RESUMO
Agathisflavone (AGF) is a biflavonoid with a number of important biological and pharmacological activities, such as antioxidant, antimicrobial, and neuroprotective effects. However, its toxicological effects have not been fully investigated. Accordingly, the aim of this study was to investigate the toxicological effects of AGF in mice. For this purpose, the median lethal dose 50% (LD50) was determined along with the anatomic and histopathological parameters (weight, alimentation, excretion, biochemical, and hematological) in fertile untouched female Swiss mice. Results suggest that during the treatment, no deaths were reported at 300 and 2000 mg/kg (n = 03/group, p.o.). Moreover, AGF did not cause significant change in the above mentioned parameters in test animals when compared with the control group (0.05% Tween 80 dissolved in 0.9% saline). Taken all together, this non-clinical toxicological study revealed that AGF has an LD50 larger than 2000 mg/kg and did not change significantly the hematological, biochemical, histopathological, behavioral, as well as physiological parameters in the female mice.
Assuntos
Biflavonoides/toxicidade , Extratos Vegetais/toxicidade , Animais , Biflavonoides/isolamento & purificação , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Dose Letal Mediana , Camundongos , Extratos Vegetais/isolamento & purificação , Folhas de Planta , Desempenho Psicomotor/efeitos dos fármacos , Desempenho Psicomotor/fisiologia , Teste de Desempenho do Rota-Rod/métodosRESUMO
This study evaluates a correlation between family history, micronutrients intake, and alternative therapies with genetic instability, before and during breast cancer treatment. For this study, a total of 150 women were selected. Among those, 50 women were breast cancer patients on chemotherapy, while 50 breast cancer patients were on radiotherapy, and 50 were healthy females. All the participants signed the informed consent form and answered the public health questionnaire. Samples of buccal epithelial and peripheral blood cells were collected and analyzed through micronucleus and comet assays. The cells were evaluated for apoptosis and DNA damage. Results showed the association of patients' family history with an increase in toxicogenetic damage before and during cancer therapy. On the other hand, patients with late-onset cancer also presented genetic instability before and during therapy, along with those who did not take sufficient vegetables and alternative therapies. A positive correlation was observed between the genetic instability and alternative therapies, while inverse correlation was recorded with the vegetable consumption. Results clearly explain that the nutritional aspects and alternative therapies influence the genetic instability before and during cancer therapies especially in radiotherapy treated patients. Our data could be used for the monitoring therapies and management of breast cancer patients.
Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/fisiopatologia , Terapias Complementares , Dieta , Instabilidade Genômica , Anamnese , Estudos de Casos e Controles , Ensaio Cometa , Feminino , Frutas , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , VerdurasRESUMO
This study aimed to evaluate DNA damage in patients with breast cancer before treatment (background) and after chemotherapy (QT) and radiotherapy (RT) treatment using the Comet assay in peripheral blood and the micronucleus test in buccal cells. We also evaluated repair of DNA damage after the end of RT, as well as the response of patient's cells before treatment with an oxidizing agent (H2O2; challenge assay). Fifty women with a mammographic diagnosis negative for cancer (control group) and 100 women with a diagnosis of breast cancer (followed up during the treatment) were involved in this study. The significant DNA damage was observed by increasing in the index and frequency of damage along with the increasing of the frequency of micronuclei in peripheral blood and cells of the buccal mucosa, respectively. Despite the variability of the responses of breast cancer patients, the individuals presented lesions on the DNA, detected by the Comet assay and micronucleus Test, from the diagnosis until the end of the oncological treatment and were more susceptible to oxidative stress. We can conclude that the damages were due to clastogenic and/or aneugenic effects related to the neoplasia itself and that they increased, especially after RT.
Assuntos
Neoplasias da Mama/genética , Dano ao DNA/genética , Adulto , Células Cultivadas , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Feminino , Humanos , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Testes para Micronúcleos , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacosRESUMO
Molecular epidemiological studies have identified several risk factors linking to the genes and external factors in the pathogenesis of breast cancer. In this sense, genetic instability caused by DNA damage and DNA repair inefficiencies are important molecular events for the diagnosis and prognosis of therapies. Therefore, the objective of this study was to analyze correlation between sociocultural, occupational, and lifestyle risk factors with levels of genetic instability in non-neoplastic cells of breast cancer patients. Total 150 individuals were included in the study that included 50 breast cancer patients submitted to chemotherapy (QT), 50 breast cancer patients submitted to radiotherapy (RT), and 50 healthy women without any cancer. Cytogenetic biomarkers for apoptosis and DNA damage were evaluated in samples of buccal epithelial and peripheral blood cells through micronuclei and comet assay tests. Elder age patients (61-80 years) had higher levels of apoptosis (catriolysis by karyolysis) and DNA damage at the diagnosis (baseline damage) with increased cell damage during QT and especially during RT. We also reported the increased frequencies of cytogenetic biomarkers in patients who were exposed to ionizing radiation as well as for alcoholism and smoking. QT and RT induced high levels of fragmentation (karyorrhexis) and nuclear dissolution (karyolysis) and DNA damage. Correlations were observed between age and karyorrhexis at diagnosis; smoking and karyolysis during RT; and radiation and karyolysis during QT. These correlations indicate that risk factors may also influence the genetic instability in non-neoplastic cells caused to the patients during cancer therapies.