly decreased in E. bicolor with respect to controls. GR activity decreased only in S. nasicus at all the tested DIC concentrations. AChE activity was significantly inhibited in both S. nasicus and E. bicolor tadpoles at 48 h. DIC also caused significant changes in transamination, as evidenced by an increase in AST and ALT activities in both amphibian species. T4 levels were higher in DIC-treated tadpoles of both species than in controls. The DIC-induced biochemical alterations in glutathione system enzymes and transaminases indicate lesions in liver tissues and cellular function. Moreover, the observed AChE inhibition could lead to the accumulation of acetylcholine, excessively stimulating postsynaptic receptors, and the increase in T4 levels in both species may indicate an overactive thyroid. The commercial DIC formulation showed a high biotoxicity in the two amphibian native species after short-term exposure, controversially differing from the toxicity level indicated in the official fact sheet data. This fact highlights the need for an urgent re-categorization and reevaluation of DIC toxicity in native species.

Metribuzin-induced non-adverse liver changes result in rodent-specific non-adverse thyroid effects via uridine 5′-diphospho-glucuronosyltransferase (UDPGT, UGT) modulation

Metribuzin is a herbicide that inhibits photosynthesis and has been used for over 40 years. Its main target organ is the liver and to some extent the kidney in rats, dogs, and rabbits.Metribuzin shows a specific thyroxine (T4) profile in rat studies with T4 increases at low doses and T4 decreases at higher doses. Only the T4 decreases occur together with histopathological changes in the thyroid and weight changes of liver and thyroid.A set of experiments was conducted to investigate metribuzin's endocrine disruptor potential according to European guidance and regulations.The results indicate that a liver enzyme modulation, i.e. of the uridine 5′-diphospho-glucuronosyltransferase (UDPGT, UGT), is most likely responsible for both increased and decreased plasma thyroxine level and for thyroid histopathological observations. Animals with high T4 levels show low UGT activity, while animals with low T4 levels show high UGT activity. A causal relationship was inferred, since other potentially human-relevant mode of action (MOA) pathways were excluded in dedicated studies, i.e. inhibition of deiodinases (DIO), inhibition of thyroid peroxidase (TPO) or of the sodium importer system (NIS). This liver metabolism-associated MOA is considered not relevant for human hazard assessment, due to species differences in thyroid homeostasis between humans and rats and, more importantly, based on experimental data showing that metribuzin affects UGT activity in rat but not in human hepatocytes. Further, we discuss whether or not increased T4 levels in the rat, in the absence of histopathological changes, should be considered as adverse and therefore used as an appropriate hazard model for humans.Based on a weight of evidence approach, metribuzin should not be classified as an endocrine disruptor with regard to the thyroid modality.