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1.
Ecotoxicol Environ Saf ; 205: 111338, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32956867

RESUMO

Lead (Pb) is well-recognized for its great hazards to human and wildlife health. It has negative influences on multiple organs and systems of birds. Especially, lead exposure caused adverse impacts on bird reproduction. In this study, one week old female Japanese quails were randomly allocated into four groups and each group was respectively fed with 0, 50 ppm, 500 ppm and 1000 ppm Pb in drinking water for 36 days to determine the effects of chronic lead exposure on ovarian development and function. The results showed that Pb did accumulate in the ovary and ovarian development was delayed by high dose lead exposure (500 ppm and 1000 ppm). Moreover, high Pb dosage induced ovarian histopathological damages characterized by granulosa cells disorganization, follicle atresia and interstitial cell degeneration. Meanwhile, the concentration of estradiol (E2) was significantly decreased and mRNA levels of genes involved with ovarian steroidogenesis were significantly down-regulated by high concentration Pb. In addition, Pb exposure caused increasing cell apoptosis and significant changes of the expression of genes involved with cell death in the ovary. High dose Pb exposure also inhibited thyroid hormone release and disrupted ovarian thyroid deiodination apart from causing thyroid histopathological injury such as follicular deformation and atrophy. The study indicated that Pb might cause ovarian malfunction by inducing ovary and thyroid microstructural damages, thyroid hormone and estrogen release inhibition and ovarian steroidogenesis disruption.


Assuntos
Coturnix/metabolismo , Poluentes Ambientais/toxicidade , Estradiol/metabolismo , Expressão Gênica/efeitos dos fármacos , Chumbo/toxicidade , Ovário/efeitos dos fármacos , Hormônios Tireóideos/metabolismo , Adolescente , Animais , Apoptose/efeitos dos fármacos , Coturnix/genética , Coturnix/crescimento & desenvolvimento , Relação Dose-Resposta a Droga , Poluentes Ambientais/metabolismo , Estradiol/genética , Feminino , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/patologia , Humanos , Chumbo/metabolismo , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/patologia , Ovário/crescimento & desenvolvimento , Ovário/metabolismo , Ovário/patologia , Distribuição Aleatória , Reprodução/efeitos dos fármacos , Reprodução/genética , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Hormônios Tireóideos/genética
2.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 36(3): 250-254, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32981281

RESUMO

Objective: To investigate the potential toxic effects and mechanisms of Tris(1; 3-dichloro-2-propyl) phosphate (TDCIPP) on thyroid in female SD rats.Methods: Thirty-two 3-weeks-old female SD rats were randomly divided into normal group(treated with corn oil ), and low/moderate/high-dose group treated with TDCIPP (dissolved in corn oil )(n=8). All rats were treated with corn oil or TDCIPP (50, 100, 250 mg/(kg·d)) once a day during a 21-day period. All rats were sacrificed after the last administration. Serum thyroid stimulating hormone (TSH), 3,3',5-triiodothyronine (T3), 3,3',5,5'-tetraiodothyronine (T4), free 3,3',5,5'-tetraiodothyronine (FT4) were detected with ELISA kit. Morphology of thyroid was observed with hematoxylin and eosin (HE) staining. Expressions of genes and proteins correlate with thyroid were measured respectively by real-time fluorescence quantitative PCR and Western blot. Results: Compared with control group, morphology of thyroid showed follicles irregular arrangement, hypocolloid, and follicular hyperplasia in TDCIPP treatment groups. The levels of serum TSH in low-dose TDCIPP group and T3 in high-dose TDCIPP group were significantly higher than those in control group(P<0.05). Thyroid stimulating hormone receptor (TSHR) mRNA expression was decreased distinctly in low-dose TDCIPP group, while the expression of thyroperoxidase (TPO) mRNA was increased notably in moderate and high-dose TDCIPP groups(P<0.05,P<0.01). Compared with control group, the level of TRß protein was decreased significantly in moderate and high-dose TDCIPP groups, while the expressions of udp-glucuronosyl-transferases (UGTs) and cytochrome-p450-3A1 (CYP3A1) proteins were upregulated notably in TDCIPP treatment groups(P<0.05). Conclusion: Treated with 50 mg/(kg·d) TDCIPP can cause thyroid hyperplasia, change the levels of thyroid hormones, and disturb thyroid function, therefore, it has toxic effects on the thyroid.


Assuntos
Organofosfatos , Glândula Tireoide , Hormônios Tireóideos , Animais , Feminino , Organofosfatos/toxicidade , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Disgenesia da Tireoide/induzido quimicamente , Glândula Tireoide/efeitos dos fármacos , Hormônios Tireóideos/sangue
3.
Chemosphere ; 260: 127565, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32758781

RESUMO

The effects of fluoride on endocrine tissues has not been sufficiently explored to date. The current body of knowledge suggest significant effects of that mineral on reducing sex hormone levels, which may consequently impair fertility and disrupt puberty. The majority of studies confirm that sodium fluoride increases TSH levels and decreases the concentrations of T3 and T4 produced by the thyroid. Moreover, a correlation was observed between NaF and increased secretion of PTH by the parathyroid glands, without a significant impact on body calcium levels. Probably, fluoride may exert adverse effects on insulin levels, impairing pancreatic function and resulting in abnormal glucose tolerance. Observations also include decreased levels of cortisol secreted by the adrenal glands. In light of the few existing studies, the mechanism of fluoride toxicity on the endocrine system has been described.


