Reduction In T4 Research Articles

Protective effect of platelet-rich plasma against structural and functional changes of the adult rat testis in carbimazole-induced hypothyroidism.

Hypothyroidism (HT) influences spermatogenesis and is associated with male infertility. Platelet-rich plasma (PRP), a biological product rich in growth factors, promotes tissue repair. In this study, the likely protective effects of PRP on testicular tissue damage in carbimazole (CBZ)-induced HT were evaluated. Forty male rats were divided into four groups. HT was induced by administering CBZ (1.35 mg/kg orally, for 45 days). Two doses of PRP (40 μL each, locally injected into the testis on days 15 and 30) were also given. After 45 days, blood samples were taken from the heart to measure triiodothyronine (T3), thyroxine (T4), and testosterone levels, and semen analysis was performed. For stereological assessment, the left testis was removed, fixed, embedded, sectioned, and stained with hematoxylin and eosin. The right testis was excised to evaluate antioxidant levels. CBZ was demonstrated to induce HT, characterized by significant reductions in T3 and T4. HT was associated with decreased testicular weight, impaired sperm parameters, reduced testosterone concentration, diminished antioxidant activity, reduced volumes of testicular components, and lower total numbers of testicular cells of various types. When HT samples were treated with PRP, improvement was observed for all of these changes. This protective effect could be attributed to the growth factors present in PRP. PRP appears to prevent the structural changes in the testes and the deterioration in sperm quality caused by CBZ-induced HT. This protective effect is likely due to mitigation of oxidative damage and elevation of testosterone levels.

Bypassing the brain barriers: upregulation of serum miR-495 and miR-543-3p reflects thyroid-mediated developmental neurotoxicity in the rat.

Evaluating the neurodevelopmental effects of thyroid-disrupting chemicals is challenging. Although some standardized developmental and reproductive toxicity studies recommend serum thyroxine (T4) measures in developing rats, extrapolating between a serum T4 reduction and neurodevelopmental outcomes is not straightforward. Previously, we showed that the blood-brain and blood-cerebrospinal fluid barriers may be affected by developmental hypothyroidism in newborn rats. Here, we hypothesized that if the brain barriers were functionally disturbed by abnormal thyroid action, then small molecules may escape from the brain tissue and into general circulation. These small molecules could then be identified in blood samples, serving as a direct readout of thyroid-mediated developmental neurotoxicity. To address these hypotheses, pregnant rats were exposed to propylthiouracil (PTU, 0 or 3 ppm) to induce thyroid hormone insufficiency, and dams were permitted to give birth. PTU significantly reduced serum T4 in postnatal offspring. Consistent with our hypothesis, we show that tight junctions of the brain barriers were abnormal in PTU-exposed pups, and the blood-brain barrier exhibited increased permeability. Next, we performed serum microRNA Sequencing (miRNA-Seq) to identify noncoding RNAs that may reflect these neurodevelopmental disturbances. Of the differentially expressed miRNAs identified, 7 were upregulated in PTU-exposed pups. Validation by qRT-PCR shows that miR-495 and miR-543-3p were similarly upregulated in males and females. Interestingly, these miRNAs have been linked to cell junction dysfunction in other models, paralleling the identified abnormalities in the rat brain. Taken together, these data show that miR-495 and miR-543-3p may be novel in vivo biomarkers of thyroid-mediated developmental neurotoxicity.

Thyroid function and opium use disorder: a cross-sectional study on the Fasa adults cohort study (FACS), 2017

BackgroundAddiction increases the risk of different lifelong disorders. However, there are limited studies evaluating the effects of opioid use disorder (OUD) on thyroid function. The present study aimed to compare the thyroid function of individuals with and without OUD.MethodsThis cross-sectional study was conducted on 700 eligible participants of the Persian Cohort of Fasa, Iran. Pregnant women and participants with false or missing data were excluded from the study. Remained participants were divided into case and control groups based on the recorded history of OUD. Frozen plasma samples of the cohort bank were used to determine the levels of T3, T4, and thyroid-stimulating hormone (TSH). The thyroid function was compared between the two groups using the Mann-Whitney test (P < 0.05).ResultsThe mean age of the final studied population (n = 648) was 54.0 ± 9.8 years, including 336 men (49.1%) and 197 participants with OUD (28.8%). The median levels of TSH, T4, and T3 were 2.91 ± 4.61, 9.26 ± 3.65, and 1.22 ± 0.49, respectively. The case group had significantly higher TSH (3.72 ± 6.2 vs. 2.58 ± 3.75, P < 0.001) and lower T4 (8 ± 3.6 vs. 9.8 ± 3.5, P < 0.001). Also, T3 was slightly lower in the case group (1.1 ± 0.5 vs. 1.3 ± 0.5; P = 0.369), although this association was only significant in female opium users (P < 0.001).ConclusionsThe present findings revealed that OUD caused a reduction in T4 while increasing TSH. Therefore, OUD may lead to the development of primary hypothyroidism, which needs to be investigated in future studies.

