RESUMEN
The 'ethylene glycol ethers' (EGE) are a broad family of solvents and hydraulic fluids produced through the reaction of ethylene oxide and a monoalcohol. Certain EGE derived from methanol and ethanol are well known to cause toxicity to the testes and fetotoxicity and that this is caused by the common metabolites methoxy and ethoxyacetic acid, respectively. There have been numerous published claims that EGE fall into the category of 'endocrine disruptors' often without substantiated evidence. This review systematically evaluates all of the available and relevant in vitro and in vivo data across this family of substances using an approach based around the EFSA/ECHA 2018 guidance for the identification of endocrine disruptors. The conclusion reached is that there is no significant evidence to show that EGE target any endocrine organs or perturb endocrine pathways and that any toxicity that is seen occurs by non-endocrine modes of action.
Asunto(s)
Éteres de Etila/química , Éteres de Etila/farmacología , Óxido de Etileno/química , Óxido de Etileno/farmacología , Animales , Relación Dosis-Respuesta a Droga , Glándulas Endocrinas/efectos de los fármacos , Ambiente , Éteres de Etila/farmacocinética , Óxido de Etileno/farmacocinética , Hormonas Esteroides Gonadales/metabolismo , Humanos , Receptores de Estrógenos/efectos de los fármacos , Absorción Cutánea/fisiologíaRESUMEN
OBJECTIVES: To determine whether feeding CircuCare to rats improves blood circulation, metabolism, immune regulation, endocrine activity, and oxidative stress. METHODS: 28 eight-week-old male Sprague-Dawley rats were evenly randomized into control and experimental groups. The control group was fed with ordinary drinking water, while the experimental group was fed with CircuCare at a daily dose of 93.75 mg per 300 g of body weight over eight weeks. Both groups were subjected to a swimming test, and blood samples were taken to observe any variations in various biochemical parameters before and after the test. Key Findings. The experimental group's mean swimming exhaustion duration was 53.2% longer and had a significantly higher lactic acid removal ratio. Their mean prostaglandin E2 level and mean glucose, cortisol, and glutathione level (30 minutes after swimming test) were also significantly higher. No undesirable impacts from CircuCare relating to general blood biochemistry values and bone mineral density were reported. CONCLUSIONS: The present results show that CircuCare can be safely used to increase stamina and exercise capability, expedite the metabolism of lactic acid, accelerate muscle repair, and promote the antioxidant activity of cells in rats.
Asunto(s)
Circulación Sanguínea/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Metabolismo/efectos de los fármacos , Animales , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Densidad Ósea/efectos de los fármacos , Carica/química , Biología Computacional , Medicamentos Herbarios Chinos/química , Glándulas Endocrinas/efectos de los fármacos , Glándulas Endocrinas/fisiología , Inmunidad/efectos de los fármacos , Ácido Láctico/sangre , Masculino , Modelos Animales , Estrés Oxidativo/efectos de los fármacos , Panax/química , Esfuerzo Físico/efectos de los fármacos , Ratas , Ratas Sprague-DawleyRESUMEN
The mammary gland (MG) and female prostate are plastic reproductive organs which are highly responsive to hormones. Thus, endocrine disruptors, such as bisphenol A (BPA) and exogenous estrogens, negatively affect glandular homeostasis. In addition to previously described alterations, changes in inflammatory markers expression also trigger the development of a microenvironment that contributes to tumor progression. The current work aimed to evaluate the inflammatory responses of the MG and prostate gland to BPA (50 µg/kg) and 17-ß estradiol (35 µg/kg) exposure during the perinatal window of susceptibility. The results showed that at 6 months of age there was an increase in the number of phospho-STAT3 (P-STAT3) positive cells in the female prostate from animals perinatally exposed to 50 µg/kg BPA daily. In addition, the number of macrophages increased in these animals in comparison with nonexposed animals, as shown by the F4/80 marker. Despite an increase in the incidence of lobuloalveolar and intraductal hyperplasia, the MG did not show any difference in the expression of the four inflammatory markers evaluated: tumor necrosis factor-α, COX-2, P-STAT3, and F4/80. Analysis of both glands from the same animal led to the conclusion that exposure to endocrine disruptors during the perinatal window of susceptibility leads to different inflammatory responses in different reproductive organs. As the prostate is more susceptible to these inflammatory mechanisms, it is reasonable to affirm that possible neoplastic alterations in this organ are related to changes in the inflammatory pattern of the stroma, a characteristic that is not evident in the MG.
