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An all-fiber integrated device capable of separating and counting particles is presented. A sequence of silica fiber capillaries with various diameters and longitudinal cavities are used to fabricate the component for size-based elasto-inertial passive separation of particles followed by detection in an uninterrupted continuous flow. Experimentally, fluorescent particles of 1 µm and 10 µm sizes are mixed in a visco-elastic fluid and fed into the all-fiber separation component. The particles are sheathed by an elasticity enhancer (PEO - polyethylene oxide) to the side walls. Larger 10 µm particles migrate to the center of the silica capillary due to the combined inertial lift force and elastic force, while the smaller 1 µm particles are unaffected, and exit from a side capillary. A separation efficiency of 100% for the 10 µm and 97% for the 1 µm particles is achieved at a total flow rate of 50 µL min-1. To the best of our knowledge, this is the first time effective inertial-based separation has been demonstrated in circular cross-section microchannels. In the following step, the separated 10 µm particles are routed through another all-fiber component for counting and a counting throughput of â¼1400 particles per min is demonstrated. We anticipate the ability to combine high throughput separation and precise 3D control of particle position for ease of counting will aid in the development of advanced microflow cytometers capable of particle separation and quantification for various biomedical applications.
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We report a directly modulated distributed feedback laser operating in gain-switching mode for preparing the coherent states required for the Gaussian-modulated coherent-state (GMCS) continuous-variable quantum key distribution (CV-QKD) protocol. The proposed single-component quantum transmitter design eliminates the need for external modulators, decreasing the complexity of GMCS CV-QKD systems. The experimental results demonstrate a potential asymptotic secret key rate value of 2.63 Mbps over an 11-km fiber link, making the directly modulated GMCS transmitter particularly suitable for metropolitan optical networks where compactness, robustness, and low cost are key desirable features.
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Objective: To characterize rest-activity rhythm in chronic migraine (CM) and to investigate the relationship between this rhythm and depressive and anxiety symptoms in patients with CM. Methods: This was a study of adults aged 20 to 40 years. The rest-activity rhythm of patients with CM (n=23) and non-headache controls (NH, n=23) was assessed by actigraphy for 15 days, and they completed the following assessments: Visual Analogue Scale for pain intensity; Headache Diary; Headache Impact Test-6; Morningness-Eveningness Questionnaire; Pittsburgh Sleep Quality Index; Epworth Sleepiness Scale; Beck Depression Inventory; and State-Trait Anxiety Inventory. Results: Patients with CM showed less activity over 24 hours and more fragmented sleep. Reduced interdaily stability of the rest-activity rhythm was observed, with less robustness of this rhythm in the CM group. Multiple linear regressions revealed a significant association between the rest-activity rhythm and trait anxiety variables in patients with CM, specifically regarding the relative amplitude of the cycle, activity throughout 24 hours and during sleep, and robustness of the rest-activity rhythm. Conclusions: Our findings provide evidence that the robustness of the rest-activity rhythm, activity throughout 24 hours, and sleep fragmentation are associated with trait anxiety in patients with CM. Clinical trial registration: Brazilian Clinical Trials Registry (registration number: RBR-4M5J4S).
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OBJECTIVE: To characterize rest-activity rhythm in chronic migraine (CM) and to investigate the relationship between this rhythm and depressive and anxiety symptoms in patients with CM. METHODS: This was a study of adults aged 20 to 40 years. The rest-activity rhythm of patients with CM (n=23) and non-headache controls (NH, n=23) was assessed by actigraphy for 15 days, and they completed the following assessments: Visual Analogue Scale for pain intensity; Headache Diary; Headache Impact Test-6; Morningness-Eveningness Questionnaire; Pittsburgh Sleep Quality Index; Epworth Sleepiness Scale; Beck Depression Inventory; and State-Trait Anxiety Inventory. RESULTS: Patients with CM showed less activity over 24 hours and more fragmented sleep. Reduced interdaily stability of the rest-activity rhythm was observed, with less robustness of this rhythm in the CM group. Multiple linear regressions revealed a significant association between the rest-activity rhythm and trait anxiety variables in patients with CM, specifically regarding the relative amplitude of the cycle, activity throughout 24 hours and during sleep, and robustness of the rest-activity rhythm. CONCLUSIONS: Our findings provide evidence that the robustness of the rest-activity rhythm, activity throughout 24 hours, and sleep fragmentation are associated with trait anxiety in patients with CM.
