RESUMO
Synthetic estrogens such as ethinylestradiol (EE2) are persistent micropollutants that are not effectively removed from wastewater by conventional treatments. These contaminants are released into waterbodies, where they disrupt endocrine systems of organisms and cause harmful effects such as feminization, infertility, reproduction problems and genital malformations. The consequences of this pollution for key marine ecosystems such as coral reefs and their associated microbiomes are underexplored. We evaluated the effects of EE2 concentrations of 100 ng L-1 and 100 µg L-1 on the coral metaorganism Mussismilia harttii. The results indicated no effects on visible bleaching or Fv/Fm ratios in the corals during a 17-day microcosm experiment. However, next-generation sequencing of 16S rDNA revealed a statistically significant effect of high EE2 concentrations on OTU richness, and shifts in specific microbial groups after treatments with or without EE2. These groups might be bioindicators of early shifts in the metaorganism composition caused by EE2 contamination.
Assuntos
Antozoários/efeitos dos fármacos , Recifes de Corais , Congêneres do Estradiol/toxicidade , Etinilestradiol/toxicidade , Poluentes Químicos da Água/toxicidade , AnimaisRESUMO
17α-ethinylestradiol (EE2) is a synthetic estrogen that can cause harmful effects on animals, such as male feminization and infertility. However, the impact of the EE2 contamination on microbial communities and the potential role of bacterial strains as bioremediation agents are underexplored. The aim of this work was to evaluate the impact of EE2 on the microbial community dynamics of aerated submerged fixed-film reactors (ASFFR) simulating a polishing step downstream of a secondary sewage treatment. For this purpose, the reactors were fed with a synthetic medium with low COD content (around 50 mg l-1), supplemented (reactor H) or not (reactor C) with 1 µg l-1 of EE2. Sludge samples were periodically collected during the bioreactors operation to assess the bacterial profile over time by 16S rRNA gene amplicon sequencing or by bacterial isolation using culture-dependent approach. The results revealed that the most abundant phyla in both reactors were Proteobacteria and Bacteroidetes. At genus level, Chitinophagaceae, Nitrosomonas and Bdellovibrio predominated. Significant effects caused by EE2 treatment and bioreactors operating time were observed by non-metric multidimensional scaling. Therefore, even at low concentrations as 1 µg l-1, EE2 is capable of influencing the bioreactor microbiome. Culture-dependent methods showed that six bacterial isolates, closely related to Pseudomonas and Acinetobacter genera, could grow on EE2 as the sole carbon source under aerobic conditions. These organisms may potentially be used for the assembly of an EE2-degrading bacterial consortium and further exploited for bioremediation applications, including tertiary sewage treatment to remove hormone-related compounds not metabolized in secondary depuration stages.
Assuntos
Congêneres do Estradiol , Microbiota , Animais , Reatores Biológicos , Estrogênios , Etinilestradiol , Masculino , RNA Ribossômico 16S , EsgotosRESUMO
This work reports for the first time the use of laminar cork as a sorptive phase in a microextraction technique, rotating-disk sorptive extraction (RDSE). Typical hormones (estrone, estradiol, estriol and ethinyl estradiol) were selected as analyte models and extracted from wastewater samples on laminar cork with statistically equivalent extraction efficiency to that provided by Oasis HLB. The cork characterization was performed by confocal fluorescence microscopy (CLSM), Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM), allowing the identification of lignin, suberin and polysaccharides (cellulose and hemicellulose) as the main components of the cork. The best conditions for extraction were as follows: rotation velocity of the disk, 2000â¯rpm; extraction time, 45â¯min; and sample volume, 20â¯mL. The analytical features of the developed method show that calibration curves for all analytes have R2 values higher than 0.99. The absolute recoveries were higher than 63%, and the precision, expressed as relative standard deviation, ranged from 2 to 16%. The LOD and LOQ ranges were 3-19 and 10-62â¯ngâ¯L-1, respectively. The proposed method was applied to the analysis of wastewater, and the concentrations of hormones in a wastewater treatment plant in Santiago, Chile, ranged from Assuntos
Congêneres do Estradiol/isolamento & purificação
, Quercus/química
, Águas Residuárias/química
, Poluentes Químicos da Água/isolamento & purificação
, Madeira/química
, Adsorção
, Congêneres do Estradiol/análise
, Cromatografia Gasosa-Espectrometria de Massas