Assuntos
Sistema Endócrino/efeitos dos fármacos , Fluoretos/farmacologia , Glândulas Suprarrenais/metabolismo , Animais , Fluoretos/efeitos adversos , Fluoretos/toxicidade , Humanos , Hidrocortisona/metabolismo , Insulina/análise , Glândulas Paratireoides/efeitos dos fármacos , Glândulas Paratireoides/metabolismo , Fluoreto de Sódio/farmacologia , Fluoreto de Sódio/toxicidade , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Hormônios Tireóideos/metabolismo
4.
Aquat Toxicol ; 227: 105608, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32858424

RESUMO

As a feed additive in agriculture, the antibiotic oxytetracycline (OTC) has become widely distributed in the natural environment, leading to the exposure of many organisms to low doses of OTC. Although OTC is clinically contraindicated in children because of its multiple side effects, the effect of exposure to low doses of environmental OTC on children is unknown, particularly during development. In this study, we investigated the effects of OTC on the thyroid endocrine system in zebrafish, through determinations of the whole-body contents of triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) by enzyme-linked immunosorbent assay, and analysis of the mRNA expression of regulatory genes involved in the hypothalamus-pituitary-thyroid (HPT) axis using quantitative real-time polymerase chain reaction. Zebrafish embryos were exposed to OTC at environmentally relevant concentrations from 2 h to 120 days post-fertilisation. After exposure to OTC at 1,000 and 5,000 ng/L, T3 contents were significantly enhanced (37.8% and 45.1%, respectively) and TSH contents were reduced (16% and 16.3%, respectively) compared with those in the controls. The OTC-driven increase in the transcription of genes involved in thyroid synthesis (tpo and nis) may be responsible for the altered T3 levels. These data indicate that OTC may cause thyroid dysfunction and lead to reduced TSH secretion owing to enhanced negative feedback control of the HPT axis. Meanwhile, a decrease in body length, weight, and BMI and an increase in heart rate were observed with increasing OTC exposure. In conclusion, our results indicate that long-term exposure to low concentrations of OTC may alter the transcription of key genes involved in the HPT axis, as well as T3 and TSH contents, thereby disrupting the thyroid system and affecting the growth and development of zebrafish.


Assuntos
Oxitetraciclina/toxicidade , Glândula Tireoide/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/fisiologia , Animais , Disruptores Endócrinos/toxicidade , Tireotropina , Tiroxina/metabolismo , Tri-Iodotironina/metabolismo
5.
Aquat Toxicol ; 225: 105547, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32623180

RESUMO

Some chemicals in the environment disrupt thyroid hormone (TH) systems leading to alterations in organism development, but their effect mechanisms are poorly understood. In fish, this has been limited by a lack of fundamental knowledge on thyroid gene ontogeny and tissue expression in early life stages. Here we established detailed expression profiles for a suite of genes in the hypothalamic-pituitary-thyroid (HPT) axis of zebrafish (Danio rerio) between 24-120 h post fertilisation (hpf) and quantified their responses following exposure to 3,3',5-triiodo-L-thyronine (T3) using whole mount in situ hybridisation (WISH) and qRT-PCR (using whole-body extracts). All of the selected genes in the HPT axis demonstrated dynamic transcript expression profiles across the developmental stages examined. The expression of thyroid receptor alpha (thraa) was observed in the brain, gastrointestinal tract, craniofacial tissues and pectoral fins, while thyroid receptor beta (thrb) expression occurred in the brain, otic vesicles, liver and lower jaw. The TH deiodinases (dio1, dio2 and dio3b) were expressed in the liver, pronephric ducts and brain and the patterns differed depending on life stage. Both dio1 and dio2 were also expressed in the intestinal bulb (96-120 hpf), and dio2 expression occurred also in the pituitary (48-120 hpf). Exposure of zebrafish embryo-larvae to T3 (30 and 100 µg L-1) for periods of 48, 96 or 120 hpf resulted in the up-regulation of thraa, thrb, dio3b, thyroid follicle synthesis proteins (pax8) and corticotropin-releasing hormone (crhb) and down-regulation of dio1, dio2, glucuronidation enzymes (ugt1ab) and thyroid stimulating hormone (tshb) (assessed via qRT-PCR) and responses differed across life stage and tissues. T3 induced thraa expression in the pineal gland, pectoral fins, brain, somites, gastrointestinal tract, craniofacial tissues, liver and pronephric ducts. T3 enhanced thrb expression in the brain, jaw cartilage and intestine, while thrb expression was suppressed in the liver. T3 exposure suppressed the transcript levels of dio1 and dio2 in the liver, brain, gastrointestinal tract and craniofacial tissues, while dio2 signalling was also suppressed in the pituitary gland. Dio3b expression was induced by T3 exposure in the jaw cartilage, pectoral fins and brain. The involvement of THs in the development of numerous body tissues and the responsiveness of these tissues to T3 in zebrafish highlights their potential vulnerability to exposure to environmental thyroid-disrupting chemicals.


