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1.
Front Chem ; 6: 276, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30175092

RESUMO

The use of medicinal plants to counteract the oxidative damage in neurodegenerative diseases has steadily increased over the last few years. However, the rationale for using these natural compounds and their therapeutic benefit are not well explored. In this study, we evaluated the effect of different Physalis peruviana extracts on astrocytic cells (T98G) subjected to oxidative damage induced by rotenone. Extracts of fresh and dehydrated fruits of the plant with different polarities were prepared and tested in vitro. Our results demonstrated that the ethanolic extract of fresh fruits (EF) and acetone-dehydrated fruit extract (AD) increased cell viability, reduced the formation of reactive oxygen species (ROS) and preserved mitochondrial membrane potential. In contrast, we observed a significant reduction in mitochondrial mass when rotenone-treated cells were co-treated with EF and AD. These effects were accompanied by a reduction in the percentage of cells with fragmented/condensed nuclei and increased expression of endogenous antioxidant defense survival proteins such as ERK1/2. In conclusion, our findings suggest that ethanolic and acetone extracts from P. peruviana are potential medicinal plant extracts to overcome oxidative damage induced by neurotoxic compounds.

2.
Environ Mol Mutagen ; 50(9): 771-80, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19449395

RESUMO

Benzene is a widespread volatile compound and an environmental contaminant. Since it causes important toxic effects in workers exposed to low levels, long-term exposure to this compound has been extensively studied. Leukemia, blood disorders, bone marrow depression, and some types of cancer are directly related to benzene-initiated toxicity. Bioactivation of benzene can lead to the formation of hazardous metabolites such as phenol, hydroquinone, and catechol. Catechol forms semiquinones and reactive quinones that are presumed to play an important role in the generation of reactive oxygen species (ROS). ROS formation can directly induce single and double strand breaks in the DNA, oxidized nucleotides, and hyper-recombination, and consequently produces deleterious genetic changes. In this review, we have addressed the cytotoxic effects of benzene and its main metabolite, catechol, focusing on the oxidative pathway and further DNA damage.


Assuntos
Benzeno/toxicidade , Catecóis/farmacologia , Dano ao DNA , Radicais Livres , Estresse Oxidativo , Animais , Humanos
3.
Neurochem Res ; 34(2): 215-20, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18512151

RESUMO

Parkinson's disease (PD) is one of the most important neurodegenerative worldwide disorders. The potential cytoprotective effects of aqueous extract of Valeriana officinalis on rotenone-induced apoptosis in human neuroblastoma SH-SY5Y cells were demonstrated. The cytotoxicity, cell viability and analysis of cellular morphology were performed by MTT-tetrazole (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and phase contrast microscopy, respectively. Significant changes in the cellular morphology, and condensation of the cell body could be observed when cells were treated with 300 nM rotenone for 48 h. Three different concentrations of Valeriana officinalis extract were used (0.049, 0.098 and 0.195 mg/mL). These extracts brought about an increase of 7.0 +/- 1.3%, 14.5 +/- 1.3% and 14.5 +/- 3.2% in cell viability. Our results indicated that neuroprotector action of the Valeriana officinalis extract provides support for later studies as they help understanding this drug for the development of cytoprotective various therapies in PD.


Assuntos
Citoproteção , Doença de Parkinson/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Valeriana/química , Linhagem Celular Tumoral , Humanos
4.
Biocell ; 32(1): 1-8, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18669318

RESUMO

Cellular and subcellular organization and distribution of actin filaments have been studied with various techniques. The use of fluorescence photo-oxidation combined with phalloidin conjugates with eosin has allowed the examination of the precise cellular and subcellular location of F-actin. Correlative fluorescence light microscopy and transmission electron microscopy studies of F-actin distribution are facilitated with this method for morphological and physiological studies. Because phalloidin-eosin is smaller than other markers, this method allows the analysis of the three-dimensional location of F-actin with high-resolution light microscopy, three-d serial sections reconstructions, and electron tomography. The combination of selective staining and three-dimensional reconstructions provide a valuable tool for revealing aspects of the synaptic morphology that are not available when conventional electron microscopy is used. By applying this selective staining technique and three-dimensional imaging, we uncovered the structural organization of actin in the postsynaptic densities in physiological and pathological conditions.


