Effect of estradiol and bisphenol A on human hepatoblastoma cell viability and telomerase activity

Sex hormones from environmental and physiological sources might play a major role in the pathogenesis of hepatoblastoma in children. This study investigated the effects of estradiol and bisphenol A on the proliferation and telomerase activity of human hepatoblastoma HepG2 cells. The cells were divided into 6 treatment groups: control, bisphenol A, estradiol, anti-estrogen ICI 182,780 (hereinafter ICI), bisphenol A+ICI, and estradiol+ICI. Cell proliferation was measured based on average absorbance using the Cell Counting-8 assay. The cell cycle distribution and apoptotic index were determined by flow cytometry. Telomerase activity was detected by polymerase chain reaction and a telomeric repeat amplification protocol assay. A higher cell density was observed in bisphenol A (P<0.01) and estradiol (P<0.05) groups compared with the control group. Cell numbers in S and G2/M phases after treatment for 48 h were higher (P<0.05), while the apoptotic index was lower (P<0.05) and telomerase activities at 48 and 72 h (P<0.05) were higher in these groups than in the control group. The cell density was also higher in bisphenol A+ICI (P<0.01) and estradiol+ICI (P<0.05) groups compared with the ICI group. Furthermore, cell numbers were increased in S and G2/M phases (P<0.05), while the apoptotic index was lower (P<0.05) and telomerase activities at 48 and 72 h were higher (P<0.05) in these groups than in the ICI group. Therefore, bisphenol A and estradiol promote HepG2 cell proliferation in vitro by inhibition of apoptosis and stimulation of telomerase activity via an estrogen receptor-dependent pathway.

Extrato de soja no tratamento dos sintomas vasomotores no período menopausal / Soybean extract in the treatment of vasomotor symptoms in menopausal period

Os sintomas vasomotores, tais como fogachos e sudorese noturna, são comuns no período menopausal. A terapia hormonal permanece como a mais efetiva no alívio desses sintomas. No entanto, desperta preocupações sob o risco de aumentar a ocorrência de doenças diretamente relacionadas ao trato genital e mamas, sendo ainda contraindicada em algumas doenças crônicas. Assim, alguns tratamentos alternativos, baseados em alimentos ou suplementos enriquecidos com fitoestrogênios, produtos químicos presentes em algumas plantas, têm sido utilizados. No entanto, existem divergências quanto a sua eficácia. Assim, realizamos esta revisão a partir de artigos recuperados da base de dados Medical Literature Analysis and Retrieval System on Line (MEDLINE), com o objetivo de tentar esclarecer se o uso das isoflavonas está relacionado à redução dos sintomas vasomotores na menopausa. A partir dos artigos recuperados, pudemos observar que não existem evidências de que o uso de fitoestrogênios por mulheres na pós-menopausa reduzem os sintomas vasomotores. Por outro lado, nenhum dos trabalhos analisados mencionou efeitos prejudiciais no uso dessas substâncias. Entretanto, estudos experimentais em animais evidenciaram, quando administradas em altas doses, a ocorrência de metaplasia endometrial.

Hot flushes and night sweats are common vasomotor symptoms during menopausal period. Hormone therapy is believable to be the most effective treatment for relieving these symptoms. However, such treatment concerns us because its use may be directly related to genital tract and breast diseases. It is also contraindicated in some chronic diseases. Thus, some alternative treatments have been used such as consuming foods or supplements enriched with phytoestrogens, which are chemical compounds present in some plants. Whereas there are disagreements regarding its effectiveness, we conducted this review based on articles retrieved from the Medical Literature Analysis and Retrieval System on Line (MEDLINE) data base. Our aim was to try clarifying whether the use of isoflavones are related to reduction of vasomotor symptoms at menopause. From the articles retrieved, we observed that there is no conclusive evidence that the use of isoflavones by postmenopausal women reduces vasomotor symptoms. On the other hand, none of the consulted articles reported harmful effects on the use of such substances. However, experimental studies in animals have shown endometrial metaplasia when they are administered in high doses.