Asunto(s)
Disruptores Endocrinos/farmacología , Glándulas Endocrinas/efectos de los fármacos , Glándulas Mamarias Animales/metabolismo , Animales , Animales Recién Nacidos/metabolismo , Compuestos de Bencidrilo/farmacología , Disruptores Endocrinos/metabolismo , Glándulas Endocrinas/metabolismo , Estradiol/farmacología , Femenino , Genitales Femeninos/efectos de los fármacos , Genitales Femeninos/metabolismo , Gerbillinae , Humanos , Inflamación/metabolismo , Glándulas Mamarias Animales/efectos de los fármacos , Fenoles/farmacología , Embarazo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Factor de Transcripción STAT3/efectos de los fármacos , Factor de Transcripción STAT3/metabolismo , Esteroides/farmacologíaRESUMEN
Introducción: el propóleo y sus componentes influyen en el metabolismo lipídico; sin embargo, se desconoce su efecto sobre la composición corporal y el metabolismo mineral. Objetivos: determinar el efecto de la suplementación de la dieta con propóleo natural sobre la composición corporal, el metabolismo basal y mineral, y la función endocrina del tejido adiposo. Material y métodos: veinte ratas albinas Wistar macho (8 semanas) se dividieron en dos grupos de 10 animales cada uno. Las ratas fueron alimentadas con dos tipos diferentes de dietas durante 90 días: una dieta estándar para el grupo de control (grupo C) y la misma dieta estándar + un 2 % de propóleo (grupo P). Se determinaron las hormonas tiroideas, la grelina, la leptina, la adiponectina y la insulina, los ácidos grasos no esterificados (AGNE) en el plasma, la composición corporal (masa magra, masa grasa y agua corporal) y el depósito de minerales en órganos diana (bazo, cerebro, corazón, pulmones, testículos, riñones y fémur). Resultados: los niveles plasmáticos de hormona estimulante del tiroides (TSH), triyodotironina (T3) y tiroxina (T4) no mostraron diferencias tras la ingesta del suplemento de propóleo, mientras que los de grelina y adiponectina disminuyeron (p < 0,01 y p < 0,05, respectivamente) y los de insulina (p < 0,01), leptina (p < 0,05) y AGNE (p < 0,05) aumentaron cuando la dieta se suplementó con propóleo al 2 %. Se redujeron el peso y la grasa corporal (p < 0,05), incrementándose la masa magra. Por último, el suplemento de propóleo mejoró el depósito de calcio en el bazo, los pulmones, los testículos y el fémur (p < 0,05). (AU)
Introduction: propolis and its components influence lipid metabolism; however, its effect on body composition and mineral metabolism remains unknown. Objectives: to determine the effect of natural propolis supplementation on body composition, mineral metabolism, and the endocrine function of adipose tissue. Material and methods: twenty albino male Wistar rats (8 weeks old) were divided into two groups of 10 animals each. The rats were fed two different types of diet for 90 days: a standard diet for the control group (group C) and the same standard diet + 2 % propolis (group P). Thyroid hormones, ghrelin, leptin, adiponectin and insulin, non-esterified fatty acids (NEFA) in plasma, body composition (lean mass, fat mass and body water), and mineral deposition in target organs (spleen, brain, heart, lungs, testicles, kidneys and femur) were assessed. Results: thyroid stimulating hormone (TSH), triiodothyronine (T3) and thyroxine (T4) did not show any differences after supplementation with propolis, while ghrelin and adiponectin decreased (p < 0.01 and p < 0.05, respectively) and insulin (p < 0.01), leptin (p < 0.05) and NEFA (p < 0.05) increased when 2 % propolis was supplied, while weight and body fat were reduced (p < 0.05) and lean mass increased. Lastly, the propolis supplement improves calcium deposition in the spleen, lungs, testes, and femur (p < 0.05). (AU)
Asunto(s)
Animales , Masculino , Ratas , Própolis/farmacología , Composición Corporal/efectos de los fármacos , Glándulas Endocrinas/efectos de los fármacos , Tejido Adiposo/efectos de los fármacos , Minerales/metabolismo , Ratas Wistar , Suplementos DietéticosRESUMEN
INTRODUCTION: Introduction: propolis and its components influence lipid metabolism; however, its effect on body composition and mineral metabolism remains unknown. Objectives: to determine the effect of natural propolis supplementation on body composition, mineral metabolism, and the endocrine function of adipose tissue. Material and methods: twenty albino male Wistar rats (8 weeks old) were divided into two groups of 10 animals each. The rats were fed two different types of diet for 90 days: a standard diet for the control group (group C) and the same standard diet + 2 % propolis (group P). Thyroid hormones, ghrelin, leptin, adiponectin and insulin, non-esterified fatty acids (NEFA) in plasma, body composition (lean mass, fat mass and body water), and mineral deposition in target organs (spleen, brain, heart, lungs, testicles, kidneys and femur) were assessed. Results: thyroid stimulating hormone (TSH), triiodothyronine (T3) and thyroxine (T4) did not show any differences after supplementation with propolis, while ghrelin and adiponectin decreased (p < 0.01 and p < 0.05, respectively) and insulin (p < 0.01), leptin (p < 0.05) and NEFA (p < 0.05) increased when 2 % propolis was supplied, while weight and body fat were reduced (p < 0.05) and lean mass increased. Lastly, the propolis supplement improves calcium deposition in the spleen, lungs, testes, and femur (p < 0.05). Conclusion: propolis supplementation of the diet (2 %) causes a decrease in the secretion of ghrelin and adiponectin, increasing the release of non-esterified fatty acids and the rate of insulin secretion. In addition, propolis supplementation induces an improvement in calcium deposition in target organs without affecting the rest of minerals, which improves body composition by inducing a reduction in weight and visceral adipose tissue, and improvement in lean mass.