Assuntos
Tri-Iodotironina/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Hormônio Liberador da Corticotropina , Hipotálamo/efeitos dos fármacos , Larva/efeitos dos fármacos , Hipófise/efeitos dos fármacos , Glândula Tireoide/efeitos dos fármacos , Hormônios Tireóideos/metabolismo , Tironinas/metabolismo , Tironinas/farmacologia , Tireotropina , Peixe-Zebra/fisiologia , Proteínas de Peixe-Zebra/genética
6.
Nat Commun ; 11(1): 3614, 2020 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-32681015

RESUMO

Larval metamorphosis and recruitment represent critical life-history transitions for most teleost fishes. While the detrimental effects of anthropogenic stressors on the behavior and survival of recruiting fishes are well-documented, the physiological mechanisms that underpin these patterns remain unclear. Here, we use pharmacological treatments to highlight the role that thyroid hormones (TH) play in sensory development and determining anti-predator responses in metamorphosing convict surgeonfish, Acanthurus triostegus. We then show that high doses of a physical stressor (increased temperature of +3 °C) and a chemical stressor (the pesticide chlorpyrifos at 30 µg L-1) induced similar defects by decreasing fish TH levels and affecting their sensory development. Stressor-exposed fish experienced higher predation; however, their ability to avoid predation improved when they received supplemental TH. Our results highlight that two different anthropogenic stressors can affect critical developmental and ecological transitions via the same physiological pathway. This finding provides a unifying mechanism to explain past results and underlines the profound threat anthropogenic stressors pose to fish communities.


Assuntos
Peixes/crescimento & desenvolvimento , Larva/crescimento & desenvolvimento , Praguicidas/toxicidade , Glândula Tireoide/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Clorpirifos/toxicidade , Poluição Ambiental/efeitos adversos , Metamorfose Biológica/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Glândula Tireoide/metabolismo , Hormônios Tireóideos/metabolismo
7.
Clin Nucl Med ; 45(9): 719-721, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32657858

RESUMO

We report a case of a 66-year-old woman with small cell lung cancer (stage IIB, T2N1M0), who received immunotherapy with nivolumab monthly for 2 months and then presented with thyrotoxic symptoms associated with suppressed thyroid-stimulating hormone levels and elevated free thyroid hormone levels, although previous thyrotropin performed 1 month ago was normal. Thyroid uptake and scan demonstrated diffusely decreased uptake in both thyroid lobes. The 4-hour percentage uptake was 0.7%, and the 24-hour percentage uptake was 0.3%. This was followed by development of hypothyroidism within few weeks. Findings suggested drug-induced thyroiditis secondary to nivolumab therapy.


Assuntos
Imunoterapia/efeitos adversos , Medicina Nuclear , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/fisiopatologia , Idoso , Feminino , Humanos , Neoplasias Pulmonares/terapia , Nivolumabe/efeitos adversos , Carcinoma de Pequenas Células do Pulmão/terapia , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/metabolismo , Tireotropina/metabolismo , Tiroxina/metabolismo
8.
Toxicol Lett ; 331: 143-151, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32525014

RESUMO

Although organotin compounds are known to disturb thyroid signaling and antioxidant defense system, the sex-differences underlying these effects of triphenyltin chloride (TPT) in fish remain unclear. To understand these differences, adult zebrafish (Danio rerio) were exposed to different concentrations of TPT (0, 10, 100, or 1000 ng/L) for 28 days. Female zebrafish exposed to TPT showed significantly increased thyroxine (T4) content and decrease triiodothyronine (T3) content, possibly due to downregulation of deiodinase (dio2) and uridine diphosphate glucuronosyl transferase (ugt1ab). However, decreased T4 and T3 contents in male zebrafish accompanied with upregulation of dio1, dio2 and ugt1ab. TPT exposure can lead to sex-specific thyroid disruption in adult zebrafish via alterations the Hypothalamus-pituitary-thyroid-liver axis. In addition, the gene expression levels of metabolizing enzymes, such as cyp1b, cyp1c, gpx1a, or sult1st1 were also to vary in a sex-dependent manner in adult zebrafish liver. Downregulation of cyp19a and cyp19b and decreased 17ß-estradiol (E2) contents were detected in both female and male zebrafish. Therefore, a sex-specific of thyroid disruption response after TPT exposure was observed in adult zebrafish, possibly due to inherent in female or males detoxifying enzyme capacities.


