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1.
Eur Rev Med Pharmacol Sci ; 15(2): 181-91, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21434485

RESUMO

AIM: To verify the involvement of free radicals in tumor progression and to investigate the effects of an ethanolic extract of Ruta Chalepensis L. and of rutin in blood of patients with colon cancer. MATERIALS AND METHODS: Leaves of Ruta Chalepensis L. were collected in the area around Catania (Italy). For the preparation of the ethanol extract of leaves, an exhaustive extraction of 100 g of the drug was carried out in Soxhlet with 800 ml of 95% ethanol. Fifty-six patients with colorectal cancer were randomly selected for this study; among these, 34 were affected by an early stage (T1 N0 M0 according to scale), while 22 were affected by an advanced stage (T4, N1-2, M0) of cancer. Data obtained from these patients were compared with those of a control group consisting of 20 healthy subjects. Plasma of each sample was used for determining non-proteic antioxidant capacity, thiol groups, lipid hydroperoxides and nitrite/nitrate levels, evaluated by spectrophotometric tests. In addition, percentage of haemolysis was evaluated incubating (for 2 hours at 37 degrees C) erythrocyte suspension with a free radical donor (50 mM 2,2'-azobis-amidino propane chloridrate), in the presence or absence of ethanolic extract of Ruta Chalepensis L. (250 microg/ml) or rutin (1 mM). RESULTS: Non-proteic antioxidant capacity was significantly lower in cancerous patients than in healthy subjects (p < 0.001). This decrease was stage-related. In fact, non-proteic antioxidant capacity resulted lower in advanced than in early colorectal cancer (p < 0.001). The same significant stage-related decrease was observed in plasma thiol groups (p < 0.001). Coherently with the decrease in non-proteic antioxidant capacity and thiol groups, higher levels of lipid hydroperoxides and nitrite/nitrate were observed in patients with colorectal cancer with respect to healthy subjects (p < 0.001) and the increase in these markers of oxidative stress was related to the cancer stadiation. Neoplastic patients also showed an increased percentage of oxidative hemolysis respect to controls and the haemolytic damage was correlated with the stage of colon cancer. Both the extract of Ruta Chalepensis L. and rutin were able to protect erythrocytes from oxidative stress induced by the free radical donor, but the extract of Ruta Chalepensis L. was more effective than rutin. This protective effect was significant only in erythrocytes from patients with early colorectal group, whereas no significant modification was induced by Ruta Chalepensis L. or rutin in red blood cells from advanced colorectal cancer patients exposed to the same experimental conditions. CONCLUSION: Oxidative stress correlates with colon cancer stadiation and both the extract of Ruta chalepensis and rutin are able to protect red blood cells from radical-induced damage. However, their effects are significant in early stages of cancer. So these natural antioxidants might be usefull to prevent carcinogenesis and/or tumor progression.


Assuntos
Antioxidantes/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Ruta , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo
2.
J Neurosci Res ; 86(6): 1297-305, 2008 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-18041095

RESUMO

Type-2 transglutaminase (TG-2) is a multifunctional enzyme involved in the regulation of cell differentiation and survival that recently has been shown to play an emerging role in astrocytes, where it is involved in both proliferation and differentiation processes. Growth factors (GFs) such as EGF, basic fibroblast growth factor, insulin-like growth factor-I (IGF-I), and insulin (INS) are trophic and mitogenic peptides that participate in neuron-glia interactions and stimulate neuronal and astroglial proliferation and differentiation. Steroid hormones such as glucocorticoids and estrogens also play a pivotal role in neuronal and astroglial proliferation and differentiation and are key hormones in neurodegenerative and neuroprotective processes. We investigated the effects of the interaction of GFs with dexamethasone (DEX) or 17beta-estradiol (E(2)) on TG-2 activity and their expression in cultured astrocytes. We observed a significant increase in TG-2 activity and expression in astroglial cells treated for 24 hr with IGF-I, EGF, or INS. Priming of the cells with DEX or E(2), for 48 hr also led to an increase in TG-2 levels. When growth factors were present in the last 24 hr of the steroid treatment, a reduction in TG-2 expression and activity and a different subcellular TG-2 distribution were found. Our data indicate that steroid hormone-GF interaction may play an important role in astroglial function. The effect on TG-2 could be part of the regulation of intracellular pathways associated with the astrocyte response observed in physiological conditions and, possibly, also in neuropathological diseases.