INTRODUCCIÓN: Introducción: el propóleo y sus componentes influyen en el metabolismo lipídico; sin embargo, se desconoce su efecto sobre la composición corporal y el metabolismo mineral. Objetivos: determinar el efecto de la suplementación de la dieta con propóleo natural sobre la composición corporal, el metabolismo basal y mineral, y la función endocrina del tejido adiposo. Material y métodos: veinte ratas albinas Wistar macho (8 semanas) se dividieron en dos grupos de 10 animales cada uno. Las ratas fueron alimentadas con dos tipos diferentes de dietas durante 90 días: una dieta estándar para el grupo de control (grupo C) y la misma dieta estándar + un 2 % de propóleo (grupo P). Se determinaron las hormonas tiroideas, la grelina, la leptina, la adiponectina y la insulina, los ácidos grasos no esterificados (AGNE) en el plasma, la composición corporal (masa magra, masa grasa y agua corporal) y el depósito de minerales en órganos diana (bazo, cerebro, corazón, pulmones, testículos, riñones y fémur). Resultados: los niveles plasmáticos de hormona estimulante del tiroides (TSH), triyodotironina (T3) y tiroxina (T4) no mostraron diferencias tras la ingesta del suplemento de propóleo, mientras que los de grelina y adiponectina disminuyeron (p < 0,01 y p < 0,05, respectivamente) y los de insulina (p < 0,01), leptina (p < 0,05) y AGNE (p < 0,05) aumentaron cuando la dieta se suplementó con propóleo al 2 %. Se redujeron el peso y la grasa corporal (p < 0,05), incrementándose la masa magra. Por último, el suplemento de propóleo mejoró el depósito de calcio en el bazo, los pulmones, los testículos y el fémur (p < 0,05). Conclusión: el suplemento de propóleo al 2 % de la dieta produjo una disminución de la secreción de grelina y adiponectina, incrementando la concentración de AGNE y aumentando la tasa de secreción de insulina. Además, el suplemento de propóleo indujo una mejora del depósito de calcio en los órganos diana sin afectar al resto de minerales, lo que en conjunto mejora la composición corporal al inducir una reducción del peso y del tejido adiposo visceral, mejorando la masa magra.
Asunto(s)
Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/fisiología , Composición Corporal/efectos de los fármacos , Suplementos Dietéticos , Glándulas Endocrinas/efectos de los fármacos , Glándulas Endocrinas/fisiología , Minerales/metabolismo , Própolis/farmacología , Animales , Masculino , Ratas , Ratas WistarRESUMEN
CONTEXT: Although stages of reproductive aging for women in the general population are well described by STRAW+10 criteria, this is largely unknown for female adolescent and young adult cancer survivors (AYA survivors). OBJECTIVE: This work aimed to evaluate applying STRAWâ +â 10 criteria in AYA survivors using bleeding patterns with and without endocrine biomarkers, and to assess how cancer treatment gonadotoxicity is related to reproductive aging stage. DESIGN: The sample (nâ =â 338) included AYA survivors from the Reproductive Window Study cohort. Menstrual bleeding data and dried-blood spots for antimüllerian hormone (AMH) and follicle-stimulating hormone (FSH) measurements (Ansh DBS enzyme-linked immunosorbent assays) were used for reproductive aging stage assessment. Cancer treatment data were abstracted from medical records. RESULTS: Among participants, mean age 34.0â ±â 4.5 years and at a mean of 6.9â ±â 4.6 years since cancer treatment, the most common cancers were lymphomas (31%), breast (23%), and thyroid (17%). Twenty-nine percent were unclassifiable by STRAWâ +â 10 criteria, occurring more frequently in the first 2 years from treatment. Most unclassifiable survivors exhibited bleeding patterns consistent with the menopausal transition, but had reproductive phase AMH and/or FSH levels. For classifiable survivors (48% peak reproductive, 30% late reproductive, 12% early transition, 3% late transition, and 7% postmenopause), endocrine biomarkers distinguished among peak, early, and late stages within the reproductive and transition phases. Gonadotoxic treatments were associated with more advanced stages. CONCLUSIONS: We demonstrate a novel association between gonadotoxic treatments and advanced stages of reproductive aging. Without endocrine biomarkers, bleeding pattern alone can misclassify AYA survivors into more or less advanced stages. Moreover, a large proportion of AYA survivors exhibited combinations of endocrine biomarkers and bleeding patterns that do not fit the STRAWâ +â 10 criteria, suggesting the need for modified staging for this population.