Effects of endocrine disrupting chemicals on expression of phospholipid hydroperoxide glutathione peroxidase mRNA in rat testes

Phospholipid hydroperoxide glutathione peroxidase(PHGPx), an antioxidative selenoprotein, is modulated byestrogen in the testis and oviduct. To examine whetherpotential endocrine disrupting chemicals (EDCs) affectthe microenvironment of the testes, the expression patternsof PHGPx mRNA and histological changes were analyzedin 5-week-old Sprague-Dawley male rats exposed to severalEDCs such as an androgenic compound [testosterone (50,200, and 1,000microg/kg)], anti-androgenic compounds [flutamide(1, 5, and 25mg/kg), ketoconazole (0.2 and 1mg/kg), anddiethylhexyl phthalate (10, 50, and 250mg/kg)], andestrogenic compounds [nonylphenol (10, 50, 100, and 250mg/kg), octylphenol (10, 50, and 250mg/kg), and diethyl-stilbestrol (10, 20, and 40microg/kg)] daily for 3 weeks via oraladministration. Mild proliferation of germ cells andhyperplasia of interstitial cells were observed in the testesof the flutamide-treated group and deletion of thegerminal epithelium and sloughing of germ cells wereobserved in testes of the diethylstilbestrol-treated group.Treatment with testosterone was shown to slightly decreasePHGPx mRNA levels in testes by the reverse transcription-polymerase chain reaction. However, anti-androgeniccompounds (flutamide, ketoconazole, and diethylhexylphthalate) and estrogenic compounds (nonylphenol,octylphenol, and diethylstilbestrol) significantly up-regulated PHGPx mRNA in the testes (p<0.05). Thesefindings indicate that the EDCs might have a detrimentaleffect on spermatogenesis via abnormal enhancement ofPHGPx expression in testes and that PHGPx is useful as abiomarker for toxicity screening of estrogenic or anti-androgenic EDCs in testes.

Exposure to genistein does not adversely affect the reproductive system in adult male mice adapted to a soy-based commercial diet

Genistein, a soybean-originated isoflavone, is widely consumed by humans for putative beneficial health effects but its estrogenic activity may affect adversely the development of male reproductive system. Five-week-old ICR mice were purchased and fed with a soybean-based Purina Chow diet until 6 months of age. The animals were exposed by gavage to genistein (2.5 mg/kg/day) or 17beta-estradiol (7.5 microgram/kg/day) for five weeks. Corn oil was used for the negative control. The animals were fed the caseinbased AIN-76A diet throughout the experimental periods. There were no significant differences in body and organ weights of mice among experimental groups. No significant differences in sperm counts and sperm motile characteristics were found between the control and the genistein groups. Treatment of 17beta-estradiol caused a significant decrease in epididymal sperm counts compared to the control (p<0.05). The level of phospholipid hydroxide glutathione peroxidase in the epididymis of mice exposed to genistein was significantly higher than that of the control mice (p<0.05). 17beta-estradiol treatment caused a reduction of germ cells in the testis and hyperplasia of mucosal fold region in the prostate of mice. Genistein treatment did not cause any lesion in the testis, epididymis, and prostate. These results suggest that dietary uptake of genistein at adult stage of life may not affect male reproductive system and functions.

Fitoestrógenos dietarios y sus potenciales beneficios en la salud del adulto humano / Dietary phytoestrogen and its potential benefits in adult human health

Human diet contains a series of bioactive vegetal compounds that can improve human health. Among these, there has been a special interest for phytoestrogens. This article reviews the evidence about the potential benefits of phytoestrogens for human health. Forty eight manuscripts were selected for their study design and relevance to human health. The cell growth inhibitory effects of phytoestrogens and their implication in breast cancer are reviewed. Also the effects of these compounds on serum lipid levels and the effectiveness of a phytoestrogen derivate, ipriflavone, on the prevention of osteoporosis are analyzed. Although these compounds have a great potential for improving health, there is still not enough evidence to recommend the routine use of phytoestrogens (Rev Méd Chile 2003; 131: 1321-28).

Quão estrogênicos são os fitoestrogênios? / How estrogenic are the phytoestrogens?

