RESUMEN
Arsenic is considered a worldwide pollutant that can be present in drinking water. Arsenic exposure is associated with various diseases, including cancer. Antioxidants as selenite and α-tocopherol-succinate have been shown to modulate arsenic toxic effects. Since changes in STAT3 and PSMD10 gene expression have been associated with carcinogenesis, the aim of this study was to evaluate the effect of arsenic exposure and co-treatments with selenite or α-tocopherol-succinate on the expression of these genes, in the livers of chronically exposed Syrian golden hamsters. Animals were divided into six groups: (i) control, (ii) chronically treated with 100 ppm arsenic, (iii) treated with 6 ppm α-tocopherol-succinate (α-TOS), (iv) treated with 8.5 ppm selenite, (v) treated with arsenic + α-TOS, and (vi) treated with arsenic + selenite. Urine samples and livers were collected after 20 weeks of continuous exposure. The urine samples were analyzed for arsenic species by atomic absorption spectrophotometry, and real-time RT-qPCR analysis was performed for gene expression evaluation. A reduction in STAT3 expression was observed in the selenite-treated group. No differences in PSMD10 expression were found among groups. Histopathological analysis revealed hepatic lymphocytosis in selenite-treated animals. As a conclusion, long-term exposure to arsenic does not significantly alter the expression of STAT3 and PSMD10 oncogenes in the livers of hamsters; however, selenite down-regulates STAT3 expression and provokes lymphocytosis.
Asunto(s)
Antioxidantes/farmacología , Arsénico/efectos adversos , Hígado/efectos de los fármacos , Linfocitosis/inducido químicamente , Factor de Transcripción STAT3/genética , Ácido Selenioso/farmacología , Administración Oral , Animales , Antioxidantes/administración & dosificación , Arsénico/administración & dosificación , Arsénico/orina , Regulación hacia Abajo/efectos de los fármacos , Estimación de Kaplan-Meier , Hígado/patología , Masculino , Mesocricetus , Complejo de la Endopetidasa Proteasomal/genética , Complejo de la Endopetidasa Proteasomal/metabolismo , Factor de Transcripción STAT3/metabolismo , Ácido Selenioso/administración & dosificación , Aumento de Peso/efectos de los fármacos , alfa-Tocoferol/farmacología , alfa-Tocoferol/uso terapéuticoRESUMEN
Cadmium (Cd) contamination has generated an environmental problem worldwide, leading to harmful effects on human health and damages to plant metabolism. Selenium (Se) is non essential for plants, however it can improve plant growth and reduce the adverse effects of abiotic stress. In addition, ethylene may interplay the positive effects of Se in plants. In order to investigate the role of ethylene in Se-modulation of antioxidant defence system in response to Cd-stress, we tested the hormonal mutant Epinastic (epi) with a subset of constitutive activation of the ethylene response and Micro-Tom (MT) plants. For this purpose, Se mineral uptake, Cd and Se concentrations, pigments, malondialdeyde (MDA) and hydrogen peroxide (H2O2) contents, ethylene production, glutathione (GSH) compound, and superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GSH-Px) activities were analysed in MT and epi plants submitted to 0.5â¯mM CdCl2 and 1⯵M of selenate or selenite. MT plants treated with both Se forms increased growth in the presence or not of 0.5â¯mM CdCl2, but not change epi growth. Both Se forms reduced Cd uptake in MT plants and cause reverse effect in epi plants. P, Mg, S, K and Zn uptake increased in epi plants with Se application, irrespective to Cd exposure. Chlorophylls and carotenoids contents decreased in both genotypes under Cd exposure, in contrast to what was observed in epi leaves in the presence of Se. When antioxidant enzymes activities were concerned, Se application increased Mn-SOD, Fe-SOD and APX activities. In the presence of Cd, MT and epi plants exhibited decreased SOD activity and increased CAT, APX and GR activities. MT and epi plants with Se supply exhibited increased APX and GR activities in the presence of Cd. Overall, these results suggest that ethylene may be involved in Se induced-defence responses, that triggers a positive response of the antioxidant system and improve growth under Cd stress. These results showed integrative roles of ethylene and Se in regulating the cell responses to stressful-conditions and, the cross-tolerance to stress could be used to manipulate ethylene regulated gene expression to induce heavy metal tolerance.