Asunto(s)
Envejecimiento , Antineoplásicos/efectos adversos , Supervivientes de Cáncer/estadística & datos numéricos , Glándulas Endocrinas/patología , Neoplasias/tratamiento farmacológico , Insuficiencia Ovárica Primaria/patología , Reproducción , Adolescente , Adulto , Hormona Antimülleriana/sangre , Glándulas Endocrinas/efectos de los fármacos , Femenino , Hormona Folículo Estimulante/sangre , Estudios de Seguimiento , Humanos , Menopausia , Neoplasias/patología , Insuficiencia Ovárica Primaria/inducido químicamente , Pronóstico , Estudios Prospectivos , Adulto JovenRESUMEN
The present study was designed to evaluate the effects of di-n-hexyl phthalate (DHP) and di-cyclohexyl phthalate (DCHP) on endocrine organs in rats. Oil control, 20-, 100-, and 500 mg/kg dose groups were selected and administered to pregnant rats on gestational days 6-19 by oral gavage. The neonatal stages of rats continued until postnatal day 20 and the- juvenile stages of rats continued until postnatal day of 32. The rats were allowed to mature until the neonatal and juvenile stages and there after, they were divided into four groups corresponding to the treatment levels. Body and organ weights were recorded, serum was collected, and thyroid, pancreas, pituitary gland, and adrenal gland were removed. There was a decrease in body weights in the 20- and 500mg/kg DHP and in the 20-mg/kg DCHP dose groups in neonatal male rats. In contrast, for female rats, there was an increase in body weights in the 100-mg/kg DCHP dose group and there was a decrease in body weights in the 500-mg/kg DHP dose group. Body weights were increased at 20 and 500 mg/kg in the DHP-exposed juvenile male rats. Serum thyroid-stimulating hormone (TSH) levels were increased in neonatal male rats, while they were increased in the 100-mg/kg DHP group of neonatal and juvenile female rats. Serum triiodothyronine (T3) levels were increased at the high dose of DHP for neonatal male rats and at the low and high dose levels of DCHP for female rats. Serum thyroxine (T4) levels were increased in neonatal rats for DHP. Also, some histopathological changes were observed in the thyroid, pancreas, adrenal, and pituitary gland. In conclusion, it was shown that DHP and DCHP caused negative effects on T3, T4, and TSH hormone levels.
Asunto(s)
Glándulas Endocrinas/efectos de los fármacos , Ácidos Ftálicos/farmacología , Efectos Tardíos de la Exposición Prenatal/epidemiología , Animales , Peso Corporal , Relación Dosis-Respuesta a Droga , Femenino , Masculino , Tamaño de los Órganos/efectos de los fármacos , Embarazo , Ratas , Ratas Wistar , Factores Sexuales , Hormonas Tiroideas/biosíntesis , Tirotropina/biosíntesis , Tiroxina/biosíntesisRESUMEN
Bacterial lipopolysaccharide (LPS) can contribute to the pathogenesis and the clinical symptoms of many diseases such as cancer, mental disorders, neurodegenerative as well as metabolic diseases. The asymptomatic carrier state of Salmonella spp. is a very important public health problem. A subclinical single dose of LPS obtained from S. Enteritidis (5 µg/kg, i.v.) was administered to discern the consequences of changes of various brain peptides such as corticotropin-releasing hormone (CRH), gonadotropin-releasing hormone (GnRH), thyrotropin-releasing hormone (TRH), galanin (GAL), neuropeptide Y (NPY), somatostatin (SOM), substance P (SP), and vasoactive intestinal polypeptide (VIP) in selected clinically important brain sections and endocrine glands of the hypothalamic-pituitary-adrenal (HPA), -thyroid (HPT), -ovarian (HPO) axes. The study was conducted on ten immature crossbred female pigs. The brain peptides were extracted from the hypothalamus (medial basal hypothalamus, preoptic area, lateral hypothalamic area, mammillary bodies, and the stalk median eminence), and pituitary gland (adenohypophysis and neurohypophysis) sections and from the ovaries and adrenal and thyroid glands. There was no difference in health status between LPS and the control groups during the period of the experiment. Nevertheless, even a low single dose of LPS from S. Enteritidis that did not result in any clinical symptoms of disease induced dysregulation of various brain peptides, such as CRH, GnRH, TRH, GAL, NPY, SOM, SP, and VIP in selected brain sections of hypothalamus, pituitary gland and in the endocrine glands of the HPA, HPO, and HPT axes. In conclusion, the obtained results clearly show that subclinical LPS from S. Enteritidis can affect the brain chemistry structure and dysregulate bioactive substance from selected brain sections and glands of the neuroendocrine axes. The exact mechanisms by which LPS can influence major neuroendocrine axes are not fully understood and require further studies.
Asunto(s)
Encéfalo/efectos de los fármacos , Glándulas Endocrinas/efectos de los fármacos , Lipopolisacáridos/farmacología , Ovario/efectos de los fármacos , Hormonas Peptídicas/metabolismo , Salmonella enteritidis , Animales , Encéfalo/metabolismo , Glándulas Endocrinas/metabolismo , Femenino , Ovario/metabolismo , PorcinosRESUMEN
The number of patients surviving ≥5 years after initial cancer diagnosis has significantly increased during the last decades due to considerable improvements in the treatment of many cancer entities. A negative consequence of this is that the emergence of long-term sequelae and endocrine disorders account for a high proportion of these. These late effects can occur decades after cancer treatment and affect up to 50% of childhood cancer survivors. Multiple predisposing factors for endocrine late effects have been identified, including radiation, sex, and age at the time of diagnosis. A systematic literature search has been conducted using the PubMed database to offer a detailed overview of the spectrum of late endocrine disorders following oncological treatment. Most data are based on late effects of treatment in former childhood cancer patients for whom specific guidelines and recommendations already exist, whereas current knowledge concerning late effects in adult-onset cancer survivors is much less clear. Endocrine sequelae of cancer therapy include functional alterations in hypothalamic-pituitary, thyroid, parathyroid, adrenal, and gonadal regulation as well as bone and metabolic complications. Surgery, radiotherapy, chemotherapy, and immunotherapy all contribute to these sequelae. Following irradiation, endocrine organs such as the thyroid are also at risk for subsequent malignancies. Although diagnosis and management of functional and neoplastic long-term consequences of cancer therapy are comparable to other causes of endocrine disorders, cancer survivors need individually structured follow-up care in specialized surveillance centers to improve care for this rapidly growing group of patients.