Assuntos
Disruptores Endócrinos/toxicidade , Compostos Orgânicos de Estanho/toxicidade , Caracteres Sexuais , Glândula Tireoide/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Proteínas de Peixe-Zebra , Peixe-Zebra/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Relação Dose-Resposta a Droga , Feminino , Expressão Gênica/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Glândula Tireoide/metabolismo , Hormônios Tireóideos/genética , Hormônios Tireóideos/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
9.
PLoS One ; 15(5): e0233596, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32469958

RESUMO

BACKGROUND: Although reversible in some patients, primary hypothyroidism is considered a permanent condition requiring lifelong hormone therapy. This study aimed to investigate the factors predicting the successful discontinuation of levothyroxine (L-T4) therapy in patients with primary hypothyroidism. METHODS: A retrospective study was performed in primary hypothyroidism patients who met inclusion criteria: patients who maintained stable L-T4 therapy for more than 1 year, following gradual dose reduction of L-T4 based on the clinical decision (L-T4 tapering); patients receiving either no L-T4 or a fixed minimum dose for more than 1 year after L-T4 tapering. Reduction in L-T4 dosage by 12.5-50 µg within 3 months was considered as L-T4 tapering. Serum free T4, TSH, and clinical symptoms were evaluated before, during and after tapering. Logistic regression and decision tree analyses were performed to predict the successful discontinuation of L-T4. RESULTS: Among 382 patients, 22.5% and 58.4% showed successful discontinuation (T4-Discontinued) and dose reduction (T4-Reduced) of L-T4 therapy, while other did not obtained any reduction of L-T4 dose (T4-Unchanged). The median number of tapering visit was 1.0 (range, 1.0-4.0). In T4-Discontinued group, the TSH level and the positive rate of anti-thyroperoxidase at the time of L-T4 initiation were lower, the duration of L-T4 therapy was shorter, and the maintenance dose of L-T4 at the time of tapering was lower than those in the T4-Unchanged group. In ultrasonography, normal parenchyma was preserved in the T4-Discontinued group while others showed higher rates of heterogeneous or hypoechoic parenchymal changes. Among those different characteristics, the longer duration of L-T4 therapy and the higher maintenance dose of L-T4 at the time of tapering significantly predicted the failure of discontinuation of L-T4 in multivariate analysis. A decision tree showed that patients with a duration of L-T4 therapy >4.6 years had lower success rate of discontinuation. CONCLUSION: Shorter duration of L-T4 therapy and lower L-T4 dose at the time of tapering are the predictable factors for successful L-T4 tapering in stably maintained primary hypothyroidism patients.


Assuntos
Hipotireoidismo/tratamento farmacológico , Tiroxina/uso terapêutico , Adulto , Idoso , Feminino , Terapia de Reposição Hormonal , Humanos , Hipotireoidismo/sangue , Hipotireoidismo/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/efeitos dos fármacos , Resultado do Tratamento , Ultrassonografia
10.
Artigo em Inglês | MEDLINE | ID: mdl-32468518

RESUMO

Bifenthrin (BF) and acetochlor (AT) are widely used as an insecticide and herbicide, respectively, which are introduced to the aquatic environment as a natural result. Although the thyroid active substances may coexist in the environment, their joint effects on fish have not been identified. We examined the joint toxicity of BF and AT in zebrafish (Danio rerio) in this study. An acute lethal toxicity test indicated that the median lethal concentration (LC50) values of BF and AT under 96 h treatment were 0.40 and 4.56 µmol L-1, respectively. The binary mixture of BF + AT displayed an antagonistic effect on the acute lethal toxicity. After 14 days post fertilization (dpf) with exposure to individual pesticides at sub-lethal concentrations of, no effects were observed on the catalase (CAT) and peroxidase (POD) activities, while the binary mixtures (except for the 7.2 × 10-3 µmol L-1 BF + 1.2 × 10-2 µmol L-1 AT exposure group) significantly induced the CAT activity. The superoxide dismutase (SOD) activity and triiodothyronine (T3) level were significantly increased in all exposure groups. The thyroxine (T4) level remained unchanged after exposure to individual pesticides, but significantly increased in the 7.2 × 10-3 µmol L-1 BF + 1.2 × 10-2 µmol L-1 AT group. The expressions of the genes Dio2, TRa, TSHß and CRH in the thyroid hormone (TH) axis were significantly up-regulated in the 7.2 × 10-3 µmol L-1 BF + 0.4 × 10-2 µmol L-1 AT group. Our data indicated that the binary mixture of BF + AT significantly altered the antioxidant enzyme activities and gene expressions in the hypothalamic-pituitary-thyroid (HPT) axis and changed the TH levels.


Assuntos
Herbicidas/toxicidade , Piretrinas/toxicidade , Hormônios Tireóideos/metabolismo , Toluidinas/toxicidade , Peixe-Zebra/fisiologia , Animais , Embrião não Mamífero/efeitos dos fármacos , Glândula Tireoide/efeitos dos fármacos , Hormônios Tireóideos/genética , Testes de Toxicidade Aguda
11.
Chemosphere ; 256: 127066, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32434091

RESUMO

Tri(1,3-dichloropropyl) phosphate (TDCPP) potentially damages the thyroid system in humans and animals. However, knowledge of its toxic effects and underlying mechanisms is limited. The present study was conducted to determine the thyroid hormone-disrupting effects of TDCPP and its major metabolite, bis(1,3-dichloro-2-propyl) phosphate (BDCPP) in rat pituitary cell lines (GH3). TDCPP and BDCPP, that mimic the thyroid hormone (TH), promoted GH3 cell proliferation and modulated the progression of the cell cycle at 20 and 200 µmol/L, respectively. Similar to T3, TDCPP and BDCPP also significantly upregulated c-fos and downregulated Tshß gene expression. Although the binding affinity of these chemicals for thyroid receptor ß (TRß) was not measured, significant competition between these chemicals to bind to the membrane thyroid hormone receptor (integrin αvß3) was found, suggesting that TDCPP and BDCPP were strongly bound to integrin αvß3. Results from a molecular docking analysis provided further evidence of strong binding affinities of TDCPP and BDCPP for integrin αvß3, and the ligand binding site of Arg-Gly-Asp (RGD) was identified. Real-time PCR also supported the supposition that, after binding to integrin αvß3, TDCPP and BDCPP may induce the activation of the extracellular signal-regulated protein kinase (ERK1/2) signal transduction pathway. Taken together, our data suggest that TDCPP and BDCPP have the ability to mimic THs and that the underlying mechanism might be associated with their interactions with integrin αvß3 and the activation of the ERK1/2 pathway, providing new insight into the mechanism of TDCPP- and BDCPP-induced cytotoxicity.