, Química Verde/instrumentação
, Química Verde/métodos
, Limite de Detecção
, Reprodutibilidade dos Testes
, Extração em Fase Sólida/instrumentação
, Extração em Fase Sólida/métodos
, Águas Residuárias/análise
, Poluentes Químicos da Água/análise
RESUMO
Hormone active agents constitute a dangerous class of pollutants. Among them, those agents that mimic the action of estrogens on target cells and are part of the group of endocrine-disruptor compounds (EDCs) are termed estrogenic EDCs, the main focus of this review. Exposure to these compounds causes a number of negative effects, including breast cancer, infertility and animal hermaphroditism. However, especially in underdeveloped countries, limited efforts have been made to warn people about this serious issue, explain the methods of minimizing exposure, and develop feasible and efficient mitigation strategies at different levels and in various environments. For instance, the use of bioremediation processes capable of transforming EDCs into environmentally friendly compounds has been little explored. A wide diversity of estrogen-degrading microorganisms could be used to develop such technologies, which include bioremediation processes for EDCs that could be implemented in biological filters for the post-treatment of wastewater effluent. This review describes problems associated with EDCs, primarily estrogenic EDCs, including exposure as well as the present status of understanding and the effects of natural and synthetic hormones and estrogenic EDCs on living organisms. We also describe potential biotechnological strategies for EDC biodegradation, and suggest novel treatment approaches for minimizing the persistence of EDCs in the environment.
Assuntos
Disruptores Endócrinos/análise , Poluentes Químicos da Água/análise , Poluição da Água/estatística & dados numéricos , Animais , Biodegradação Ambiental , Conservação dos Recursos Naturais , Monitoramento Ambiental , Política Ambiental , Congêneres do Estradiol , Estrogênios , Estrona/análise , Humanos , Águas Residuárias , Microbiologia da ÁguaRESUMO
The presence of micropollutants in sewage is already widely known, as well as the effects caused by natural and synthetic hormones. Thus, it is necessary to apply treatments to remove them from water systems, such as advanced oxidation processes (AOPs) and membrane separation processes, which can oxidize and remove high concentrations of organic compounds. This work investigated the removal of 17ß-estradiol (E2), 17α-ethinylestradiol (EE2), and estriol (E3) from biotreated sewage. Reverse osmosis processes were conducted at three recoveries (50, 60, and 70 %). For E2 and EE2, the removals were affected by the recovery. The best results for RO were as follows: the E2 compound removal was 89 % for 60 % recovery and the EE2 compound removal was 57 % for 50 % recovery. The RO recovery did not impact the E3 removal. It was concluded that the interaction between the evaluated estrogens, and the membrane was the major factor for the hormone separation. The AOP treatment using H2O2/UV was carried out in two sampling campaigns. First, we evaluated the variation of UV doses (24.48, 73.44, 122.4, and 244.8 kJ m-2) with 18.8 mg L-1 of H2O2 in the reaction. EE2 showed considerable removals (around 70 %). In order to optimize the results, an experimental design was applied. The best result was obtained with higher UV dose (122.4 kJ m-2) and lower H2O2 concentration (4 mg L-1), achieving removal of 91 % for E3 and 100 % for E2 and EE2.
Assuntos
Congêneres do Estradiol/química , Congêneres do Estradiol/isolamento & purificação , Membranas Artificiais , Esgotos/química , Poluentes Químicos da Água/química , Poluentes Químicos da Água/isolamento & purificação , Purificação da Água/métodos , Peróxido de Hidrogênio/química , Oxirredução , Raios UltravioletaRESUMO
The synthetic estrogen 17α-ethinylestradiol, the principal component of oral contraceptives, has been identified as one of the main compounds accounting for adverse effects on the endocrine system in various species. This study aimed to analyze the state-of-the-art in legislation and guidelines for the control of this synthetic estrogen in water bodies in Europe and the United States and to draw a parallel with the Brazilian reality. Countries have generally attempted to expand the regulation and monitoring of certain emerging micropollutants not previously covered by legislation. Europe is more advanced in terms of water quality, while in the United States this estrogen is only regulated in water for human consumption. Brazil still lacks legal provisions or standards for this estrogen, which can be explained by the relatively limited maturity of the country's system for controlling water pollutants.