Asunto(s)
Antineoplásicos/efectos adversos , Enfermedades del Sistema Endocrino/inducido químicamente , Inmunoterapia/efectos adversos , Neoplasias/tratamiento farmacológico , Radioterapia/efectos adversos , Procedimientos Quirúrgicos Operativos/efectos adversos , Antineoplásicos/uso terapéutico , Glándulas Endocrinas/efectos de los fármacos , Glándulas Endocrinas/efectos de la radiación , Enfermedades del Sistema Endocrino/epidemiología , Enfermedades del Sistema Endocrino/etiología , Enfermedades del Sistema Endocrino/fisiopatología , Femenino , Humanos , Masculino , Neoplasias/radioterapia , Neoplasias/cirugía , Neoplasias/terapiaRESUMEN
Oligomers of styrene have been identified in polystyrene (PS) polymer samples intended for food packaging. Such oligomers contribute to nonintentionally added substances (NIAS) that may migrate into food or food simulants and therefore have to be assessed for the potential risk to health. No oligomers larger than dimers and trimers of styrene have been found to be present in PS. Some in vivo and in vitro information indicative of an endocrine activity for some specific oligomers suggest concerns for their potential for endocrine disruption in humans. Data on endocrine activity available from in vitro and in vivo screening approaches and from non-guideline studies in experimental animals were evaluated. The different test methods were classified according to the OECD Conceptual Framework for Testing and Assessment of Endocrine Disruptors (OECD) and the ranking system of Borgert et al. proposed in 2014. The quality and reliability of each study is further assessed by professional judgment. The integration of the total information supports the conclusion that neither specific oligomers, nor their mixtures, potentially migrating into food are endocrine disruptors according to the definition of EFSA and WHO/IPCS.
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Disruptores Endocrinos/toxicidad , Poliestirenos/toxicidad , Animales , Disruptores Endocrinos/farmacología , Glándulas Endocrinas/efectos de los fármacos , Femenino , Embalaje de Alimentos , Humanos , Masculino , Poliestirenos/química , Poliestirenos/farmacología , Reproducibilidad de los ResultadosRESUMEN
Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. However, because ICIs block coinhibitory molecules on T cells and other immune cells, unleashing them to mediate tumor cell killing, they also can disrupt the maintenance of immunological tolerance to self-antigens. Compared with chemotherapy, ICIs have a different toxicity profile, especially the occurrence of autoimmune-like manifestations against multiple organ systems, including endocrine glands, commonly referred to as immune-related adverse events. The aim of this review was to provide practical recommendations regarding the proper assessment and clinical management related to the new onset of endocrinopathies after the use of ICIs in patients with cancer. Cancer 2018;124:1111-21. © 2018 American Cancer Society.
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Antineoplásicos Inmunológicos/efectos adversos , Receptores Coestimuladores e Inhibidores de Linfocitos T/antagonistas & inhibidores , Enfermedades del Sistema Endocrino/diagnóstico , Neoplasias/tratamiento farmacológico , Antineoplásicos Inmunológicos/administración & dosificación , Autoinmunidad/efectos de los fármacos , Receptores Coestimuladores e Inhibidores de Linfocitos T/inmunología , Glándulas Endocrinas/efectos de los fármacos , Glándulas Endocrinas/inmunología , Enfermedades del Sistema Endocrino/inducido químicamente , Enfermedades del Sistema Endocrino/terapia , Humanos , Neoplasias/inmunología , Guías de Práctica Clínica como AsuntoRESUMEN
Amphibians inhabiting montane riparian zones in the Neotropics are particularly vulnerable to decline, but the reasons are poorly understood. Because environmental contaminants, endocrine disruption, and pathogens often figure prominently in amphibian declines it is imperative that we understand how these factors are potentially interrelated to affect montane populations. One possibility is that increased precipitation associated with global warming promotes the deposition of contaminants in montane regions. Increased exposure to contaminants, in turn, potentially elicits chronic elevations in circulating stress hormones that could contribute to montane population declines by compromising resistance to pathogens and/or production of sex steroids regulating reproduction. Here, we test this hypothesis by examining contaminant levels, stress and sex steroid levels, and nematode abundances in male drab treefrogs, Smilisca sordida, from lowland and montane populations in Costa Rica. We found no evidence that montane populations were more likely to possess contaminants (i.e., organochlorine, organophosphate and carbamate pesticides or benzidine and chlorophenoxy herbicides) than lowland populations. We also found no evidence of elevational differences in circulating levels of the stress hormone corticosterone, estradiol or progesterone. However, montane populations possessed lower androgen levels, hosted more nematode species, and had higher nematode abundances than lowland populations. Although these results suggested that nematodes contributed to lower androgens in montane populations, we were unable to detect a significant inverse relationship between nematode abundance and androgen level. Our results suggest that montane populations of this species are not at greater risk of exposure to contaminants or chronic stress, but implicate nematodes and compromised sex steroid levels as potential threats to montane populations.