Assuntos
Ritmo Circadiano , Transtornos de Enxaqueca , Adulto , Humanos , Sono , Descanso , AnsiedadeRESUMO
We present a versatile transmitter capable of performing both discrete variable and continuous variable quantum key distribution protocols (DV-QKD and CV-QKD, respectively). Using this transmitter, we implement a time-bin encoded BB84 DV-QKD protocol over a physical quantum channel of 47 km and a GG02 CV-QKD protocol with true local oscillator over a 10.5 km channel, achieving secret key rates of 4.1 kbps and 1 Mbps for DV- and CV-QKD, respectively. The reported transmitter scheme is particularly suitable for re-configurable optical networks where the QKD protocol is selected to optimize the performance according to the parameters of the links.
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We report a plug-and-play continuous variable quantum key distribution system (CV-QKD) with Gaussian modulated quadratures and a true local oscillator. The proposed configuration avoids the need for frequency locking two narrow line-width lasers. To minimize Rayleigh back-scattering, we utilize two independent fiber strands for the distribution of the laser and the transmission of the quantum signals. We further demonstrate the quantum-classical co-existing capability of our system by injecting high-power classical light in both fibers. A secret key rate up to 0.88 Mb/s is obtained by using two fiber links of 13 km and up to 0.3 Mb/s when adding 4 mW of classical light in the optical fiber used for transmitting the quantum signal. The reported performance indicates that the proposed QKD scheme has the potential to become an effective low-cost solution for metropolitan optical networks.
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The aim of this work was to study the antitumor effects and the mechanisms of toxic action of a series of 6-methoxyquinoline (6MQ) complexes in vitro. The Cu(II) and Zn(II) complexes (Cu6MQ and Zn6MQ) are formulated as M(6MQ)2Cl2; the Co(II) and Ag(I) compounds (Co6MQ and Ag6MQ) are ionic with formulae [Ag(6MQ)2]+NO3- and H(6MQ)+[Co(6MQ)Cl3]- (where H(6MQ)+ is the protonated ligand). We found that the copper complex, outperformed the Co(II), Zn(II) and Ag(I) complexes with a lower IC50 (57.9 µM) in A549 cells exposed for 24 h. Cu6MQ decreased cell proliferation and induced oxidative stress detected with H2DCFDA at 40 µM, which reduces GSH/GSSG ratio. This redox imbalance induced oxidative DNA damage revealed by the Micronucleus test and the Comet assay, which turned into a cell cycle arrest at G2/M phase and induced apoptosis. In multicellular spheroids, the IC50 values tripled the monolayer model (187.3 µM for 24 h). At this concentration, the proportion of live/dead cells diminished, and the spheroids could not proliferate or invade. Although Zn6MQ also decreased GSH/GSSG ratio from 200 µM and the cytotoxicity is related to oxidative stress, the induction of the hydrogen peroxide levels only doubled the control value. Zn6MQ induced S phase arrest, which relates with the increased micronucleus frequency and with the induction of necrosis. Finally, our results reveal a synergistic activity with a 1:1 ratio of both complexes in the monolayer and multicellular spheroids.
Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Quinolinas/farmacologia , Esferoides Celulares/efeitos dos fármacos , Células A549 , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Estresse Oxidativo/efeitos dos fármacos , Quinolinas/química , Esferoides Celulares/patologia , Relação Estrutura-AtividadeRESUMO
Flow cytometry is currently the gold standard for analysis of cells in the medical laboratory and biomedical research. Fuelled by the need of point-of-care diagnosis, a significant effort has been made to miniaturize and reduce cost of flow cytometers. However, despite recent advances, current microsystems remain less versatile and much slower than their large-scale counterparts. In this work, an all-silica fibre microflow cytometer is presented that measures fluorescence and scattering from particles and cells. It integrates cell transport in circular capillaries and light delivery by optical fibres. Single-stream cell focusing is performed by Elasto-inertial microfluidics to guarantee accurate and sensitive detection. The capability of this technique is extended to high flow rates (up to 800 µl/min), enabling a throughput of 2500 particles/s. The robust, portable and low-cost system described here could be the basis for a point-of-care flow cytometer with a performance comparable to commercial systems.