Assuntos
Congêneres do Estradiol/efeitos adversos , Congêneres do Estradiol/análise , Etinilestradiol/efeitos adversos , Etinilestradiol/análise , Poluentes Químicos da Água/efeitos adversos , Poluentes Químicos da Água/análise , Poluição da Água/legislação & jurisprudência , Brasil , Disruptores Endócrinos/efeitos adversos , Disruptores Endócrinos/análise , Estrogênios , Europa (Continente) , Água Doce/análise , Água Doce/química , Humanos , Estados UnidosRESUMO
The aim of this study was to explore the expression of PI3K, AKT, and P-AKT, and to investigate the role of PI3K/AKT signaling pathway in thin endometrium. We included 40 women treated in affiliated Shenzhen Nanshan People's Hospital of Guangdong Medical University for endometrial conditions between August 2013 and January 2015, 20 with a normal endometrium, and 20 with thin endometrium. The expression of PI3K, AKT, and P-AKT was evaluated by the immunohistochemical S-P method. The expression of PI3K, AKT, and P-AKT proteins was significantly lower in the thin endometrium group than in the normal endometrium group (P < 0.05). The expression of PI3K and AKT was positively correlated with the expression of P-AKT. The expression of PI3K, AKT, and P-AKT proteins in the thin endometrium decreases during the proliferative phase, and this process could be associated with PI3K/AKT signaling.
Assuntos
Endométrio/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfoproteínas/genética , Proteínas Proto-Oncogênicas c-akt/genética , Adulto , Estudos de Casos e Controles , Endométrio/patologia , Congêneres do Estradiol/sangue , Feminino , Regulação da Expressão Gênica , Humanos , Fosfatidilinositol 3-Quinases/sangue , Fosfoproteínas/sangue , Congêneres da Progesterona/sangue , Proteínas Proto-Oncogênicas c-akt/sangue , Transdução de SinaisRESUMO
O estrogênio sintético 17α-etinilestradiol, principal componente utilizado em formulações de contraceptivos orais, tem sido apontado como um dos principais compostos responsáveis por provocar efeitos adversos no sistema endócrino de várias espécies. O objetivo deste estudo foi analisar o estado da arte dos dispositivos legais e normativos referentes ao controle desse estrogênio sintético nas águas da Europa e dos Estados Unidos, e traçar um paralelo com a realidade brasileira. No geral, os países têm buscado ampliar a regulamentação e monitoramento de alguns micropoluentes emergentes que antes não eram objeto de atenção por parte dos dispositivos legais. A Europa está mais avançada no que tange à qualidade dos corpos hídricos, enquanto que nos Estados Unidos esta substância é alvo de regulamentação apenas para a água destinada ao consumo humano. No Brasil, ainda não há nenhum dispositivo legal ou normativo que aborde esse estrogênio, o que pode ser associado a uma baixa maturidade do sistema brasileiro quanto ao controle de poluentes hídricos.
El estrógeno sintético 17α-etinilestradiol, principal componente utilizado en fórmulas de contraceptivos orales, ha sido apuntado como uno de los principales compuestos responsables por provocar efectos adversos en el sistema endócrino de varias especies. El objetivo de este estudio fue analizar el estado de la cuestión de los dispositivos legales y normativos referentes al control de este estrógeno sintético en las aguas de Europa y de los Estados Unidos, y trazar un paralelo con la realidad brasileña. En general, los países han buscado ampliar la regulación y el monitoreo de algunos microcontaminantes emergentes que antes no eran objeto de atención por parte de los dispositivos legales. Europa está más avanzada en lo que se refiere a la calidad de los cuerpos hídricos, mientras que en los Estados Unidos esta substancia es objeto de regulación solamente para el agua destinada al consumo humano. En Brasil todavía no existe ningún dispositivo legal o normativo que aborde este estrógeno, lo que puede ser asociado a una inmadurez del sistema brasileño respecto al control de contaminantes hídricos.
The synthetic estrogen 17α-ethinylestradiol, the principal component of oral contraceptives, has been identified as one of the main compounds accounting for adverse effects on the endocrine system in various species. This study aimed to analyze the state-of-the-art in legislation and guidelines for the control of this synthetic estrogen in water bodies in Europe and the United States and to draw a parallel with the Brazilian reality. Countries have generally attempted to expand the regulation and monitoring of certain emerging micropollutants not previously covered by legislation. Europe is more advanced in terms of water quality, while in the United States this estrogen is only regulated in water for human consumption. Brazil still lacks legal provisions or standards for this estrogen, which can be explained by the relatively limited maturity of the country's system for controlling water pollutants.