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Anuros/parasitología , Disruptores Endocrinos/toxicidad , Contaminantes Ambientales/toxicidad , Animales , Anuros/sangre , Anuros/fisiología , Corticosterona/sangre , Costa Rica , Disruptores Endocrinos/metabolismo , Glándulas Endocrinas/efectos de los fármacos , Glándulas Endocrinas/fisiopatología , Contaminantes Ambientales/metabolismo , Calentamiento Global , Hormonas Esteroides Gonadales/sangre , Interacciones Huésped-Parásitos , Masculino , Nematodos/aislamiento & purificación , Nematodos/patogenicidad , Dinámica Poblacional , Estrés Fisiológico , Clima Tropical/efectos adversosRESUMEN
Phytochemicals are non-nutrient bioactive compounds occurring in plants and food, which possess the capacity to modulate one or more metabolic processes or pathways in the body, resulting to health benefits and promotion of well-being. The interest of the scientific community continues to grow, powered by progressive research efforts to identify properties and potential applications of bioactive substances, and coupled with public interest and consumer demand. However, the natural derivation of these compounds is not a feature of harmlessness, over that of therapeutic efficacy, to which is also added the absence of post-marketing monitoring which does not allow to evaluate the occurrence of adverse effects related to the use of their related products. The literature is particularly rich of studies concerning phytochemicals as environmental estrogens, which result in infertility, reproductive abnormalities, and tumors but also in some endocrine-related health effects. Nevertheless, further studies have been performed to better understand the bioavailability, pharmacokinetics and mode of action of these compounds which seems to go beyond their ability to bind to oestrogen receptors and either stimulate or inhibit the activity of endogenous oestrogens, highlighting new interesting target molecules and signaling pathways. The present review summarizes the latest developments and knowledge concerning the assessment of endocrine activities of dietary phytochemicals focusing on pharmacological aspects.
Asunto(s)
Glándulas Endocrinas/efectos de los fármacos , Fitoquímicos/farmacología , Animales , Disponibilidad Biológica , Dieta , Humanos , Simulación del Acoplamiento Molecular , Fitoquímicos/química , Fitoquímicos/farmacocinéticaRESUMEN
BACKGROUND: Phthalates, such as dibutyl phthalate (DBP), are endocrine disruptors used in some medication coatings e.g., mesalamine to treat inflammatory bowel disease (IBD). OBJECTIVES: Taking advantage of different mesalamine formulations with/without DBP, we assessed whether DBP from mesalamine (>1000x background) altered serum hormones. METHODS: Men (N=73) with IBD participated in a crossover-crossback prospective study and provided up to 6 serum samples (2:baseline, 2:crossover, 2:crossback). Men on non-DBP mesalamine (background) at baseline crossed-over for 4 months to DBP-mesalamine (high) and then crossed-back for 4 months to non-DBP mesalamine (B1HB2-arm) and vice versa for men on DBP-mesalamine at baseline (H1BH2-arm). We divided H1BH2-arm at the median (H1<3yrs or H1≥3yrs). We estimated crossover and crossback % changes in serum reproductive hormones using multivariable linear mixed effect models. RESULTS: When B1HB2-arm (26 men,134 samples) crossed-over, luteinizing hormone decreased 13.9% (95% confidence interval(CI): -23.6,-3.0) and testosterone, inhibin-B, and follicle-stimulating hormone (FSH) marginally decreased; after crossback all increased 8-14%. H1BH2-arm, H1≥3yrs (25 men,107samples) had no changes at crossover or crossback whereas in H1BH2-arm,H1<3yrs (22 men,100 samples) after crossover, inhibin-B increased 13.2% (CI: 4.2,22.9), FSH decreased 9.9% (CI: -17.9,-1.1) and after crossback, inhibin-B further increased 11.3%, and FSH marginally increased. CONCLUSIONS: High-DBP exposure may disrupt pituitary-gonadal hormones that largely reversed after exposure removal, but only in men with no or short previous high-exposure history. Paradoxically, men with longer duration of high-DBP exposure, exposure removal did not change hormone levels, suggesting that long-term high-DBP exposure may alter the pituitary-gonadal axis and make it insensitive to exposure changes.