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A long-standing problem in quantum mechanics is the minimum number of observables required for the characterization of unknown pure quantum states. The solution to this problem is especially important for the developing field of high-dimensional quantum information processing. In this work we demonstrate that any pure d-dimensional state is unambiguously reconstructed by measuring five observables, that is, via projective measurements onto the states of five orthonormal bases. Thus, in our method the total number of different measurement outcomes (5d) scales linearly with d. The state reconstruction is robust against experimental errors and requires simple postprocessing, regardless of d. We experimentally demonstrate the feasibility of our scheme through the reconstruction of eight-dimensional quantum states, encoded in the momentum of single photons.
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Vanadium compounds were studied during recent years to be considered as a representative of a new class of nonplatinum metal antitumor agents in combination to its low toxicity. On the other hand, flavonoids are a wide family of polyphenolic compounds synthesized by plants that display many interesting biological effects. Since coordination of ligands to metals can improve the pharmacological properties, we report herein, for the first time, a exhaustive study of the mechanisms of action of two oxidovanadium(IV) complexes with the flavonoids: silibinin Na2[VO(silibinin)22]·6H2O (VOsil) and chrysin [VO(chrysin)2EtOH]2(VOchrys) on human colon adenocarcinoma derived cell line HT-29. The complexes inhibited the cell viability of colon adenocarcinoma cells in a dose dependent manner with a greater potency than that the free ligands and free metal, demonstrating the benefit of complexation. The decrease of the ratio of the amount of reduced glutathione to the amount of oxidized glutathione were involved in the deleterious effects of both complexes. Besides, VOchrys caused cell cycle arrest in G2/M phase while VOsil activated caspase 3 and triggering the cells directly to apoptosis. Moreover, VOsil diminished the NF-kB activation via increasing the sensitivity of cells to apoptosis. On the other hand, VOsil inhibited the topoisomerase IB activity concluding that this is important target involved in the anticancer vanadium effects. As a whole, the results presented herein demonstrate that VOsil has a stronger deleterious action than VOchrys on HT-29 cells, whereby suggesting that Vosil is the potentially best candidate for future use in alternative anti-tumor treatments.
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Neoplasias do Colo/tratamento farmacológico , Complexos de Coordenação/química , Flavonoides , Silimarina , Vanádio , Adenocarcinoma/tratamento farmacológico , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Complexos de Coordenação/farmacologia , Flavonoides/química , Humanos , Estrutura Molecular , Silibina , Silimarina/química , Vanádio/químicaRESUMO
Polyoxometalates (POMs) are early transition metal oxygen anion clusters. They display interesting biological effects mainly related to their antiviral and antitumor properties. On the other hand, copper compounds also show different biological and pharmacological effects in cell culture and in animal models. We report herein for the first time, a detailed study of the mechanisms of action of a copper(II) compound of the group of HPOMs with the formula K7Na3[Cu4(H2O)2(PW9034)2]20H2O (PW9Cu), in a model of human osteosarcoma derived cell line, MG-63. The compound inhibited selectively the viability of the osteosarcoma cells in the range of 25-100µM (p<0.01). Besides, we have clearly shown a more deleterious action of PW9Cu on tumor osteoblasts than in normal cells. Cytotoxicity studies also showed deleterious effects for PW9Cu. The increment of reactive oxygen species (ROS) and the decrease of the GSH/GSSG ratio were involved in the antiproliferative effects of PW9Cu. Moreover, the compound caused cell cycle arrest in G2 phase, triggering apoptosis as determined by flow cytometry. As a whole, these results showed the main mechanisms of the deleterious effects of PW9Cu in the osteosarcoma cell line MG-63, demonstrating that this compound is a promissory agent for cancer treatments.