Assuntos
Humanos , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/efeitos adversos , Poluição da Água/legislação & jurisprudência , Congêneres do Estradiol/análise , Congêneres do Estradiol/efeitos adversos , Etinilestradiol/análise , Etinilestradiol/efeitos adversos , Estados Unidos , Brasil , Estrogênios , Disruptores Endócrinos/análise , Disruptores Endócrinos/efeitos adversos , Europa (Continente) , Água Doce/análise , Água Doce/químicaRESUMO
Contraceptive drugs are nowadays found in aquatic environments around the globe. Particularly, 17α-ethinylestradiol (EE2) may act even at low concentrations, such as those recorded in natural ecosystems. We evaluated the physiological effects of EE2 on cyclopoids and calanoids, common copepods in both marine and freshwater communities. We used three EE2 concentrations and assessed its impact on activity of different physiological endpoints: Acetylcholinesterase (neurotransmission), Glutathione S-transferase (detoxifying system), and Caspase-3 (apoptosis). While EE2 exerts, distinctive effect on detoxifying and apoptotic systems, no effect on AChE was observed at environmental doses. Our results show that EE2 exposure affects differently copepod physiology endpoints, altering moulting process, adult recruitment in calanoids and calanoid to cyclopoid ratio. The ecological consequences of this underlying physiological process may affect since life history to population and community structures, and this represent a new aspects of this xenobiotic in natural systems.
Assuntos
Congêneres do Estradiol/toxicidade , Invertebrados/crescimento & desenvolvimento , Poluentes Químicos da Água/toxicidade , Animais , Caspase 3/metabolismo , Demografia , Disruptores Endócrinos/análise , Disruptores Endócrinos/toxicidade , Congêneres do Estradiol/análise , Etinilestradiol/análise , Etinilestradiol/toxicidade , Glutationa Transferase/metabolismo , Invertebrados/classificação , Invertebrados/efeitos dos fármacos , Estágios do Ciclo de Vida , Poluentes Químicos da Água/análiseRESUMO
OBJECTIVES: This work evaluated chronic treatment with 17ß-oestradiol (E2) and 17ß-aminoestrogen pentolame (AEP) on prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), and fibrinogen concentration (FIB). Male (M) and ovariectomized (Ovx) Wistar rats were used to explore gender differences in the pharmacological response. MATERIALS AND METHODS: Rats (n=12-18) were treated every third day during three months with E2 (1, 10, 100 µg/kg), AEP (1, 10, 100, 500 µg/kg) or vehicle (propylenglycol 1 ml/ kg). PT, aPTT, TT, and FIB were measured using standardized techniques. RESULTS: Chronic treatment with E2 in male rats increased PT (4-7%; P<0.05), decreased aPTT (9%; 100 µg/kg; P<0.05) and decreased TT (5% at 100 µg/Kg; P<0.05). Chronic treatment with E2 in ovariectomized female rats decreased PT (3-4%; P<0.05), did not induce significant changes on aPTT and decreased TT in a dose dependent manner (12-27%; P<0.05). Chronic treatment with AEP in male rats did not alter PT, increased aPTT in a dose dependent manner (5-16%; P<0.05), and decreased TT (5%; 500 µg/Kg; P<0.05) while in female ovariectomized rats it decreased PT (5-9%; P<0.05), increased aPTT (8-13%; P<0.05) and decreased TT (6-13%; P<0.05). E2 and AEP decreased FIB in M and Ovx animals. Decreases in FIB by E2 were more pronounced in male (15-18% P<0.05) than in ovariectomized rats (10-14% P<0.05). E2 showed more potency than AEP, lowering FIB at 1 and 10 µg/kg doses. Both estrogens decreased FIB in ovariectomized animals (E2, 10-14%, P<0.05; AEP, 9% P<0.05) and were reverted by increasing dosage. CONCLUSIONS: Gender influenced response to chronic treatment with E2 and AEP on hemostatic parameters. PT and aPTT were the most affected parameters, demonstrating non-equivalence in the pharmacological response of M and Ovx rats.