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Dibutil Ftalato/efectos adversos , Glándulas Endocrinas/efectos de los fármacos , Hormonas Gonadales/sangre , Gonadotropinas Hipofisarias/sangre , Plastificantes/efectos adversos , Adulto , Antiinflamatorios no Esteroideos/administración & dosificación , Estudios Cruzados , Humanos , Masculino , Mesalamina/administración & dosificación , Estudios ProspectivosRESUMEN
IMPORTANCE: If not promptly recognized, endocrine dysfunction can be life threatening. The incidence and risk of developing such adverse events (AEs) following the use of immune checkpoint inhibitor (ICI) regimens are unknown. OBJECTIVE: To compare the incidence and risk of endocrine AEs following treatment with US Food and Drug Administration-approved ICI regimens. DATA SOURCES: A PubMed search through July 18, 2016, using the following keywords was performed: "ipilimumab," "MDX-010," "nivolumab," "BMS-963558," "pembrolizumab," "MK-3475," "atezolizumab," "MPDL3280A," and "phase." STUDY SELECTION: Thirty-eight randomized clinical trials evaluating the usage of these ICIs for treatment of advanced solid tumors were identified, resulting in a total of 7551 patients who were eligible for a meta-analysis. Regimens were categorized by class into monotherapy with a PD-1 (programmed cell death protein 1) inhibitor, a CTLA-4 (cytotoxic T-lymphocyte-associated protein-4) inhibitor, or a PD-L1 (programmed cell death 1 ligand 1) inhibitor, and combination therapy with PD-1 plus CTLA-4 inhibitors. DATA EXTRACTION AND SYNTHESIS: The data were extracted by 1 primary reviewer (R.B.-S.) and then independently reviewed by 2 secondary reviewers (W.T.B. and A.C.G.-C.) following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Inferences on the incidence of AEs were made using log-odds random effects models. MAIN OUTCOMES AND MEASURES: Incidence of all-grade hypothyroidism, hyperthyroidism, hypophysitis, primary adrenal insufficiency, and insulin-deficient diabetes. RESULTS: Overall, 38 randomized clinical trials comprising 7551 patients were included in this systematic review and meta-analysis. The incidence of both hypothyroidism and hyperthyroidism was highest in patients receiving combination therapy. Patients on the combination regimen were significantly more likely to experience hypothyroidism (odds ratio [OR], 3.81; 95% CI, 2.10-6.91, P < .001) and hyperthyroidism (OR, 4.27; 95% CI, 2.05-8.90; P = .001) than patients on ipilimumab. Compared with patients on ipilimumab, those on PD-1 inhibitors had a higher risk of developing hypothyroidism (OR, 1.89; 95% CI, 1.17-3.05; P = .03). The risk of hyperthyroidism, but not hypothyroidism, was significantly greater with PD-1 than with PD-L1 inhibitors (OR, 5.36; 95% CI, 2.04-14.08; P = .002). While patients who received PD-1 inhibitors were significantly less likely to experience hypophysitis than those receiving ipilimumab (OR, 0.29; 95% CI, 0.18-0.49; P < .001), those who received combination therapy were significantly more likely to develop it (OR, 2.2; 95% CI, 1.39-3.60; P = .001). For primary adrenal insufficiency and insulin-deficient diabetes no statistical inferences were made due to the smaller number of events. CONCLUSIONS AND RELEVANCE: Our study provides more precise data on the incidence of endocrine dysfunctions among patients receiving ICI regimens. Patients on combination therapy are at increased risk of thyroid dysfunction and hypophysitis.
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Anticuerpos Monoclonales/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Puntos de Control del Ciclo Celular , Enfermedades del Sistema Endocrino/inducido químicamente , Enfermedades del Sistema Endocrino/epidemiología , Inhibidores de Proteínas Quinasas/efectos adversos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Puntos de Control del Ciclo Celular/inmunología , Glándulas Endocrinas/efectos de los fármacos , Glándulas Endocrinas/fisiopatología , Humanos , Inmunoterapia/efectos adversos , Incidencia , Neoplasias/tratamiento farmacológico , Neoplasias/epidemiología , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricosRESUMEN
OBJECTIVE: To determine whether adding dehydroepiandrosterone to combined oral contraceptives (COCs) maintains physiological levels of free testosterone. STUDY DESIGN: A randomized, double-blind, placebo-controlled, two-way crossover study conducted in 81 healthy women (age range: 20-35 years; Body mass index (BMI) range: 18-35 kg/m2) using oral contraceptives. Androgens, sex hormone-binding globulin (SHBG), estradiol (E2) and estrone (E1) were measured, and free testosterone and the free testosterone index were calculated. Subjects discontinued oral contraceptive use for at least one menstrual cycle before being randomized to receive five cycles of ethinyl estradiol (EE) combined with either levonorgestrel (EE/LNG group) or drospirenone (EE/DRSP group) together with either dehydroepiandrosterone (DHEA) (50 mg/day orally) or placebo. Subsequently, all subjects crossed over to the other treatment arm for an additional five cycles. RESULTS: Both COCs decreased the levels of all androgens measured. Significant decreases (p<.05) were found with EE/LNG and EE/DRSP for total testosterone (54.5% and 11.3%, respectively) and for free testosterone (66.8% and 75.6%, respectively). Adding DHEA to the COCs significantly increased all androgens compared to placebo. Moreover, including DHEA restored free testosterone levels to baseline values in both COC groups and total testosterone levels to baseline in the EE/LNG group and above baseline in the EE/DRSP group. SHBG concentrations were significantly higher with EE/DRSP compared to EE/LNG (p<.0001). The addition of DHEA did not affect the levels of SHBG. CONCLUSIONS: Taking COCs reduces total and free testosterone levels and increases SHBG concentrations. By coadministration with DHEA, physiological levels of total and free testosterone are restored while using EE/LNG. With EE/DRSP, only the free testosterone level is normalized by DHEA coadministration. IMPLICATIONS: A daily oral dose of 50-mg DHEA maintains physiological free and total testosterone levels in women who are using an EE/LNG-containing COC.