Assuntos
Antineoplásicos/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Complexos de Coordenação/farmacologia , Cobre/farmacologia , Osteossarcoma/tratamento farmacológico , Óxidos/farmacologia , Compostos de Tungstênio/farmacologia , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/química , Cobre/química , Fragmentação do DNA , Glutationa/metabolismo , Humanos , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Estresse Oxidativo/efeitos dos fármacos , Óxidos/química , Fosfatidilserinas/metabolismo , Compostos de Tungstênio/químicaRESUMO
Flavonoids are a large family of polyphenolic compounds synthesized by plants. They display interesting biological effects mainly related to their antioxidant properties. On the other hand, vanadium compounds also exhibit different biological and pharmacological effects in cell culture and in animal models. Since coordination of ligands to metals can improve or change the pharmacological properties, we report herein, for the first time, a detailed study of the mechanisms of action of an oxidovanadium(IV) complex with the flavonoid silibinin, Na2[VO(silibinin)2]·6H2O (VOsil), in a model of the human osteosarcoma derived cell line MG-63. The complex inhibited the viability of osteosarcoma cells in a dose-dependent manner with a greater potency than that of silibinin and oxidovanadium(IV) (p < 0.01), demonstrating the benefit of complexation. Cytotoxicity and genotoxicity studies also showed a concentration effect for VOsil. The increase in the levels of reactive oxygen species and the decrease of the ratio of the amount of reduced glutathione to the amount of oxidized glutathione were involved in the deleterious effects of the complex. Besides, the complex caused cell cycle arrest and activated caspase 3, triggering apoptosis as determined by flow cytometry. As a whole, these results show the main mechanisms of the deleterious effects of VOsil in the osteosarcoma cell line, demonstrating that this complex is a promising compound for cancer treatments.
Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Osteossarcoma/tratamento farmacológico , Silimarina/farmacologia , Vanadatos/farmacologia , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Complexos de Coordenação/química , Humanos , Osteossarcoma/patologia , Silibina , Silimarina/química , Vanadatos/químicaRESUMO
We report herein the antitumor actions of three oxidovanadium(IV) complexes on MG-63 human osteosarcoma cell line. The three complexes: VO(oda), VO(oda)bipy and VO(oda)phen (oda=oxodiacetate), caused a concentration dependent inhibition of cell viability. The antiproliferative action of VO(oda)phen could be observed in the whole range of concentrations (at 2.5 µM), while VO(oda)bipy and VO(oda) showed a decrease of cell viability only at higher concentrations (at 50 and 75 µM, respectively) (p<0.01). Moreover, VO(oda)phen caused a decrease of lysosomal and mitochondrial activities at 2.5 µM, while VO(oda) and VO(oda)bipy affected neutral red uptake and mitochondrial metabolism at 50 µM (p<0.01). On the other hand, no DNA damage studied by the Comet assay could be observed in MG-63 cells treated with VO(oda) at 2.5-10 µM. Nevertheless, VO(oda)phen and VO(oda)bipy induced DNA damage at 2.5 and 10 µM, respectively (p<0.01). The generation of reactive oxygen species increased at 10 µM of VO(oda)phen and only at 100 µM of VO(oda) and VO(oda)bipy (p<0.01). Besides, VO(oda)phen and VO(oda)bipy triggered apoptosis as determined by externalization of the phosphatidylserine. The determination of DNA cleavage by agarose gel electrophoresis showed that the ability of VO(oda)(bipy) is similar to that of VO(oda), while VO(oda)(phen) showed the highest nuclease activity in this series. Overall, our results showed a good relationship between the bioactivity of the complexes and their structures since VO(oda)phen presented the most potent antitumor action in human osteosarcoma cells followed by VO(oda)bipy and then by VO(oda) according to the number of intercalating heterocyclic moieties.
Assuntos
2,2'-Dipiridil/química , Acetatos/química , Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Fenantrolinas/química , Vanádio/química , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa , Complexos de Coordenação/síntese química , Fragmentação do DNA/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Vermelho Neutro/metabolismo , Fosfatidilserinas/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
The secure transfer of information is an important problem in modern telecommunications. Quantum key distribution (QKD) provides a solution to this problem by using individual quantum systems to generate correlated bits between remote parties, that can be used to extract a secret key. QKD with D-dimensional quantum channels provides security advantages that grow with increasing D. However, the vast majority of QKD implementations has been restricted to two dimensions. Here we demonstrate the feasibility of using higher dimensions for real-world quantum cryptography by performing, for the first time, a fully automated QKD session based on the BB84 protocol with 16-dimensional quantum states. Information is encoded in the single-photon transverse momentum and the required states are dynamically generated with programmable spatial light modulators. Our setup paves the way for future developments in the field of experimental high-dimensional QKD.
