RESUMO
AIMS: To evaluate the concentration of hyaluronan acid and proliferation/cellular death in mammary gland of ovariectomized female rat after estroprogestative therapy. MATERIALS AND METHODS: Forty ovariectomized female rats were divided into four groups with 10 animals/each: OG (vehicle); EG: (Estradiol, 7 days of treatment), PG (Progesterone acetate, 23 days of treatment), and EPG: (Estradiol, 7 days of treatment, and next Progesterone acetate, 23 days of treatment). Twenty-four hours after the last treatment, all animals were euthanized, the mammary gland removed, then, a fragment was immersed in acetone to quantifying of the hyaluronan acid biochemical method (ELISA-Like fluorometric assay), and a fragment fixed for 24 h in 10% formaldehyde in phosphate-buffered saline (PBS) processed for immunohistochemistry method for detection of the cell marker proliferation (Ki67) and cellular marker death by DNA fragmentation the TUNEL method. RESULTS: The estradiol-treatment alone (EG) or associated with progesterone (EPG) affected the concentration of hyaluronan acid, increased cell proliferation, and decreased cell death compared to OG and PG (p < .05) in the mammary tissue. CONCLUSIONS: Our results suggest that the excessive reduction of HA in mammary tissue, as occurred with progesterone treatment, can lead to a breakdown of the extracellular matrix. These changes may be indicative of mammary pathology such as the development of tumor.
Assuntos
Estradiol , Ácido Hialurônico , Glândulas Mamárias Animais , Progesterona , Animais , Morte Celular , Proliferação de Células , Estradiol/farmacologia , Feminino , Ácido Hialurônico/análise , Glândulas Mamárias Animais/efeitos dos fármacos , Glândulas Mamárias Animais/patologia , Progesterona/farmacologia , RatosRESUMO
In this study, we report the synthesis and structural characterization of a series of thiosemicarbazone and 4-thiazolidinones derivatives, as well as their in vitro antiproliferative activity against eight human tumor cell lines. For the most potent compound further studies were performed evaluating cell death induction, cell cycle profile, ctDNA interaction and topoisomerase IIα inhibition. A synthetic three-step route was established for compounds (2a-e and 3a-d) with yields ranging from 32 to 95%. Regarding antiproliferative activity, compounds 2a-e and 3a-d showed mean GI50 values ranging between 1.1 µM (2b) - 84.65 µM (3d). Compound 2b was the most promising especially against colorectal adenocarcinoma (HT-29) and leukemia (K562) cells (GI50 = 0.01 µM for both cell lines). Mechanism studies demonstrated that 24 h-treatment with compound 2b (5 µM) induced phosphatidylserine residues exposition and G2/M arrest on HT-29 cells. Moreover, 2b (50 µM) was able to interact with ctDNA and inhibited topoisomerase IIα activity. These results demonstrate the importance of thiosemicarbazone, especially the derivative 2b, as a promising candidate for anticancer therapy.
Assuntos
Antineoplásicos/farmacologia , Proteínas de Ligação a DNA/antagonistas & inibidores , Indóis/farmacologia , Tiazolidinas/farmacologia , Tiossemicarbazonas/farmacologia , Inibidores da Topoisomerase/farmacologia , Antígenos de Neoplasias/metabolismo , Antineoplásicos/síntese química , Antineoplásicos/química , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , DNA Topoisomerases Tipo II/metabolismo , Proteínas de Ligação a DNA/metabolismo , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Indóis/síntese química , Indóis/química , Estrutura Molecular , Relação Estrutura-Atividade , Tiazolidinas/síntese química , Tiazolidinas/química , Tiossemicarbazonas/síntese química , Tiossemicarbazonas/química , Inibidores da Topoisomerase/síntese química , Inibidores da Topoisomerase/químicaRESUMO
The aim of the present study was to evaluate the capacity of some root canal irrigants to induce genetic damage and/or cellular death in vitro. Murine fibroblast cells were exposed to ethylenediaminetetraacetic acid (EDTA), sodium hypochlorite (NaOCl), MTAD and citric acid in increasing concentrations for 3 h at 37ºC. The negative control group was treated with vehicle control (phosphate buffer solution - PBS) for 3 h at 37°C, and the positive control group was treated with methylmetanesulfonate, 1 μM. for 3 h at 37°C. Cytotoxicity was assessed by the trypan blue test and genotoxicity was evaluated by the single cell gel (comet) assay. The results showed that exposure to 2.5% and 5% NaOCl and 8.5% citric acid resulted in a significant cytotoxic effect. NaOCl, EDTA and citric acid did not produce genotoxic effects with respect to the comet assay data for all evaluated concentrations. Although MTAD was not a cytotoxic agent, it showed significant genotoxic effects at all tested concentrations (ANOVA and Tukey's test; p<0.05). NaOCl, EDTA and citric acid were found to be cytotoxic in a dose-dependent manner, but they were not genotoxic. MTAD did not cause cell death, but presented genotoxic effects.