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Anticonceptivos Orales Combinados/efectos adversos , Anticonceptivos Hormonales Orales/efectos adversos , Deshidroepiandrosterona/efectos adversos , Testosterona/sangre , Adulto , Androstenos/efectos adversos , Estudios Cruzados , Método Doble Ciego , Regulación hacia Abajo/efectos de los fármacos , Combinación de Medicamentos , Glándulas Endocrinas/efectos de los fármacos , Glándulas Endocrinas/metabolismo , Estradiol/sangre , Estradiol/química , Estradiol/metabolismo , Estrona/antagonistas & inhibidores , Estrona/sangre , Estrona/metabolismo , Etinilestradiol/efectos adversos , Femenino , Humanos , Levonorgestrel/efectos adversos , Países Bajos , Reproducibilidad de los Resultados , Globulina de Unión a Hormona Sexual/agonistas , Globulina de Unión a Hormona Sexual/análisis , Globulina de Unión a Hormona Sexual/metabolismo , Solubilidad , Testosterona/agonistas , Testosterona/antagonistas & inhibidores , Testosterona/metabolismo , Adulto JovenRESUMEN
CONTEXT: Arecoline is an effective constituent of Areca catechu L. (Arecaceae) with various pharmacological effects. However, investigations also revealed that long use of arecoline could arouse some oral diseases. OBJECTIVE: The present review gathers the fragmented information available in the literature (before 1 October 2015) regarding pharmacology and toxicology of arecoline. We also discussed the potential developments and applications of arecoline in the future. METHODS: All the available information regarding the arecoline is compiled from scientific databases, including Science Direct, PubMed, Web of Science, Scopus, etc. RESULTS: Previous research demonstrated that arecoline is one of the major effective constituents in A. catechu. Additionally, arecoline has a wide spectrum of pharmacological activities including effects on nervous, cardiovascular, digestive and endocrine systems and anti-parasitic effects. What's more, arecoline is reported to be the primary toxic constituent of A. catechu, and the main toxic effects include oral submucous fibrosis (OSF), oral squamous cell carcinoma (OSCC) and genotoxicity. CONCLUSION: Arecoline has great potential to be a therapeutic drug for various ailments. However, further investigations are needed in the future to reduce or eliminate its toxicities before developing into new drug.
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Arecolina/farmacología , Animales , Arecolina/uso terapéutico , Arecolina/toxicidad , Sistema Cardiovascular/efectos de los fármacos , Glándulas Endocrinas/efectos de los fármacos , Humanos , Sistema Nervioso/efectos de los fármacosRESUMEN
The present study was designed to test the effects of methylphenidate (MPH) exposure on the maturation of endocrine functioning and sexual behavior. Female rat pups received either MPH (2.0mg/kg, i.p.) or saline twice daily between postnatal days 20-35. This period of exposure represents the time just prior to puberty as well as puberty onset. Approximately five weeks after the last injection of MPH or saline, female subjects were hormone-primed and tested during their first sexual experience. Subjects were given the choice to interact with a sexually active male or a sexually receptive female rat (i.e., the partner-preference test). The partner-preference paradigm allows us to assess multiple aspects of female sexual behavior. MPH exposure during peri-adolescence delayed puberty and, when mated for the first time, affected sexual behavior (e.g., increased time spent with the male stimulus and decreased the likelihood of leaving after mounts) during the test of partner preference. When monitoring estrous cyclicity, female subjects treated with MPH during peri-adolescence frequently experienced irregular estrous cycles. The results of the present study suggest that chronic exposure to a therapeutic dose of MPH around the onset of puberty alters long-term endocrine functioning, but with hormone priming, increases sensitivity to sexual stimuli.
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Glándulas Endocrinas/efectos de los fármacos , Metilfenidato/administración & dosificación , Conducta Sexual Animal/efectos de los fármacos , Maduración Sexual , Animales , Glándulas Endocrinas/fisiología , Estro/efectos de los fármacos , Femenino , Ratas , Ratas Long-EvansRESUMEN
The European Commission lists styrene (S) as an endocrine disruptor based primarily on reports of increased prolactin (PRL) levels in S-exposed workers. The US Environmental Protection Agency included S in its list of chemicals to be tested for endocrine activity. Therefore, the database of S for potential endocrine activity is assessed. In vitro and in vivo screening studies, as well as non-guideline and guideline investigations in experimental animals indicate that S is not associated with (anti)estrogenic, (anti)androgenic, or thyroid-modulating activity or with an endocrine activity that may be relevant for the environment. Studies in exposed workers have suggested elevated PRL levels that have been further examined in a series of human and animal investigations. While there is only one definitively known physiological function of PRL, namely stimulation of milk production, many normal stress situations may lead to elevations without any chemical exposure. Animal studies on various aspects of dopamine (DA), the PRL-regulating neurotransmitter, in the central nervous system did not give mechanistic explanations on how S may affect PRL levels. Overall, a neuroendocrine disruption of PRL regulation cannot be deduced from a large experimental database. The effects in workers could not consistently be reproduced in experimental animals and the findings in humans represented acute reversible effects clearly below clinical and pathological levels. Therefore, unspecific acute workplace-related stress is proposed as an alternative mode of action for elevated PRL levels in workers.