The Impact of Metformin on the Development of Hypothyroidism and Cardiotoxicity Induced by Cyclophosphamide, Methotrexate, and Fluorouracil in Rats.

Cyclophosphamide (CYP), methotrexate (MTX), and 5-fluorouracil (5-FU) are extensively utilized in the therapeutic management of various malignancies. It is noteworthy, however, that potential chemotherapy-related complications include the occurrence of hypothyroidism and cardiotoxicity. Metformin (MET) is a pharmacological agent for managing type 2 diabetes. It has been reported to mitigate certain toxic manifestations associated with chemotherapy. This study's primary objective is to investigate MET's protective effects against hypothyroidism and cardiotoxicity induced by CMF treatment. A total of forty male rats were allocated into four distinct groups, each consisting of ten rats per group. These groups were categorized as follows: saline, MET, CMF, and CMF + MET. The experimental group of rats were administered CMF via intraperitoneal injection, receiving two doses of CMF, and fed MET in their daily drinking water, with a 2.5 mg/mL concentration. Blood samples were collected into EDTA tubes for assessment of TSH, free and total (T4 and T3), troponin I, CK, and CK-MB levels utilizing Electrochemiluminescence Immunoassays (ECI). The saline and MET groups did not exhibit significant alterations in thyroid hormones or cardiotoxic biomarkers. In contrast, in the CMF group, there was a notable reduction in T4, FT4, T3, and FT3 levels but no significant changes in TSH levels; however, troponin I, CK, and CK-MB levels were notably elevated. MET co-treatment with CMF did not ameliorate these effects caused by CMF. In conclusion, CMF treatment induced hypothyroidism and cardiotoxicity in rats, but MET co-treatment did not rescue the reduction of thyroid hormones or the elevation of cardiotoxic biomarkers.

Exogenous corticosterone administration during pregnancy in mice alters placental and fetal thyroid hormone availability in females

IntroductionMaternal prenatal psychological stress is associated with adverse pregnancy outcomes and increased risk of adverse health outcomes in children. While the molecular mechanisms that govern these associations has not been fully teased apart, stress-induced changes in placental function can drive sex-specific phenotypes in offspring. We sought to identify and examine molecular pathways in the placenta that are altered in response to maternal prenatal stress. MethodsWe previously employed a mouse model of maternal prenatal stress where pregnant dams were treated with stress hormone (CORT) beginning in mid-gestation. Using this model, we conducted RNAseq analysis of whole placenta at E18.5. We used qRT-PCR to validate gene expression changes in the placenta and in a trophoblast cell line. ELISAs were used to measure the abundance of thyroid hormones in maternal and fetal serum and in the placenta. ResultsDio2 was amongst the top differentially expressed genes in response to exogenous stress hormone. Dio2 expression was more downregulated in placenta of female fetuses from CORT-treated dams than both control placenta from females and placenta from male fetuses. Consistent with Dio2's role in production of bioactive thyroid hormone (T3), we found that there was a reduction of T3 in placenta and serum of female embryos from CORT-treated dams at E18.5. Both T3 and T4 were reduced in the fetal compartment of the placenta of female fetuses from CORT-treated dams at E16.5. Exogenous stress hormone induced reduction in thyroid hormone in females was independent of circulating levels of TH in the dams. DiscussionThe placental thyroid hormone synthesis pathway may be a target of elevated maternal stress hormone and modulate fetal programming of health and disease of offspring in a sex-specific fashion.

Longitudinal Findings on the Oneiric Activity Changes Across the Pandemic.