Assuntos
Organofosfatos/toxicidade , Hormônios Tireóideos/metabolismo , Testes de Toxicidade , Animais , Proliferação de Células/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Integrina alfaVbeta3/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteína Quinase 3 Ativada por Mitógeno , Simulação de Acoplamento Molecular , Oligopeptídeos , Organofosfatos/metabolismo , Compostos Organofosforados , Ratos , Transdução de Sinais , Glândula Tireoide/efeitos dos fármacos
12.
J Surg Res ; 253: 272-279, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32402852

RESUMO

BACKGROUND: Mechanical ventilation (MV) is life saving; yet it may induce severe lung injury and lead to multisystem organ failure and death. Thyroid hormones (THs) promote alveolar fluid clearance and alleviates hypoxia-induced lung injury. Given that the mechanism involved in hypoxia-induced lung injury is different from that of ventilator-induced lung injury, we examined the effects of thyroid function on lung extravascular fluid (LF), aquaporin 5 (AQP 5) expression, and alveolar viscoelasticity (AVE) in mechanically ventilated rat. METHODS: Hypothyroid (hypo) and hyperthyroid (hyper) animals were generated by administration of metimazole and L-thyroxine, respectively. Lung injury was induced by high-tidal volume MV. The LF was estimated by lung wet weight-to-dry weight ratio assessment. Expression of AQP 5 was evaluated by western blotting and in situ immunohistochemistry. The AVE was judged by elastic lung pressure/volume curve recording. RESULTS: Injurious MV significantly reduced lung AQP 5 expression and altered LF and AVE in a thyroid function-dependent manner. Regardless of animals' ventilation mode, hyper state caused significant reductions in LF and lung AQP 5 protein. It also improved AVE irrespective of animals' ventilation mode. The effects of hypo condition on LF, AQP 5 expression, and AVE were in contrast to that of hyper state. CONCLUSIONS: These data indicate that thyroid function has profound effects on LF, AQP 5, and AVE in mechanically ventilated lungs. Given that the effects of thyroidal status were as prominent as that of injurious MV, we suggest that thyroid function should be considered when patients are to be subjected to MV.


Assuntos
Alvéolos Pulmonares/fisiopatologia , Respiração Artificial/efeitos adversos , Glândula Tireoide/metabolismo , Hormônios Tireóideos/metabolismo , Lesão Pulmonar Induzida por Ventilação Mecânica/metabolismo , Animais , Antitireóideos/administração & dosagem , Aquaporina 5/análise , Aquaporina 5/metabolismo , Modelos Animais de Doenças , Elasticidade , Humanos , Masculino , Metimazol/administração & dosagem , Ratos , Glândula Tireoide/efeitos dos fármacos , Tiroxina/administração & dosagem , Volume de Ventilação Pulmonar , Lesão Pulmonar Induzida por Ventilação Mecânica/etiologia , Lesão Pulmonar Induzida por Ventilação Mecânica/fisiopatologia , Viscosidade
13.
Crit Rev Oncol Hematol ; 150: 102950, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32339980

RESUMO

Incidence and mortality of thyroid cancer are increasing, thus making mandatory to improve the knowledge of disease etiology. The hypothesis of a role for anthropogenic chemicals is raising wide consideration. A series of occupational studies revealed that job exposures with high risk of chemical contamination were usually more prone to thyroid cancer development. These include shoe manufacture, preserving industry, building activities, pulp/papermaker industry and the wood processing, agricultural activities, and other work categories characterized by contact with chemicals, such as chemists and pharmacists. However, such epidemiological analyses cannot define a causal relationship. Thyroid-disrupting activity has emerged for a broad set of anthropogenic chemicals, with the best evidence being gained for polychlorinated biphenyls, polybrominated diphenyl ethers, dioxins, bisphenols, phthalates, pesticides, and heavy metals. A series of case-control studies, assessing exposure to thyroid-disrupting agents, as measured on biological matrices, have been recently performed providing the following insights: a) positive relationship with thyroid cancer was found for phthalates, bisphenols, the heavy metals cadmium, copper, and lead; b) polybrominated diphenyl ethers exposure showed no relationship with thyroid cancer c) controversial results were reported for polychlorinated biphenyls and pesticides. However, such studies cannot demonstrate the causal link with disease occurrence, as exposure is assessed after tumour development. Studies with different methodological approach are therefore required for defining the role of anthropogenic environmental chemicals in thyroid carcinogenesis.