Asunto(s)
Antioxidantes/metabolismo , Cadmio/efectos adversos , Etilenos/metabolismo , Estrés Oxidativo/efectos de los fármacos , Selenio/farmacología , Solanum lycopersicum/efectos de los fármacos , Adaptación Fisiológica , Ascorbato Peroxidasas/metabolismo , Cadmio/metabolismo , Catalasa/metabolismo , Exposición a Riesgos Ambientales , Glutatión/metabolismo , Glutatión Reductasa/metabolismo , Humanos , Peróxido de Hidrógeno/metabolismo , Solanum lycopersicum/metabolismo , Mutación , Oxidación-Reducción , Hojas de la Planta/metabolismo , Ácido Selénico/farmacología , Ácido Selenioso/farmacología , Selenio/metabolismo , Superóxido Dismutasa/metabolismoAsunto(s)
Babesia/efectos de los fármacos , Insulina/fisiología , Putrescina/farmacología , Ácido Selenioso/farmacología , Transferrina/farmacología , Animales , Babesia/crecimiento & desarrollo , Babesia/fisiología , Babesiosis/parasitología , Reactores Biológicos/parasitología , Bovinos , Medio de Cultivo Libre de Suero , Eritrocitos/parasitología , Técnicas In VitroRESUMEN
Human studies suggest that in utero exposure to arsenic results in adverse pregnancy outcomes. The use of dietary supplements, such as sodium selenite (SS) or α-tocopherol succinate (α-TOS), is a reasonable approach to ameliorate such health effects. Sodium arsenite at 100ppm was administered via drinking water to female hamsters from gestational days 1 or 8 to the time of delivery. Viable fetuses, fetal resorptions and non-viable fetuses were recorded during and after pregnancy and total arsenic and its metabolites were characterized in pregnant animals, placentas and fetuses. Arsenic was found to accumulate in the placenta and fetus, increasing fetal mortality, non-viable fetuses and resorptions. Co-administration of SS and α-TOS significantly reduced the observed teratogenic effects. SS influenced arsenic biotransformation by reducing the MMA/InAs index and increasing the DMA/MMA, whereas α-TOS more likely exerts its protective effect through its potent antioxidant activity.
Asunto(s)
Antioxidantes/farmacología , Arsenitos/toxicidad , Ácido Selenioso/farmacología , Compuestos de Sodio/toxicidad , Tocoferoles/farmacología , Animales , Arsenitos/orina , Encéfalo/metabolismo , Cricetinae , Suplementos Dietéticos , Femenino , Feto/efectos de los fármacos , Feto/metabolismo , Riñón/metabolismo , Intercambio Materno-Fetal , Placenta/metabolismo , Embarazo , Piel/metabolismo , Compuestos de Sodio/orina , Vejiga Urinaria/metabolismoRESUMEN
Breast cancer is a global public health problem and the most frequent cause of cancer death among women. Mammary carcinogenesis is driven not only by genetic alterations but also by epigenetic disturbances. Because epigenetic marks are potentially reversible they represent promising molecular targets for breast cancer prevention interventions. Selenium is a promising anti-breast cancer trace element that has shown the modulation of DNA methylation and histone post-translational modifications in other malignancies. This study aimed to evaluate the effects of selenium compounds [methylseleninic acid (MSA) and selenite] on cell proliferation and death, expression of the tumor suppressor gene RASSF1A and epigenetic marks in MCF-7 human breast adenocarcinoma cells. Treatment with MSA or selenite markedly inhibited (P<0.05) in a dose-dependent manner the proliferation of MCF-7 cells. MSA induced (P<0.05) G2/M cell arrest while selenite presented the opposite effect. Regarding cell death induction, MSA acted mainly by inducing apoptosis (P<0.05), while selenite only induced necrosis (P<0.05). Furthermore selenite, but not MSA, markedly induced (P<0.05) cytotoxicity and increased (P<0.05) RASSF1A expression. Both selenium compounds inhibited (P<0.05) DNMT1 expression. MSA decreased (P<0.05) H3K9me3 and increased (P<0.05) H4K16ac, while selenite decreased (P<0.05) this latter histone mark. To the best of our knowledge this is the first report showing that selenite and MSA modulate epigenetic marks specifically in breast cancer cells. Our data reinforce the anti-breast cancer potential of selenium that is dependent on its chemical form. Furthermore the data show that epigenetic mechanisms represent relevant molecular targets involved in selenium inhibitory effects in breast cancer cells.