COVID-19 pandemic waves have strongly influenced individuals' behaviors and mental health. Here, we analyzed longitudinal data collected in the Spring 2020 and 2021 from a large Italian sample with the aim of assessing changes in dream features between the first and third wave. Specifically, we evaluated the modifications of pandemic dream activity as a function of the general distress variations over time. Also, we detected the best explanatory variables of nightmare frequency and distress. Participants previously involved in the web survey during the first wave of the pandemic were asked to complete a new online survey on sleep and dream features available in Spring 2021 (N=728). Subjects decreasing their level of psychological general distress in the third (T3) vs the first (T1) pandemic wave were defined as "Improved" (N=330). In contrast, participants with an unchanged or increased level of general distress were defined as "Not Improved" (N=398). Statistical comparisons revealed that dream recall frequency, nightmare frequency, lucid dream frequency, and emotional intensity show a reduction in T3 than T1. Moreover, the Improved group is characterized by lower nightmare rate and nightmare distress than Not Improved people. Our findings confirmed that beyond the trait-like variables (ie, age, sex), specific sleep-related measures are related to nightmare features. In particular, poor sleep hygiene was one of the best determinants of nightmare distress among Not Improved subjects. Our findings revealed that people experienced an adaptation to the pandemic during the third wave. We also strengthen the notion that nightmares and their variations over time are strongly related to human well-being, suggesting that specific trait-like and sleep-related factors could modulate the relationship between mental health and nightmare features.

Documented and projected actions in vitro of thyroid hormone as L -thyroxine (T4) on basal cell carcinoma of the skin

Thyroid hormone as L-thyroxine (T4) at physiological concentrations acts at its cell surface receptor on integrin avb3 to stimulate cancer cell proliferation1. These proliferation studies have been conducted in vitro, but pharmacological reduction of T4 and substitution of nuclear receptor ligand 3,3’,5-triiodo-L-thyronine (T3) is a state of euthyroid hypothyroxinemia that has been shown clinically to arrest tumor growth in patients with cancer. T3 is inactive at physiological levels at the plasma membrane integrin receptor. A preclinical study of human basal cell carcinoma (BCC) cells has shown that the integrin thyroid hormone receptor regulates BCC radiosensitivity. While the large majority of BCCs are very manageable clinically, a small number of such tumors are aggressive. In this review of documented and proposed effects of T4 on BCC cells, we raise the possibility that BCC aggressiveness reflects T4 actions on its thyrointegrin target. The functions affected by T4 at the integrin in other human cancers include enhanced cell proliferation, anti-apoptosis, immune checkpoint regulation and metastasis, as well as state of radiosensitivity. The importance of investigating this possible pathophysiology is that euthyroid hypothyroxinemia may be tested as a treatment option.

Long-term effect of a large dose of iodinated contrast in patients with mild thyroid dysfunction: a prospective cohort study.

More than 75 million procedures with intravascular iodine-based contrast media (ICM) are performed worldwide every year, and some patients undergoing these procedures do not have normal thyroid function. The long-term effects of ICM in patients with mild thyroid dysfunction (TD) are unclear. This prospective cohort study was conducted in China. Patients with stable angina pectoris with total triiodothyronine (TT3) reduction, normal thyroid-stimulating hormone, and reverse triiodothyronine (rT3) were enrolled and divided into high-dose (≥100 mL ICM) and low-dose groups (<100 mL ICM). We dynamically investigated the trends in thyroid function, rT3, and thyroid antibodies 1 year after ICM exposure. A total of 154 patients completed 6 months of follow-up and 149 completed 1 year of follow-up. Thyroglobulin antibody (TGAB) levels were elevated in 41 (26.6%) patients before ICM exposure, 11 (7.1%) of whom also had elevated thyroid peroxidase antibody levels. Transient subclinical TD occurred 6 months after ICM exposure; 75.5% of post-operative TD occurred in the high-dose group. One patient developed severe hypothyroidism with myxedema, requiring drug intervention 1 year after ICM exposure. The level of rT3 showed no statistically significant changes during post-operative follow-up (P = 0.848). The TGAB level decreased at 6th month (P < 0.001), but increased at 1 year after ICM exposure (P = 0.002). Patients with T3 reduction are at risk of transient subclinical TD and hypothyroidism after a single large dose of ICM. Follow-up of this population at 9-12 months after ICM exposure is warranted.