Assuntos
Dioxinas/efeitos adversos , Poluentes Ambientais/efeitos adversos , Praguicidas/efeitos adversos , Bifenil Polibromatos/efeitos adversos , Bifenilos Policlorados/efeitos adversos , Glândula Tireoide/efeitos dos fármacos , Neoplasias da Glândula Tireoide/induzido quimicamente , Monitoramento Ambiental , Poluentes Ambientais/metabolismo , Éteres Difenil Halogenados , Humanos , Praguicidas/metabolismo , Fenóis/toxicidade , Éteres Fenílicos/efeitos adversos , Glândula Tireoide/fisiologia
14.
Ecotoxicol Environ Saf ; 196: 110544, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32251951

RESUMO

Thiazole-Zn is a systemic fungicide synthesized and developed in China that has been used for the prevention and treatment of bacterial and fungal diseases on fruits and vegetables. Thiazole-Zn is a new thyroid disruptor chemical. The purpose of this study was to clarify the thyroid-disrupting property of thiazole-Zn and the mechanism responsible for thyroid hormone (TH) biosynthesis inhibition in male rats induced by thiazole-Zn. First, the effects of different thiazole-Zn doses and exposure times on the thyroid weights, thyroid morphology and serum hormone levels of rats were investigated. The results showed that thiazole-Zn increased thyroid weights and serum thyroid-stimulating hormone (TSH) levels and induced thyroid cell hypertrophy and hyperplasia in a dose-related and time-related manner. Furthermore, measurement of thyroid radioiodine uptake in vivo in rats confirmed that thiazole-Zn inhibited active iodide uptake into the thyroid, which reduced circulating levels of serum T3 and T4. Decreases in circulating THs resulted in a compensatory increase in serum TSH levels through a negative feedback system. Subsequently, sustained excessive stimulation of the thyroid gland by TSH led to thyroid follicular cell hypertrophy and hyperplasia. In addition, thiazole-Zn increased sodium/iodide symporter (NIS) expression in the rat thyroid, and the increased NIS expression promoted and restored iodide uptake into the thyroids of rats. The risk of iodine intake inhibition by thiazole-Zn to humans, especially susceptible individuals, such as children and pregnant women, warrants additional attention.


Assuntos
Complexos de Coordenação/toxicidade , Fungicidas Industriais/toxicidade , Tiadiazóis/toxicidade , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/patologia , Animais , China , Hiperplasia , Hipertrofia , Iodo/metabolismo , Radioisótopos do Iodo , Masculino , Ratos , Ratos Sprague-Dawley , Simportadores/metabolismo , Glândula Tireoide/metabolismo , Hormônios Tireóideos/sangue , Tireotropina/sangue
15.
Artigo em Inglês | MEDLINE | ID: mdl-32294918

RESUMO

Bisphenols (BPs), and especially bisphenol A (BPA), are known endocrine disruptors (EDCs), capable of interfering with estrogen and androgen activities, as well as being suspected of other health outcomes. Given the crucial role of thyroid hormones and the increasing incidence of thyroid carcinoma in the last few decades, this review analyzes the effects of BPS on the thyroid, considering original research in vitro, in vivo, and in humans published from January 2000 to October 2019. Both in vitro and in vivo studies reported the ability of BPs to disrupt thyroid function through multiple mechanisms. The antagonism with thyroid receptors (TRs), which affects TR-mediated transcriptional activity, the direct action of BPs on gene expression at the thyroid and the pituitary level, the competitive binding with thyroid transport proteins, and the induction of toxicity in several cell lines are likely the main mechanisms leading to thyroid dysfunction. In humans, results are more contradictory, though some evidence suggests the potential of BPs in increasing the risk of thyroid nodules. A standardized methodology in toxicological studies and prospective epidemiological studies with individual exposure assessments are warranted to evaluate the pathophysiology resulting in the damage and to establish the temporal relationship between markers of exposure and long-term effects.


Assuntos
Compostos Benzidrílicos , Disruptores Endócrinos , Fenóis , Doenças da Glândula Tireoide , Glândula Tireoide , Adolescente , Adulto , Idoso , Animais , Compostos Benzidrílicos/toxicidade , Cesárea , Criança , Pré-Escolar , Estudos Transversais , Disruptores Endócrinos/toxicidade , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Camundongos , Pessoa de Meia-Idade , Fenóis/toxicidade , Gravidez , Estudos Prospectivos , Ratos , Ovinos , Doenças da Glândula Tireoide/induzido quimicamente , Glândula Tireoide/efeitos dos fármacos , Adulto Jovem
16.
Environ Res ; 183: 109280, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32311913