Assuntos
Amino Álcoois/farmacologia , Congêneres do Estradiol/farmacologia , Estradiol/farmacologia , Estrenos/farmacologia , Estrogênios/farmacologia , Hemostasia/efeitos dos fármacos , Animais , Testes de Coagulação Sanguínea , Feminino , Masculino , Ovariectomia , Ratos , Ratos Wistar , Caracteres SexuaisRESUMO
BACKGROUND: Buame [17ß-(butylamino)-1,3,5(10)-estratrien-3-ol] possesses anticoagulant and antiplatelet activities that are potentially antithrombotic. Since its estrogenicity is unknown, it was evaluated by established methods. METHODS: Buame (10, 100, 500, and 1,000 µg/kg), 17ß-estradiol (E(2)) (100 µg/kg), or propylene glycol (10 ml/kg) were subcutaneously (sc) administered for three days to immature Wistar female rats (21 days old). The relative uterotrophic effect to E(2) was 78 (E(2) = 100) with a relative uterotrophic potency of 1.48 (E(2) = 100). Adult ovariectomized Wistar rats received an sc injection at 8:00 h (reversed cycle) of: 7.5 µg of E(2) (≈ 30 µg/kg), buame (≈ 750, 1,500, 3,000 µg/kg), or corn oil (≈ 1.2 ml/kg). After 24 h, progesterone (4-5 mg/kg) was administered. Sexual receptivity was assessed 5 to 7 h later, and the lordosis quotient (LQ; number lordosis/number mounts x 100) was evaluated. RESULTS: Buame induced lordosis (LQmax 85 ± 9; ED50 952 ± 19 µg/kg) and E(2) LQmax 56 ± 8; ED50 10 ± 2 µg/kg; the relative LQ-potency was 0.51 (E(2) = 100). Buame competed with [(3)H]E(2) for the estrogen receptor (Buame RBA= 0.15 and Ki = 5.9 x 10(-7) M; E(2) RBA= 100;Ki = 6.6 x 10(-9) M). Buame increased MCF-7 cells proliferation, from 10(-11) to 10(-)9 M, its proliferative effect was 1.73-1.79 (E(2) = 3.0-3.9); its relative proliferative effect to E(2) was 33-40% (E(2) = 100%) and relative potency 10.4-10.7 (E(2) = 100). Tamoxifen and fulvestrant (ICI 182,780) inhibited buame's proliferation indicating mediation through estrogen receptors in this response. CONCLUSION: Buame is therefore an estrogen partial agonist with a weak estrogenic activity.
Assuntos
Estradiol/farmacologia , Estrogênios/farmacologia , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Óleo de Milho/farmacologia , Estradiol/análogos & derivados , Congêneres do Estradiol/farmacologia , Feminino , Fulvestranto , Humanos , Lordose/tratamento farmacológico , Lordose/metabolismo , Células MCF-7 , Progesterona/administração & dosagem , Propilenoglicol/farmacologia , Ratos , Ratos Wistar , Receptores de Estrogênio/metabolismo , Comportamento Sexual Animal/efeitos dos fármacos , Tamoxifeno/farmacologiaRESUMO
Compounds with estrogenic effects that also inhibit platelet aggregation might be useful in reducing thrombotic events associated with estrogenic therapy. In this study, two aminoestrogens, Buame [N-(3-hydroxy-1,3,5(10)-estratrien-17ß-yl)-butylamine] and Diebud [N,N'-bis-(3-hydroxy-1,3,5(10)-estratrien-17ß-yl)-1,4-butanediamine], were synthesized and characterized using common analytical methods and spectrophotometric analyses. The location and orientation of these molecules on the estrogenic receptor α (ERα) were also evaluated. Platelet inhibitory effects were elucidated ADP-induced platelet aggregation and ADP- and collagen-induced ATP release. Molecular docking demonstrated that Buame can reach and bind to the ERα in the ligand binding domain (LBD) similar to 17ß-estradiol (co-crystallized ligand). On the other hand, Diebud binds only to the surface of ERα due to its high molecular volume compared to 17ß-estradiol and Buame.