Assessment of thyroid function tests in patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD), a group of diseases of distinct aetio-pathological consideration with different phenotypic presentations where smoking is the leading cause, all share the ultimate result of airflow limitation. This study aimed to evaluate thyroid function tests (TFT) in patients with COPD. Pulmonary function tests (PFT) were performed for 30 patients with obstructive lung disease and fifteen healthy control individuals. We measured SPO2 to confirm COPD and assess the severity of the disease and assessed TT3, TT4, and TSH using the ELISA test. The values of VC, FVC, and FEV in the first second and PEF, TSH, and SPO2 were lower in the COPD group than in the control group (P-value=0.001). In severe COPD (FEV1<50%), there was a significant reduction in T3 but not T4 or TSH compared to mild-moderate COPD patients. Thyroid dysfunction was observed in patients with COPD pointing to a metabolic response; patients with lower weight indices had a lower TSH and, consequently, T3.

Measurement of paraoxonase-1, visfatin levels in Iraqi diabetic and diabetic with hypothyroidism

Introduction and Aim: This study is to evaluate the levels of paraoxonase-1 and visfatin in diabetic and diabetic with hypothyroidism patients and to discover the relationship of paraoxonase-1 and visfatin levels in these patients. Materials and Methods: The study included 35 subjects in control group (G1), 35 with diabetes (G2), and 35 diabetes with hypothyroidism (G3), aged ranging 25-50 years for all the study groups and BMI with (20.5-25.4) Kg/m2. Serum and whole blood were used for estimating F.B.S., HbA1c%, lipid profile, T4, TSH, paraoxonase-1 and visfatin. Results: The results revealed a significant elevation in F.B.S., HbA1c%, TC, TG, VLDL and LDL in G2 and G3 compared to G1. The HDL levels showed a significant decrease in G2, G3 compared to G1. Also, showed significant reduction in T4 in G3 compared to G2 and G1. A significant elevation in TSH in G3 compared to G2 and G1 and a significant decrease in paraoxonase-1 but increase in visfatin for G3 more than G2 when compared to G1 were observed. Conclusion: The study concluded that paraoxonase -1 and visfatin are suggestive reliable markers for the diagnosis of thyroid disorder in diabetics with hypothyroidism depending on their relation with T4 and TSH.

Subacute and low-dose tributyltin exposure disturbs the mammalian hypothalamus-pituitary-thyroid axis in a sex-dependent manner

Tributyltin (TBT) is an endocrine disruptor chemical (EDC) capable of altering the proper function of the hypothalamus-pituitary thyroid (HPT) axis. This study aimed to evaluate the subacute effects of TBT on the HPT axis of male and female rats. A dose of 100 ng/kg/day TBT was used in both sexes over a 15-day period, and the morphophysiology and gene expression of the HPT axis were assessed. TBT exposure increased the body weight in both sexes, while food efficiency increased - only in male rats. It was also possible to note alterations in the thyroid, with the presence of a stratified epithelium, cystic degeneration, and increased interstitial collagen deposition. A reduction in T3 and T4 levels was only observed in TBT male rats. A reduction in TSH levels was observed in TBT female rats. Evaluating mRNA expression, we observed a decrease in hepatic D1 and TRH mRNA levels in TBT female rats. An increase in D2 mRNA expression in the hypothalamus was observed in TBT male rats. Additionally, no significant changes in TRH or hepatic D1 mRNA expression in TBT male rats or in hypothalamic D1 and D2 mRNA expression in TBT female rats were observed. Thus, we can conclude that TBT has different toxicological effects on male and female rats by altering thyroid gland morphophysiology, leading to abnormal HPT axis function, and even at subacute and low doses, it may be involved in complex endocrine and metabolic disorders.

Screening for Hypothyroidism in children with severe acute malnutrition at Nutrition Rehabilitation Center, Children’s Hospital and Institute of Child Health Multan.