RESUMO

BACKGROUND: In animal studies, perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters thyroid homoeostasis and thyroid hormone concentrations; epidemiologic evidence is limited. OBJECTIVES: We aimed to determine the association of prenatal exposure to TCDD with thyroid hormone concentrations in the Seveso Second Generation Study, a unique cohort of children born to TCDD-exposed women resulting from a 1976 chemical factory explosion in Seveso, Italy. METHODS: We included 570 children (288 female, 282 male) with complete follow-up data, including a fasting blood draw. Serum levels of total and free thyroxine (T4), free triiodothyronine (T3), and thyroid stimulating hormone (TSH) were measured using immunoassays. We defined prenatal TCDD exposure as: 1) maternal initial TCDD concentration measured in serum collected soon after the explosion and 2) maternal TCDD estimated at pregnancy. RESULTS: Compared to the lowest quartile (Q1), maternal initial serum TCDD was associated with lower free T3 (Q2: adj-ß = -0.13, 95%CI -0.26, 0.00; Q3: adj-ß = -0.22, 95%CI -0.35, -0.09; Q4: adj-ß = -0.14, 95%CI -0.28, 0.00; p-trend = 0.02). In participants with high thyroid antibody status, inverse associations between maternal initial serum TCDD and free T3 were significantly stronger than in participants with normal antibody status (p-interaction = 0.02). We also observed a positive association between maternal initial serum TCDD and TSH concentrations in participants with high thyroid antibody status (Q2: adj-ß = 11.4%, 95%CI -25.2, 66.1; Q3: adj-ß = 49.0%, 95%CI 3.0, 115.5; Q4: adj-ß = 105.5, 95%CI 36.6, 209.2; p-trend < 0.01) but not in those participants with normal antibody status (p-interaction < 0.01). Similar results were found for TCDD estimated at pregnancy. DISCUSSION: Our results suggest prenatal exposure to TCDD, a potent endocrine-disrupting compound, may alter thyroid function later in life. Populations with additional thyroid stress may be particularly susceptible to in utero exposure of thyroid disrupting chemicals.


Assuntos
Dioxinas , Efeitos Tardios da Exposição Pré-Natal , Glândula Tireoide , Hormônios Tireóideos , Animais , Anticorpos , Criança , Dioxinas/toxicidade , Feminino , Humanos , Itália , Masculino , Dibenzodioxinas Policloradas , Gravidez , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/imunologia , Glândula Tireoide/fisiopatologia , Hormônios Tireóideos/metabolismo
17.
Aquat Toxicol ; 222: 105466, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32172180

RESUMO

The co-occurrence of hypoxia and xenobiotics is extremely common in natural environments, highlighting the necessity to elicit their interaction on aquatic toxicities. In the present study, marine medaka embryos were exposed to various concentrations (nominal 0, 1, 3.3 and 10 mg/L) of perfluorobutane sulfonate (PFBS), an environmental pollutant of emerging concern, under either normoxia (6.9 mg/L) or hypoxia (1.7 mg/L) condition. After acute exposure till 15 days post-fertilization, single or combined toxicities of PFBS and hypoxia on embryonic development (e.g., mortality, hatching and heartbeat) and endocrine systems were investigated. Sex and thyroid hormones were measured by enzyme-linked immunosorbent assay. Transcriptional changes of endocrine genes were determined by quantitative real-time PCR assays. Co-exposure to 10 mg/L PFBS and hypoxia caused a further reduction in survival rate and heart beat compared to single exposure. PFBS induced a precocious hatching, while no larvae hatched under hypoxia condition. By disturbing the balance of sex hormones, either PFBS or hypoxia single exposure produced an anti-estrogenic activity in medaka larvae. However, PFBS and hypoxia combinations reversed to estrogenic activity in co-exposed larvae. Variation in disrupting pattern may be attributed to the interactive effects on steroidogenic pathway involving diverse cytochrome P450 enzymes. Regarding thyroid system, PFBS exposure caused detriments of multiple processes along thyroidal axis (e.g., feedback regulation, synthesis and transport of thyroid hormones, receptor-mediated signaling and thyroid gland development), while hypoxia potently impaired the development and function of thyroid gland. Combinations of PFBS and hypoxia interacted to dysregulate the function of thyroid endocrine system. In summary, the present study revealed the dynamic interaction of PFBS pollutant and hypoxia on aquatic developmental toxicities and endocrine disruption. Considering the frequent co-occurrence of xenobiotics and hypoxia, current results would be beneficial to improve our understanding about their interactive mechanisms and provide baseline evidences for accurate ecological risk evaluation.


Assuntos
Embrião não Mamífero/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Fluorcarbonetos/toxicidade , Hipóxia/metabolismo , Oryzias/metabolismo , Ácidos Sulfônicos/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Embrião não Mamífero/metabolismo , Desenvolvimento Embrionário/fisiologia , Feminino , Hormônios Esteroides Gonadais/metabolismo , Larva/efeitos dos fármacos , Larva/metabolismo , Masculino , Oryzias/crescimento & desenvolvimento , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/embriologia , Glândula Tireoide/metabolismo , Hormônios Tireóideos/metabolismo
18.
Chemosphere ; 249: 126536, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32217413

RESUMO

This study investigated the influences of titanium dioxide nanoparticles (n-TiO2) on the thyroid endocrine disruption and neurobehavioral defects induced by pentachlorophenol (PCP) in zebrafish (Danio rerio). Embryos (2 h post-fertilization) were exposed to PCP (0, 3, 10, and 30 µg/L) or in combination with n-TiO2 (0.1 mg/L) until 6 days post-fertilization. The results showed that n-TiO2 alone did not affect thyroid hormones levels or transcriptions of related genes. Exposure to PCP significantly decreased thyroid hormone thyroxine (T4) content, thyroid stimulating hormone (TSH) level and transcription of thyroglobulin (tg), but significantly increased 3,5,3'-triiodothyronine (T3) level and upregulation of deiodinase 2 (dio2). In comparison, the co-exposure with n-TiO2 significantly reduced the content of T3 by depressing the potential targets, tg and dio2. For neurotoxicity, the single and co-exposure resulted in similar effects with significant downregulation of neurodevelopment-related genes (ELAV like RNA Binding Protein 3, elavl3; Growth associated protein-43, gap43; α-tubulin) and inhibited locomotor activity. The results indicated that the presence of n-TiO2 significantly enhanced the PCP-induced thyroid endocrine disruption but not the neurobehavioral defects in zebrafish larvae.