Assuntos
Congêneres do Estradiol/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Difosfato de Adenosina/farmacologia , Trifosfato de Adenosina/metabolismo , Adulto , Sítios de Ligação , Colágeno/farmacologia , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Congêneres do Estradiol/química , Congêneres do Estradiol/metabolismo , Receptor alfa de Estrogênio/química , Receptor alfa de Estrogênio/metabolismo , Humanos , Lipossomos/química , Masculino , Pessoa de Meia-Idade , Modelos Moleculares , Estrutura Molecular , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/metabolismo , Ligação Proteica , Estrutura Terciária de Proteína , Adulto JovemRESUMO
17beta-aminoestrogens (AEs) produce anticoagulant effects in rats contrastingwith 17beta-estradiol (E2) procoagulant effects, their estrogenic effects are similar to E2, decreasing serum luteinizing hormone (LH), increasing uterine weight (Uw), activate transcription through the ERalpha and ERbeta receptors and pentolame induces progesterone (P) receptors in the anterior pituitary of ovariectomized (Ovx) rats similarly to E2, suggesting possible effects on female rats' sexual behavior. This work evaluated the AEs prolame, butolame, pentolame compared to E2 and estradiol benzoate (EB) as facilitators on the rat lordotic behavior. Dose-response curves were performed in rats by single subcutaneous (s.c.) injection (timezero) of: E2 (approximately 0.3, 3, 30, 60, 300 microg/kg); EB (approximately 0.4, 4, 40, 80, 400 microg/kg); prolame, butolame, pentolame (approximately 40, 400, 2000 or 4000 mg/kg), vehicle (corn oil; 300 microL/day; approximately 1.2 mL/kg) as control; 24 h after, P (1 mg/rat in 100 microL of corn oil; approximately 4 to 5 mg/kg) was administered, and 5 to 7 h later LQ was evaluated (number of lordosis displays/number of mounts x 100). E2, EB and AEs followed by P administration, induced lordosis in a dose-dependent manner. Prolame induced an LQEmax of 92, butolame85, EB 81, pentolame 44 and E2 43. The most potent was EB (LQED50 of 4.1 +/- 0.5 microg/kg); then E2 10 microg +/- 2.2/kg; prolame 268 +/- 19 microg/kg; butolame 402 +/- 21 microg/kg, and pentolame 1037 +/- 28 microg/kg. The AEs LQ potency decreases as length substitution on the amine group in C-17 increases. AEs LQDE50 values correlate with previous Uw DE50, LH ID50 and binding studies indicates mediation of the response by estrogen receptors. AEs facilitate sexual behavior of Ovx rats as partial estrogenic agonists.
Assuntos
Congêneres do Estradiol/farmacologia , Estradiol/fisiologia , Estrenos/farmacologia , Comportamento Sexual Animal/efeitos dos fármacos , Amino Álcoois/farmacologia , Análise de Variância , Animais , Relação Dose-Resposta a Droga , Feminino , Masculino , Postura , Progesterona/fisiologia , Ratos , Ratos Wistar , Comportamento Sexual Animal/fisiologia , Estatísticas não ParamétricasRESUMO
A significant increase for cardiovascular disease and breast cancer risks was found in the Women's Health Initiative study in 2002, for current users of conjugated equine estrogens in the habitual dose of 0.625 mg for hormone replacement therapy (HRT) for treating menopausal symptoms. This unexpected finding has caused new-found interest in the world to determine if the use of low-dose estrogens or synthetic estrogens can be useful and safer. At present, there is no scientific evidence about the reduction of such risks with the use of low-dose estrogens. Current medical information has showed that HRT is effective to treat climacteric syndrome and to prevent postmenopausal osteoporosis. In addition, HRT reduces significantly the frequency and severity of vaginal bleeding. Currently the Climacteric and Menopause Program at the Instituto Mexicano del Seguro Social only considers the use of conjugated equine estrogens at the standard dose (0.625 mg). The purpose of this paper is to present some results about use of low-dose estrogens and points of view about synthetic estrogens found in current medical literature. This review aims at contributing to the analysis a possible future use of this type of hormone treatment within the institutional program with the goal of giving safer options to clinicians in managing women with menopausal symptoms.