Objective: To determine the percentage of Hypothyroidism in children with severe acute malnutrition. Study Design: Cross Sectional study. Setting: Nutrition Rehabilitation Center, Children’s Hospital and Institute of Child Health Multan. Period: January 2019 to December 2019. Material &amp; Methods: A total of 255 malnourished patients (as per inclusion criteria) were included in current study. A written Performa was designed to collect history, anthropometric measurements and systemic examination. Taking aseptic measures venous blood was sent for baseline tests as well as for T3, T4 and TSH, total serum protein albumin and total ferritin levels to hospital laboratory. Correlation between serum thyroid concentrations and total protein, albumin, hemoglobin and serum ferritin were estimated by using t-test and p-vlaue less than 0.05 was considered as significant. Total collected data was entered and analyzed in SPSS version 21.0. Results: A total of 255 malnourished children were included in this study. Majority of studied subjects were male (52.5%) with 83.92%, 3-5 years of age. Amongst the 255 children mean values of T3 in MAM and SAM patients were 105.4 ng/dl and 89.7 ng/dl respectively. There was a statistically significant (p &lt;0.001) association between decreased T3 and type of malnutrition. Similarly, mean values of T4 in MAM and SAM patients were 6.3 ug/dl and 5.7 ug/dl respectively that was statistically significant (p &lt;0.05). Lower values of T4 were higher among SAM children in 1 to 3 years age group compared to respective MAM children with p value .0.05 and high T4 value in 3-5 years age group of MAM children were both statistically insignificant. Higher mean Values of TSH was found in SAM compared to MAM children both age groups. Conclusion: Severe acute malnutrition (SAM) is associated with reduction in T3 and T4 levels and higher levels of TSH in SAM children as compared to MAM. The altered thyroid hormone status in children with PEM is perhaps a protective phenomenon to limit protein catabolism and lower energy requirements.

Investigating the protective role of metformin on lithium-induced hypothyroidism.

Induction of oxidative stress events has been shown to be associated with lithium (Li) hypothyroidism induction. Metformin (MET) is a commonly used antidiabetic drug with multiple properties including antiproliferative activity, antioxidant potency, and is usedin polycystic ovarian syndrome treatment. Here, in this study, we aimed to investigate the effect of different doses of MET on Li-induced hypothyroidism for elucidating its mechanism of action. The obtained results demonstrated the oxidative stress reduction in thyroid tissues upon MET treatment. Besides this, the biochemical analysis revealed a significant reduction in T3 and TSH levels (down to 2 ng/ml and 0.05 µU/ml, respectively) in coordination with an observable reduction in T4 level (up to 2.1 ng/ml). Also, a significant reduction in Li-related tissue damages including changes in the morphology and the size of follicles, rate of vascularity, detachment of follicular cells, inflammatory cells infiltration, and follicular cells hypertrophy and disruption was observed. Ultimately, regarding the significant improvement in thyroid tissues and valuable antioxidant activity determined in tissues treated with MET, it is concluded that MET co-administration with Li can significantly reduce the negative effects of Li and enhance the efficacy of Li therapy.

Thyroid Hormones in the Human Body: A review

Thyroid gland is an essential endocrine gland that is present in the human body. This review highlights the production, regulation and disease conditions of the thyroid hormones. The thyroid gland is controlled with the help of hypothalamus and the pituitary gland that is present in the brain. The production of thyroid hormones involves five main steps such synthesis of thyroglobulin (TG), iodide uptake, iodination of thyroglobulin, storage and release. The two important hormones produced by the thyroid gland are Thyroxine (T4) and Triiodothyronine(T3). These two hormones are iodine containing derivatives. Deficiency of iodine in the body results in the reduction of T3 and T4 production. Excess and deficiency of these two hormones result in the major diseases like Hyper and Hypothyroidism. The synthetic forms of Thyroxine(T4) and Triiodothyronine(T3) used in the Pharmaceutical field are Levothyroxine and Liothyronine. Women are most commonly prone to these thyroid diseases comparatively to men. Undiagnosed disease conditions may become fatal. Levothyroxine therapy is commonly used for thyroidism which is a similar synthetic thyroid hormone. Also natural thyroid hormones that are obtained from the dried thyroid glands of animals are available. Thyroid function test and the measurement of T3, T4 plasma level becomes essential for the identification and regular maintenance of thyroid hormones in the body and human well-being.&#x0D;

Thyroid Disruptors: Extrathyroidal Sites of Chemical Action and Neurodevelopmental Outcome-An Examination Using Triclosan and Perfluorohexane Sulfonate.