Assuntos
Disruptores Endócrinos/toxicidade , Pentaclorofenol/toxicidade , Peixe-Zebra/fisiologia , Animais , Sistema Endócrino/efeitos dos fármacos , Larva/efeitos dos fármacos , Nanopartículas/toxicidade , Pentaclorofenol/metabolismo , Glândula Tireoide/efeitos dos fármacos , Hormônios Tireóideos/metabolismo , Titânio/toxicidade , Tri-Iodotironina/metabolismo , Peixe-Zebra/metabolismo
19.
Toxicol Appl Pharmacol ; 394: 114957, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32173372

RESUMO

The adverse effects of triphenyltin (TPT) on aquatic systems have attracted much attention because TPT is widely used and prevalent in aquatic environments. Here, zebrafish embryos/larvae were exposed to TPT (0, 0.039, 0.39, and 3.9 nM; 0, 15, 150 and 1500 ng/L) for 7 or 14 days to determine its toxic effects on the hypothalamic-pituitary-thyroid (HPT) axis. The results showed that whole-body total T4 and T3 levels were significantly decreased, which was accompanied by the significant upregulation of the expression of the dio1, dio2 and ugt1ab genes after exposure to TPT for 7 and 14 days. Genes related to thyroid hormone synthesis (crh, tshß, nis, tpo and tg) were upregulated at both 7 and 14 days after TPT exposure. This might have been due to the positive feedback regulation of the HPT axis, which is caused by a decrease in thyroid hormone in the whole body in zebrafish. In addition, the survival rates and body lengths were reduced after treatment with TPT for 7 and 14 days. This indicated that TPT caused adverse effect on the development of zebrafish embryos/larvae. In summary, the results suggested that TPT caused thyroid disruption and developmental toxicity in zebrafish larvae.


Assuntos
Desenvolvimento Embrionário/efeitos dos fármacos , Larva/efeitos dos fármacos , Compostos Orgânicos de Estanho/toxicidade , Doenças da Glândula Tireoide/induzido quimicamente , Peixe-Zebra , Animais , Disruptores Endócrinos/toxicidade , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Crescimento/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Metamorfose Biológica/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Análise de Sobrevida , Glândula Tireoide/efeitos dos fármacos , Tiroxina/metabolismo , Tri-Iodotironina/metabolismo , Poluentes Químicos da Água/toxicidade
20.
Toxicology ; 436: 152412, 2020 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-32145347

RESUMO

We investigated the effects of Kalach 360 SL (KL), Glyphosate (G)-based herbicide, on bone tissue in different groups of female Wistar rats. Group 1 (n = 6) received a standard diet and served as a control, groups 2 and 3 (n = 6 each) received 0.07 ml (D1: 126 mg/Kg) and 0.175 ml (D2: 315 mg/Kg) of KL dissolved in the water for 60 days. The plasma was used to examine the metabolic balance markers (calcium, phosphorus, phosphatase alkaline (PAL), and vitamin D (vit D) and hormonal status (oestrogen and thyroid hormones). As a result, sub-chronic exposure to KL induced a perturbation of bone metabolism (calcium and phosphorus) and hormonal status disturbance. The histological and immunohistochemical study of the thyroid gland revealed a disturbance in morphological structure and thyroid cells function. Moreover, the KL disrupting eff ;ect on thyroid function was investigated by measuring changes in plasma levels of thyroid hormones. Free triiodothyronine (FT3) and thyroxine (FT4) were decreased in female rats breast-fed from rats treated with D and D2 of KL. This eff ;ect was associated with an increase in the plasma level of thyroid-stimulating hormone (TSH). Thus, that KL leads to hypothyroidism. Decrease in levels of oestrogen and thyroid dysfunction led to a disruption in the skeletal bone. The histological study and SEM in bone results allowed us to observe, in rats exposed to KL, the thinning and discontinuity of bone trabecular with a significant decrease in the number of nodes (intertrabecular links).In conclusion, KL sub-chronic exposure caused an aspect of osteoporosis.


Assuntos
Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Fêmur/efeitos dos fármacos , Glicina/análogos & derivados , Herbicidas/toxicidade , Animais , Biomarcadores/sangue , Estrogênios/sangue , Feminino , Fêmur/metabolismo , Fêmur/ultraestrutura , Glicina/toxicidade , Hipotireoidismo/sangue , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/patologia , Osteoporose/sangue , Osteoporose/induzido quimicamente , Osteoporose/patologia , Ratos Wistar , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Hormônios Tireóideos/sangue
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