Assuntos
Citoesqueleto de Actina/ultraestrutura , Sistema Nervoso Central/ultraestrutura , Corantes Fluorescentes/farmacologia , Imageamento Tridimensional/métodos , Citoesqueleto de Actina/metabolismo , Actinas/metabolismo , Animais , Sistema Nervoso Central/metabolismo , Amarelo de Eosina-(YS)/farmacologia , Humanos , Microscopia de Fluorescência/métodos , Modelos Moleculares , Oxirredução , Faloidina/farmacologia , Fótons , Coloração e Rotulagem/métodos
5.
Brain Res ; 1198: 188-96, 2008 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-18241847

RESUMO

Parkinson's disease (PD) is one of the most important neurodegenerative worldwide disorders. It is characterized by a selective and progressive degeneration of dopaminergic neurons, causing a series of symptoms which might ultimately induce programmed cell death. The potential cytoprotective effects of one of the commercial extracts of Anemopaegma mirandum (Catuaba), a Brazilian tree, on Rotenone-induced apoptosis in human neuroblastomas SH-SY5Y cells was demonstrated. The cell viability, analysis of cellular morphology, nuclei morphology and ultra structural research were done by MTT-tetrazole (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, phase contrast microscopy, stained with Hoechst 33258 and electron microscopy transmission, respectively. Three different concentrations of Catuaba extract were used (0.312, 0.625 and 1.250 mg/mL). These extracts promoted an increase of 22.3+/-3.6%, 22.0+/-2.1% and 15.8+/-0.7% on the cell viability. Notable changes in the cellular morphology, condensation of the cell body, nuclear fragmentation and condensation into discrete dense chromatin clumps were observed when the cells were treated with 300 nM Rotenone for 48 h. These effects were partially altered when the extract of A. mirandum was added to the Rotenone treatment. Ultra structural analysis by electron microscopy demonstrated that citoplasmatic membranes and mitochondria membrane were also clearly preserved in the group treated with the extract. Therefore, in this study, our findings indicated that extracts of A. mirandum have cytoprotective effects on Rotenone-induced apoptosis in human neuroblastomas SH-SY5Y cells.


Assuntos
Apoptose/efeitos dos fármacos , Degeneração Neural/tratamento farmacológico , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/tratamento farmacológico , Extratos Vegetais/farmacologia , Apoptose/fisiologia , Linhagem Celular Tumoral , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Citoproteção/efeitos dos fármacos , Citoproteção/fisiologia , Fragmentação do DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Membranas Intracelulares/efeitos dos fármacos , Membranas Intracelulares/patologia , Microscopia Eletrônica de Transmissão , Degeneração Neural/induzido quimicamente , Degeneração Neural/fisiopatologia , Neurônios/metabolismo , Neurônios/patologia , Neurotoxinas/antagonistas & inibidores , Neurotoxinas/toxicidade , Doença de Parkinson/metabolismo , Doença de Parkinson/fisiopatologia , Rotenona/antagonistas & inibidores , Rotenona/toxicidade , Sais de Tetrazólio , Tiazóis
6.
Neurochem Res ; 28(10): 1597-605, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14570406

RESUMO

ATP stimulates [Ca2+]i increases in midbrain synaptosomes via specific ionotropic receptors (P2X receptors). Previous studies have demonstrated the implication of P2X3 subunits in these responses, but additional P2X subunits must be involved. In the present study, ATP and BzATP proved to be able to induce intrasynaptosomal calcium transients in the midbrain synaptosomes, their effects being potentiated when assayed in a Mg2+-free medium. Indeed, BzATP was shown to be more potent than ATP, and their effects could be inhibited by PPADS and KN-62, but not by suramin. This activity profile is consistent with the presence of functional P2X7 receptors in the midbrain terminals. The existence of presynaptic responses to selective P2X7 agonists could be confirmed by means of a microfluorimetric technique allowing [Ca2+]i measurements in single synaptic terminals. Additionally, the P2X7 receptor protein could be identified in the midbrain synaptosomes and in axodendritic prolongations of cerebellar granule cells by immunochemical staining.


Assuntos
Trifosfato de Adenosina/análogos & derivados , Encéfalo/metabolismo , Receptores Purinérgicos P2/metabolismo , Sinaptossomos/metabolismo , Trifosfato de Adenosina/farmacologia , Animais , Encéfalo/citologia , Encéfalo/ultraestrutura , Cerebelo/citologia , Cerebelo/metabolismo , Dendritos/metabolismo , Relação Dose-Resposta a Droga , Imuno-Histoquímica , Técnicas In Vitro , Magnésio/metabolismo , Masculino , Mesencéfalo/citologia , Mesencéfalo/metabolismo , Mesencéfalo/ultraestrutura , Antagonistas do Receptor Purinérgico P2 , Ratos , Ratos Wistar , Receptores Purinérgicos P2X7
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