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Flavonoids, a polyphenolic compound family, and the vanadium compounds have interesting biological, pharmacological, and medicinal properties. We report herein the antitumor actions of the complex [VO(chrysin)2EtOH]2 (VOchrys) on the MG-63 human osteosarcoma cell line. Oxovanadium(IV), chrysin and VOchrys caused a concentration-dependent inhibition of cell viability. The complex was the strongest antiproliferative agent (p < 0.05). Cytotoxicity and genotoxicity studies also showed a concentration effect. Reactive oxygen species (ROS) and the alterations in the GSH/GSSG ratio underlie the main mechanisms of action of VOchrys. Additions of ROS scavengers (vitamin C plus vitamin E) or GSH to the viability experiments demonstrated beneficial effects (p < 0.01). Besides, the complex triggered apoptosis, disruption of the mitochondria membrane potential (MMP), increased levels of caspase 3 and DNA fragmentation measured by the sub-G1 peak in cell cycle arrest experiments (p < 0.01). Collectively, VOchrys is a cell death modulator and a promissory complex to be used in cancer treatments.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Flavonoides/química , Compostos Organometálicos/farmacologia , Osteossarcoma/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Vanadatos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Osteossarcoma/patologia , Relação Estrutura-AtividadeRESUMO
We report the experimental implementation of a new method for generating multiple dynamical optical tweezers, where each one of them is generated with an independent linear polarization state with arbitrary orientation. This also allows an independent simultaneous polarization-rotation control. The laser beam, both for generating multiple traps and polarization control, has been modulated using a single reflective nematic liquid crystal with parallel alignment. We present experimental results of controlled displacement, orientation and rotation of birefringent particles. In addition, a simple method for estimating and canceling out the primary astigmatism present in the system is presented.
Assuntos
Biofísica/métodos , Birrefringência , Holografia/instrumentação , Pinças Ópticas , Rotação , Algoritmos , DNA/química , Dimerização , Desenho de Equipamento , Holografia/métodos , Cristais Líquidos , Óptica e Fotônica/métodos , Tamanho da Partícula , Estresse Mecânico , Raios UltravioletaRESUMO
Norfloxacin is a fluoroquinolone antibiotic used in the treatment of bacterial infections. In this article, we studied the potential antitumoral action of a complex of Norfloxacin with Cu(II), Cu(Nor)(2)·5H(2)O on osteosarcoma cells (UMR106) and calvaria-derived cells (MC3T3-E1), evaluating its cytotoxicity and genitoxicity. We have also elucidated the more stable conformation of this complex under physiologic conditions by Molecular Dynamic simulations based on the model of the canonical ensemble and PM6 force field. When solvent effect was taken into account, the complex conformation with both carbonyl groups in opposite sides displayed lower energy. Cu(Nor)(2)·5H(2)O caused an inhibitory effect on the proliferation on both cell lines from 300 µM (P < 0.01). Nevertheless, the decline on cell proliferation of UMR106 cells was more pronounced (45 % vs basal) than in MC3T3-E1 cells (20 % vs basal) at 300 µM (P < 0.01). Cu(Nor)(2)·5H(2)O altered lysosomal metabolism (Neutral Red assay) in a dose-dependent manner from 300 µM (P < 0.001). Morphological studies showed important transformations that correlated with a decrease in the number of cells in a dose-dependent manner. Moreover, Cu(Nor)(2)·5H(2)O caused statistically significant genotoxic effects on both osteoblast cell lines in a lower range of concentrations (Micronucleus assay) (P < 0.05 at 10 µM, P < 0.001 from 25 to 50 µM). UMR106 cells displayed a dose-related genotoxic effect between 5 and 25 µM while the MC3T3-E1 cells showed a narrower concentration dependent range. Altogether, these results suggest that Cu(Nor)(2)·5H(2)O is a good candidate to be further evaluated for alternative therapeutics in cancer treatment.