Many xenobiotics are identified as potential thyroid disruptors due to their action to reduce circulating levels of thyroid hormone, most notably thyroxine (T4). Developmental neurotoxicity is a primary concern for thyroid disrupting chemicals yet correlating the impact of chemically induced changes in serum T4 to perturbed brain development remains elusive. A number of thyroid-specific neurodevelopmental assays have been proposed, based largely on the model thyroid hormone synthesis inhibitor propylthiouracil (PTU). This study examined whether thyroid disrupting chemicals acting distinct from synthesis inhibition would result in the same alterations in brain as expected with PTU. The perfluoroalkyl substance perfluorohexane sulfonate (50 mg/kg/day) and the antimicrobial Triclosan (300 mg/kg/day) were administered to pregnant rats from gestational day 6 to postnatal day (PN) 21, and a number of PTU-defined assays for neurotoxicity evaluated. Both chemicals reduced serum T4 but did not increase thyroid stimulating hormone. Both chemicals increased expression of hepatic metabolism genes, while thyroid hormone-responsive genes in the liver, thyroid gland, and brain were largely unchanged. Brain tissue T4 was reduced in newborns, but despite persistent T4 reductions in serum, had recovered in the PN6 pup brain. Neither treatment resulted in a low dose PTU-like phenotype in either brain morphology or neurobehavior, raising questions for the interpretation of serum biomarkers in regulatory toxicology. They further suggest that reliance on serum hormones as prescriptive of specific neurodevelopmental outcomes may be too simplistic and to understand thyroid-mediated neurotoxicity we must expand our thinking beyond that which follows thyroid hormone synthesis inhibition.

Study the Protective Effect of Ginger against the Toxicity of Dimethoate on Hormones in Rabbits

Organophosphorus insecticides have been widely classified as a health dangerous and high toxicity compounds due to their widespread use and release into the environment. Ginger (Zingiber officinale) has been used as a medicinal plant since antiquity and is known to play diverse biological roles including anti oxidation, anti-inflammation, hyperlipidemia, anti-carcinogenesis, anti-nausea, anti-thrombosis, and antibacterial process. The purpose of these experiments was to study decreasing the toxicity effect of Dimethoate by ginger. All animals in this study were assigned to one of four treatment groups: 0 mg ginger and 0 mg dimethoate /kg BW (control); 100 mg ginger/kg BW; 43.2 mg dimethoate /kg BW; and 43.2 mg dimethoate plus 100 mg ginger/kg BW. Rabbits were orally managed the particular measurements each other day for 12 weeks. Results indicated that treatment with ginger alone caused significant (P&lt;0.05) increase in body weight (BW) and relative weight of testes compared to control animals. Whereas the rabbits treated with dimethoate showed significant (P&lt;0.05) decrease in BW and relative weight of testes compared with control. Results showed that treatment with DM caused significant (P&lt;0.05) decrease activity of testosterone, T3 and T4. While, increase the levels of FSH and LH in plasma. Ginger caused significant (P&lt;0.05) increase in the activity of testosterone, T3 and T4 in plasma compared to control. While, decrease the levels of FSH and LH in plasma. The presence of ginger with DM caused significant (P&lt;0.05) decrease in the reduction of T3 and T4, while caused an improvement in the levels of testosterone as compared to control and the presence of ginger with DM caused increase in the levels of FSH and LH as compared to control, and this means that ginger counteracted the toxic effects of DM.

Thyroid Pathological Consequences Induced by Caffeine in Female Rats

Objective: this study was designed to investigate the histopathological changes induced by caffeine onthyroid, liver and kidneys in female rats. Caffeine is a central nervous stimulant of methyl xanthine class ofdrugs, it has many hormonal and metabolic effects.Method: twenty-four adult female rats was split in to four equal categories of 6 rats in each group as thefollowing: Group1,control group received distilled water only by oral gavage. Group2, received 35mg\kg ofcaffeine solution. Group3, received 75mg\kg of caffeine and Group4, received 150mg\kg of caffeine. Theexperiment continued for 40 days. After 24 hours of the end of experiment, the animals were sacrificed andblood has been withdrawn from vena cava to prepare serum for hormonal analysis, whereas liver, kidneysand thyroid were excised and fixed in formalin solution for histopathological processing.Results: caffeine ingestion cause significant reduction in thyroid function (reduction in T3, T4 and TSH)in all treated groups compared to control group in addition histopathological study show enlargement ofthyroid follicle with thinning of lining epithelium of acini, vacuolation of both renal tubules, hepatocytesand vascular congestion of these organs.Conclusion: Caffeine consumption in high doses causes many histologic and hormonal effects in the studiedorgans.