Assuntos
Congêneres do Estradiol/administração & dosagem , Terapia de Reposição de Estrogênios , Estrogênios/administração & dosagem , Menopausa , Estrogênios/efeitos adversos , Feminino , Humanos , Menopausa/efeitos dos fármacosAssuntos
Disruptores Endócrinos/efeitos adversos , Exposição Ambiental , Estrogênios/efeitos adversos , Praguicidas/efeitos adversos , Anormalidades Induzidas por Medicamentos/etiologia , Adulto , Animais , Neoplasias da Mama/induzido quimicamente , DDT/efeitos adversos , DDT/farmacologia , Disruptores Endócrinos/farmacologia , Poluentes Ambientais/efeitos adversos , Poluentes Ambientais/farmacologia , Congêneres do Estradiol/efeitos adversos , Congêneres do Estradiol/farmacologia , Estrogênios/farmacologia , Estrogênios não Esteroides/efeitos adversos , Estrogênios não Esteroides/farmacologia , Feminino , Humanos , Recém-Nascido , Infertilidade Masculina/induzido quimicamente , Masculino , Praguicidas/farmacologia , Fitoestrógenos/efeitos adversos , Fitoestrógenos/análise , Fitoestrógenos/farmacologia , Gravidez , Espanha , Toxicologia/organização & administração , Universidades/organização & administraçãoRESUMO
A novel microemulsion based on sodium bis(2-ethylhexyl) sulfosuccinate (AOT) was developed for the simultaneous determination of natural and synthetic estrogens by microemulsion EKC (MEEKC). The microemulsion system consisted of 1.4% w/w AOT, 1.0% w/w octane, 7.0% w/w 1-butanol and 90.6% w/w 20 mM sodium salt of 3-(cyclohexylamino)-2-hydroxy-1-propanesulfonic acid (CAPSO) and 10 mM phosphate buffer at pH 12.5. A baseline resolution in the separation of estrone, 17beta-estradiol, estriol, estradiol 17-hemisuccinate, etinilestradiol, estradiol 3-benzoate, and estradiol 17-valerate was achieved in comparison to the traditional MEEKC system with SDS in less than 15 min. The optimized electrophoretic conditions included the use of an uncoated-silica capillary of 60 cm of total length and 75 microm id, an applied voltage of 25 kV, a temperature of 25 degrees C and 214 UV-detection. Parameters of validation such as specificity, linearity, accuracy, LOD, LOQ and robustness were evaluated according to international guidelines. Due to its simplicity, accuracy, and reliability, the proposed method can be an advantageous alternative to the traditional methodologies for the analysis of natural and synthetic estrogens in different pharmaceutical forms.
Assuntos
Cromatografia Capilar Eletrocinética Micelar/métodos , Emulsões/química , Congêneres do Estradiol/isolamento & purificação , Soluções Tampão , Cromatografia Capilar Eletrocinética Micelar/instrumentação , Congêneres do Estradiol/química , Concentração de Íons de Hidrogênio , Preparações Farmacêuticas/análise , Sensibilidade e Especificidade , Solubilidade , Succinatos/química , Tensoativos/químicaRESUMO
Estrogens have been associated with thromboembolic events. Our group has described the anticoagulant effect of 17 beta-aminoestrogens in rodents, potentially new alternative estrogenic agents without thrombogenic risk. This work compares the contrasting effects of estradiol and the 17 beta-aminoestrogens (prolame, butolame, and pentolame) on blood clotting time. Ovariectomized CD1 mice received a single injection of 17beta-aminoestrogens, estradiol (20 to 80 mg/kg), or vehicle. Estradiol decreased blood clotting time from -10% to -25% (48 h; P<0.01) and 17 beta-aminoestrogens increased it, differing in latency (approximately 12 h; +48%, P<0.01) and duration (approximately 72 h +58%, P<0.01). In male Wistar rats, similar effects (pentolame +45%; estradiol -31%; P<0.01) were observed 48 h after five consecutive daily injections of 1000 microg/animal/day. The maximum procoagulant effect of estradiol was obtained after 72 h with 10 microg/animal/day (-45%; P<0.01). 17 Beta-aminoestrogens always produced opposite effects to those of estradiol on blood coagulation.
Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Congêneres do Estradiol/farmacologia , Estradiol/farmacologia , Amino Álcoois/farmacologia , Animais , Relação Dose-Resposta a Droga , Estradiol/administração & dosagem , Congêneres do Estradiol/administração & dosagem , Estrenos/administração & dosagem , Estrenos/farmacologia , Feminino , Masculino , Camundongos , Ovariectomia , Ratos , Ratos WistarRESUMO
Administration of exogenous estrogens has been associated with an increase of thromboembolic events. The 17 beta-aminoestrogens produce anticoagulant effects contrasting with the procoagulant effects of the natural occurring estradiol in rodents. This work compares the estrogenic effects induced by 17 beta-aminoestrogens prolame, butolame, pentolame, and estradiol in vivo models. Dose-response curves were performed using immature CD1 mice and Wistar rats. The animals were injected with estradiol or 17 beta-aminoestrogens (0.01 to 1000 microg/kg), or vehicle. The uterine wet and dry weights were determined. The 17 beta-aminoestrogens increased uterine weight in a dose-dependent manner. The uterotrophic effect produced by estradiol induced lower ED50 (6.5 and 4 microg/kg) and higher E(max) values (+523-350%) in mice as compared with those from the rat, indicating more susceptibility of the mice model. The 17 beta-aminoestrogens are partial estrogenic agonists with a relative uterotrophic effect of estradiol (100%) from 9-86%. Only the ED50 values of 17 beta-aminoestrogens in CD1 mice showed a direct correlation to the length of the amine group substitution in C-17 since their efficacy and potency were in the order: prolame>butolame>pentolame.
Assuntos
Congêneres do Estradiol/farmacologia , Útero/efeitos dos fármacos , Amino Álcoois/administração & dosagem , Amino Álcoois/farmacologia , Animais , Relação Dose-Resposta a Droga , Estradiol/administração & dosagem , Estradiol/farmacologia , Congêneres do Estradiol/administração & dosagem , Estrenos/administração & dosagem , Estrenos/farmacologia , Feminino , Camundongos , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Wistar , Útero/anatomia & histologiaRESUMO
OBJECTIVE: To evaluate the epithelial thickness, number of vessels, amount of collagen and muscular fibers of the bladder and urethra of castrated adult female rats during the time between castration and the beginning of the administration of synthetic conjugated estrogen. METHOD: 118 adult female rats were divided into four groups: Group I (n = 30): noncastrated female rats; group II (n = 30): female rats treated with synthetic conjugated estrogen in the dose of 50 microg/animal/day for 28 days, beginning immediately after castration; group III (n = 28): female rats treated with synthetic conjugated estrogen, 50 microg/animal/day for 28 days, beginning 30 days after castration: group IV (n = 30): female rats sacrificed after 30 days of castration. The histology of the bladder wall and the medium-third of the urethra wall were evaluated after flushing with hematoxylin-eosin and picrosirius for morphometric analysis. RESULTS: It was verified that the epithelial thickness in groups II and III were similar whereas in groups I, II and III the thickness of the bladder and also the urethra were larger than in group IV. Concerning the bladder groups I and II were similar. In group I the urethra was superior than in groups II and III. In relation to the number of vessels and muscular fibers, groups I, II and III were similar to each other and superior to group IV in the bladder and urethra. The amount of collagen was similar in groups I, II and III and inferior in group IV in the bladder and in the urethra. CONCLUSION: Independent of the time of estrogen administration (immediate or within 30 days) after castration, the thickness of the epithelium, the number of vessels, amount of collagen and muscular fibers were similar. The female rats with estrogen replacement presented significantly larger thickness of the epithelium, number of vessels and muscular fibers, and a smaller amount of collagen in the bladder and urethra in relation to the castrated group. Finally, estrogen therapy (immediate and 30 days after castration) reverted the effects of the estrogen deficiency in the vessels, collagen and muscular fibers, the bladder and of the urethra when compared to the group of castrated female rats, thus becoming similar to noncastrated animals.
Assuntos
Terapia de Reposição de Estrogênios , Ovariectomia , Uretra/anatomia & histologia , Bexiga Urinária/anatomia & histologia , Animais , Colágeno/análise , Epitélio/anatomia & histologia , Congêneres do Estradiol/administração & dosagem , Estrogênios Conjugados (USP)/administração & dosagem , Feminino , Músculo Liso/química , Ratos , Fatores de TempoRESUMO
Estrogênios são substâncias com ações tanto genitais quanto extragenitais, sendo utilizadas na clínica no controle de várias situações. Portanto, é importante o conhecimento do metabolismo, vias de administração, biodisponibilidade e atuação dessas substâncias sobre os diversos setores do organismo. Os autores revisam as ações dos estrogênios nos sitemas nervoso central, cardiovascular, digestivo, endócrino, urinário, locomotor e imunológico