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Antineoplásicos/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Complexos de Coordenação/farmacologia , Cobre/química , Osteossarcoma/tratamento farmacológico , Animais , Antineoplásicos/química , Antineoplásicos/toxicidade , Neoplasias Ósseas/patologia , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Cobre/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Lisossomos/efeitos dos fármacos , Camundongos , Testes para Micronúcleos , Simulação de Dinâmica Molecular , Testes de Mutagenicidade , Norfloxacino/síntese química , Norfloxacino/química , Norfloxacino/farmacologia , Osteoblastos/efeitos dos fármacos , Osteossarcoma/patologia , RatosRESUMO
Vanadium is a trace element present in practically all cells in plants and animals. While the essentiality of vanadium for human beings remains to be well established, vanadium has become an increasingly important environmental metal. Vanadium compounds exert a variety of biological activities and responses. At pharmacological doses, vanadium compounds display relevant biological actions such as insulin and growth factor mimetic or enhancing effects, as well as osteogenic and cardioprotective activity. On the other hand, depending on the nature of compounds and their concentrations, toxicological actions and adverse side effects may also be shown. Nevertheless, the toxic effects may be useful to develop new antitumoral drugs. In this review, the authors summarize current knowledge and new advances on in vitro and in vivo effects of inorganic and organically-chelated vanadium compounds. The effects of vanadium derivatives on some cellular signaling pathways related to different diseases are compiled. In particular, the pathways relevant to the insulin mimetic, osteogenic, cadioprotective and antitumoral actions of vanadium compounds have been comprehensively reviewed. The knowledge of these intracellular signaling pathways may facilitate the rational design of new vanadium compounds with promising therapeutic applications as well as the understanding of secondary side effects derived from the use of vanadium as a therapeutic agent.
Assuntos
Hipoglicemiantes/uso terapêutico , Compostos de Vanádio/farmacologia , Compostos de Vanádio/uso terapêutico , Vanádio/farmacologia , Animais , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Glicemia/metabolismo , Cardiotônicos/metabolismo , Cardiotônicos/farmacologia , Cardiotônicos/uso terapêutico , Quelantes , Feminino , Humanos , Hipoglicemiantes/farmacologia , Insulina/metabolismo , Osteogênese/efeitos dos fármacos , Osteogênese/fisiologia , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Vanádio/fisiologia , Compostos de Vanádio/metabolismoRESUMO
Strong chelating ligands as oxodiacetate (oda) are model systems to study the process of metal trapping by living organisms. Vanadium compounds display interesting biological and pharmacological actions. In vertebrates, vanadium is stored mainly in bones. In the present study we report the effects of the complex of oda with vanadyl(IV) cation, VO(oda), on two osteoblast cell lines, one normal (MC3T3E1) and the other tumoral (UMR106). VO(oda) exerted cytotoxic actions in osteoblasts as it was determined through a dose-dependent decrease in cell proliferation, and morphological and actin alterations. The putative mechanisms underlying VO(oda) deleterious effects were also investigated. The complex increased the level of ROS which correlated with a decreased in GSH/GSSG ratio. Besides, VO(oda) induced a dissipation of the mitochondria membrane potential (MMP) and promoted an increase in ERK cascade phosphorylation, which is involved in the regulation of cellular death and survival. All the effects were more pronounced in MC3T3-E1 than in UMR106 cells. ERK activation was inhibited by PD98059, Wortmanin and the ROS scavenger NAC (N-acetyl cysteine). These results suggest that VO(oda) stimulated ERKs phosphorilation by induction of free radicals involving kinases upstream of ERK pathway. The inhibitory effect of the complex on cell proliferation was partially reversed in both cell lines by NAC. Moreover, PD98059 and Wortmanin also partially reversed the inhibition of cell proliferation in the tumoral osteoblasts. The use of specific inhibitors and ROS scavengers suggested the involvement of oxidative stress, MMP alterations and ERK pathway in the apoptotic actions of this complex.
Assuntos
Citotoxinas/química , Citotoxinas/farmacologia , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Osteoblastos/efeitos dos fármacos , Oxigênio/química , Vanádio/química , Actinas/metabolismo , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Ativação Enzimática/efeitos dos fármacos , Glutationa/metabolismo , Dissulfeto de Glutationa/metabolismo , Espaço Intracelular/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Vermelho Neutro , Osteoblastos/citologia , Osteoblastos/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismoRESUMO
The potassium salt of the carbonato oxodiperoxovanadate(V) complex, obtained by a known synthetic procedure, was thoroughly characterized by infrared, Raman, and electronic spectroscopy. The bioactivity of the complex on the cell proliferation was tested on osteoblast-like cells (MC3T3E1 osteoblastic mouse calvaria-derived cells and UMR106 rat osteosarcoma-derived cells) in culture. At low doses, the complex is more toxic for the nontransformed osteoblasts than for the tumoral ones, whereas at higher doses the deleterious effects are similar for both cell lines. This peroxo complex seems to be the most toxic compound that has so far been tested on osteoblast-like cells in culture.