O objetivo do presente estudo foi avaliar a capacidade de alguns irrigantes endodônticos em induzir danos genéticos e/ou morte celular in vitro. Células de fibroblastos murinos foram expostas ao ácido etilenodiaminotetracético (EDTA), hipoclorito de sódio (NaOCl), MTAD e ácido cítrico em concentrações crescentes durante 3 h a 37°C. O grupo controle negativo foi tratado com solução tampão fosfato - PBS por 3 h a 37° C e o grupo controle positivo foi tratado com metilmetanesulfonato a 1 μM por 3 h a 37° C. A citotoxicidade foi testada pelo azul de tripan e a genotoxicidade foi avaliada pelo teste do cometa. Os resultados apontaram que a exposição ao NaOCl a 2,5% e 5%, e ácido cítrico a 21% resultou em efeitos citotóxicos significativos. O NaOCl, EDTA e o ácido cítrico não produziram efeitos genotóxicos no que diz respeito aos dados obtidos pelo ensaio do Cometa em todas as concentrações testadas. Embora o MTAD não tenha sido um agente citotóxico, mostrou efeitos genotóxicos significativos em todas as concentrações testadas (ANOVA e teste de Tuckey; p<0,05). O NaOCl, o EDTA e o ácido cítrico mostraram-se citotóxicos de maneira dose-dependente, mas não genotóxicos. Por outro lado, apesar do MTAD não ter causado a morte celular, foi genotóxico em todas as concentrações testadas.
Assuntos
Animais , Camundongos , Morte Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Dentina/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Mutagênicos , Irrigantes do Canal Radicular/toxicidade , Análise de Variância , Linhagem Celular , Ensaio Cometa , Ácido Cítrico/toxicidade , Doxiciclina/toxicidade , Ácido Edético/toxicidade , Fibroblastos/citologia , Polissorbatos/toxicidade , Hipoclorito de Sódio/toxicidade , Azul Tripano/químicaRESUMO
OBJECTIVES: The purpose of this study was to evaluate the capacity of BioPure MTAD to induce genetic damage in vitro. Genotoxicity was assessed by the single cell gel (comet) assay. METHODS: Chinese hamster ovary (CHO) cells or murine fibroblasts cells were exposed to increasing final concentrations ranging from 0.1 a 10%. All treatments were performed for 1 hour at 37 degrees C. The negative control group was treated with vehicle control (phosphate buffer solution - PBS) for 1 hour at 37 degrees C and the positive control group was treated with methylmetanesulfonate (at 1 muM) for 1 hour at 37 degrees C. RESULTS: Present results showed that the BioPure MTAD was able to promote DNA breakage in CHO cells only at the highest concentration tested as well as to induce significant increase in tail moment at all tested concentrations in murine fibroblasts. CONCLUSIONS: In summary, our results indicate that BioPure MTAD is a genotoxic agent as depicted by the single cell gel (comet) assay. (Eur J Dent 2009;3:285-289).
RESUMO
O desenvolvimento tardio da doença de Alzheimer (AD) pode ser um reflexo dos fatores ambientais que operam sobre o curso da vida. As realizações educacionais e ocupacionais foram identificadas como fatores de proteção ao desenvolvimento da doença, contudo, a colaboração de atividades físicas e passivas tem recebido pouca atenção. Além disso, muitos estudos mostraram que a limitação dietética (ingestão reduzida de calorias) pode aumentar a resistência dos neurônios ao surgimento de disfunções e morte celular em modelos experimentais da doença de Alzheimer, doença de Parkinson e doença de Huntington. © Ciências & Cognição 2005; Vol. 06: 145-147.(AU)
The development of Alzheimer's disease (AD) later in life may be reflective of environmental factors operating over the course of a lifetime. Educational and occupational attainments have been found to be protective against the development of the disease, but participation in these activities has received little attention. Besides many studies have shown that dietary restriction (reduced calorie intake) can increase the resistance of neurons in the brain to dysfunction and death in experimental models of disease, Parkinson's disease, and Huntington's disease. © Ciências & Cognição 2005; Vol. 06: 145-147.(AU)