Reproductive and developmental toxicity screening study of an acetone extract of rosemary

In 2017, JECFA requested reproductive and developmental toxicity studies to finalize an acceptable daily intake for solvent rosemary extracts. Thus, an OECD 421 reproductive/developmental toxicity study was conducted using an acetone rosemary extract that complied with JECFA and EFSA food additive specifications. Rosemary extract was provided to rats at dietary concentrations of 0 (control), 2100, 3600, or 5000 mg/kg, for 14 days before mating, during mating, and thereafter (throughout gestation and up to Lactation Day 13 for females) until necropsy. General toxicity (clinical signs, body weight, food consumption) and reproductive/developmental outcomes (fertility and mating performance, estrous cycles, anogenital distance, thyroid hormones, reproductive organ weights, thyroid histopathology) were assessed. There were no signs of general toxicity and no effects on reproduction; thus, the highest concentration tested (equivalent to mean daily intakes of 316 or 401 mg/kg bw/day [149 or 189 mg/kg bw/day carnosol and carnosic acid] for males and females, respectively) was established as the no-observed-adverse-effect level for general and reproductive toxicity. Dose-related reductions in T4 were observed for Day 13 pups (not seen on Day 4) but were not accompanied by any histopathological changes in the thyroid; further investigations are required to determine the biological relevance of these T4 reductions.

Liothyronine could block the programmed death-ligand 1 (PDL1) activity: an e-Pharmacophore modeling and virtual screening study

Purpose The interaction between PD-L1 on tumor cells and the programmed death 1 (PD1) on immune cells helps them to escape the immune system elimination. Therefore, developing therapeutic agents to block this interaction has garnered a lot of attention as a therapeutic approach. In the present study, we have tried to screen for an inhibitory compound to inhibit the interaction between the PD1/PD-L1 molecules. Methods In this regard, the structure of PD-L1 and its inhibitor were prepared and employed to generate an e-Pharmacophore model. A library of approved compounds was prepared and toxicity analysis using Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) predictor was performed. The built e-Pharmacophore model was validated and used to screen the prepared compound library. Ligand docking and binding energy calculation were performed on the screened ligands. Results A seven-feature e-Pharmacophore model was generated using the PD-L1 complex. All of the compounds within the library passed the ADMET criteria. Performing the virtual screening, only 79 compounds have survived the criteria to fit four pharmacophoric features. The compound with the highest binding energy was the liothyronine (T3). Conclusion The ability of T3 in PD1/PD-L1 checkpoint blockade along with its potential in T4 reduction could be a desirable combination in cancer treatment. These abilities of T3 could be used to restore the ability of the immune system to eliminate tumor cells.

Iodine Deficiency Increases Fat Contribution to Energy Expenditure in Male Mice.

More than a billion people worldwide are at risk of iodine deficiency (ID), with well-known consequences for development of the central nervous system. Furthermore, ID has also been associated with dyslipidemia and obesity in humans. To further understand the metabolic consequences of ID, here we kept 8-week-old C57/Bl6 mice at thermoneutrality (~28°C) while feeding them on a low iodine diet (LID). When compared with mice kept on control diet (LID + 0.71 μg/g iodine), the LID mice exhibited marked reduction in T4 and elevated plasma TSH, without changes in plasma T3 levels. LID mice grew normally, and had normal oxygen consumption, ambulatory activity, and heart expression of T3-responsive gene, confirming systemic euthyroidism. However, LID mice exhibited ~5% lower respiratory quotient (RQ), which reflected a ~2.3-fold higher contribution of fat to energy expenditure. LID mice also presented increased circulating levels of nonesterified fatty acids, ~60% smaller fat depots, and increased hepatic glycogen content, all indicative of accelerated lipolysis. LID mice responded much less to forced mobilization of energy substrates (50% food restriction for 3 days or starvation during 36 hours) because of limited size of the adipose depots. A 4-day treatment with T4 restored plasma T4 and TSH levels in LID mice and normalized RQ. We conclude that ID accelerates lipolysis and fatty acid oxidation, without affecting systemic thyroid hormone signaling. It is conceivable that the elevated plasma TSH levels trigger these changes by directly activating lipolysis in the adipose tissues.