O Mecanismo de ação dos estrogênios, fitoestrogênios e SERMs se faz basicamente pelo acoplamento destas substâncias aos receptores estrogênicos presentes nos núcleos dos órgão-alvo. A resposta tecidual, entretanto, poderá variar dentro de um espectro entre totalmente estimuladora ou repressora, na dependência de diversos fatores presentes em cada célula, como o tipo do receptor (alfa ou beta), a prevalência de cada um nos diversos tecidos, da sua dimerização formando homodímeros ou heterodímeros, do elemento de resposta estrogênica (ERE) e promotores vizinhos (TAF1 e TAF2), do contexto celular das proteínas adaptadoras e da potência específica do ligante. À luz dos conhecimentos da biologia molecular, poderemos interpretar as ações dos estrogênios, dos fitoestrogênios e SERMs e avaliar o real efeito de cada um, bem como suas interações. Por exemplo, um determinado serm poderá evitar a perda de massa óssea numa paciente na pós-menopausa e provocar osteoporose numa paciente em idade reprodutiva

Additive Estrogenic Activities of the Binary Mixtures of Four Estrogenic Chemicals in Recombinant Yeast Expressing Human Estrogen Receptor

To evaluate the estrogenic activities of several chemicals such as 17 beta-estradiol (E2), rho-nonylphenol, bisphenol A, butylparaben, and combinations of these chemicals, we used recombinant yeasts containing the human estrogen receptor [Saccharomyces cerevisiae ER + LYS 8127]. We evaluated E2 was most active in the recombinant yeast assay, followed by rho-nonylphenol, bisphenol A, butylparaben. The combinations of some concentrations of 17-estradiol as a strong estrogen and bisphenol A or butylparaben as a weak estrogen showed additive estrogenic effects. Also, the combinations of some concentrations of nonlyphenol and butylparaben and combination of butylparaben and bisphenol A showed additive effects in the estrogenic activity. Therefore, the estrogenic activities of the combinations of two chemicals were additive, not synergistic.

Fitoestrogênios na pós-menopausa-Revisäo / Phytoestrogens in post menopause: a review

Os fitoestrogênios säo substâncias vegetais näo esteróides, com atividades estrogênicas agonistas e antagonistas. Possuem açäo estrogênica considerada fraca, se comparados aos estrogênios naturais e sintéticos e säo encontrados principalmente na soja e seus derivados. Muitos autores têm avaliado a possibilidade do uso dos fitoestrogênios como opçäo alternativa de terapia de reposiçäo hormonal (TRH), particularmente para os casos de pacientes com contra-indicaçöes para as terapias convencionais. No presente artigo säo revisados aspectos relevantes acerca das propriedades, metabolismo e aplicabilidade dos fitoestrogênios.

Accion y efectores de Pulsatilla nigricans 3X / Action and effectors of Pulsatilla nigricans 3X

24 ratas wistar castradas se dividieron en dos lotes, inyectandolos a cada una de las del ler. grupo 0.1ml., de Pulsatilla nigricans 3X en 3 ocasiones y al segundo lote de la misma cantidad en similar forma de agua bidestilada, controlandose cada 12 horas con frotis vaginalis tenidos con la tecnica de Papanicolau y clasificandolas de acuerdo con el metodo de Allen y Doisy observandose que los 12 animal es testigos y 11 de los de experimentacion no mostraron reaccion estral. Por lo tanto, se concluye que Pulsatilla nigricans 3X, no tiene accion estrogenica y que probablemente su accion estara a nivel hipofisiario o hipotalamico, de acuerdo con lo aseverado por otros investigadores

Investigacion del poder estrogenico de Pulsatilla nigricans en ratas wistar / Estrogenic power investigation of Pulsatilla nigricans in wistar rats

Se utilizaron ratas wistar para investigar el poder estrogenico de Pulsatilla nigricans en comparacion con un grupo de animales testigo y se observaron modificaciones citologicas vaginales que nos hacen afirmar que dicho medicamento acelra en un 66.66% de los casos el ciclo estral y que dicha mutacion en los animales testigo alcanza unicamente el 8.33% mientras el 50% de los animales permanecem sin cambios citologicos cuando se les aplico el agua bidestilada y solamente el 16.66% presento esta misma condicion en los ejemplares de Pulsatilla. Ademas el estadio de estro va asociado con una ovulacion normal de los animales