Assuntos
Astrócitos/metabolismo , Dexametasona/metabolismo , Estradiol/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Transglutaminases/metabolismo , Animais , Western Blotting , Células Cultivadas , Imunofluorescência , Microscopia Confocal , Proteína 2 Glutamina gama-Glutamiltransferase , Ratos , Esteroides/metabolismo
3.
Neurochem Res ; 33(12): 2601-8, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18841472

RESUMO

Effects of acetylcholine and of the cholinergic precursors choline, cytidine 5'-diphosphocholine (CDP-choline) and alpha-glyceryl-phosphorylcholine (alpha-GPC) on transglutaminase (TG) and cyclin D1 expression were studied in primary astrocyte cultures by confocal laser microscopy (CLSM) with monodansyl-cadaverine uptake as a marker of enzyme activity and by immunochemistry (Western blotting). CLSM analysis showed an increased cytofluorescence in 0.1 microM choline-treated astrocytes. Treatment with CDP-choline dose-dependently increased TG. A total of 1 microM CDP-choline exposure in 14 days in vitro (DIV) astrocyte cultures increased cytofluorescence. A total of 1 microM alpha-GPC 24 h-treated cultures revealed increased cytofluorescence both in cytosol and nuclei. Western blot analysis showed an increased TG expression in cultures exposed for 24 h to 1 microM choline or alpha-GPC, whereas in 24 h 1 microM CDP-choline and acetylcholine-treated astrocytes TG expression was unaffected. Treatment with 1 microM acetylcholine reduced TG expression at 21 DIV. In cultures at 14 and 35 DIV cholinergic precursor treatment for 24 h induced a marked down-regulation of cyclin D1 expression, with reduced cyclin D1 expression in 1 microM alpha-GPC treated astrocytes. Our data suggest a role of cholinergic precursors investigated independent from acetylcholine on maturation and differentiation of astroglial cells in vitro, rather than on their growth, proliferation and development in culture.


Assuntos
Acetilcolina/farmacologia , Astrócitos/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Acetilcolina/química , Animais , Astrócitos/citologia , Western Blotting , Células Cultivadas , Ratos , Ratos Wistar
4.
Clin Exp Hypertens ; 30(8): 798-807, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19021029

RESUMO

The aim of the present investigation was to study the effects of choline and choline-containing phospholipids CDP-choline (CDPC) and L-alpha-glyceryl-phosphorylcholine (AGPC) on transglutaminase (TG) activity and expression in primary astrocyte cultures. TG is an important Ca(2+)-dependent protein that represents a normal constituent of nervous systems during fetal stages of development, playing a role in cell signal transduction, differentiation, and apoptosis. Confocal laser scanning microscopy (CLSM) analysis showed an increase of TG activity in astrocyte cultures treated with choline, CDPC, or AGPC at 0.1 microM or 1 microM concentrations. Comparatively, AGPC induced the most conspicuous effects enhancing monodansyl-cadaverine fluorescence both in cytosol and in nuclei, supporting the evidence of the important role played by AGPC throughout differentiation processes tightly correlated to nucleus-cytosol cross- talk during astroglial cells proliferation and development. Western blot analysis showed that in 24h 1 microM AGPC and choline-treated astrocytes increased TG-2, whereas no effect was observed in 24h 1 microM CDP-choline treated astrocytes. Our data suggest a crucial role of choline precursors during different stages of astroglial cell proliferation and differentiation in cultures.


Assuntos
Astrócitos/enzimologia , Citidina Difosfato Colina/farmacologia , Glicerilfosforilcolina/farmacologia , Nootrópicos/farmacologia , Transglutaminases/metabolismo , Animais , Apoptose/efeitos dos fármacos , Astrócitos/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Ratos , Ratos Wistar
5.
Life Sci ; 78(13): 1401-6, 2006 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-16457855

RESUMO

Many environmental, physiological and genetic factors have been implicated in defective sperm function, the most common cause of infertility. In addition, sperm preparation techniques such as centrifugation, used prior to in vitro fertilization, are associated with the generation of reactive oxygen species (ROS) and an increase in the level of DNA damage. Factors that can offer spermatozoa protection are, therefore, of great importance. This study was designed to examine in vitro the effect of a Chilean propolis ethanolic extract on human spermatozoa treated with benzo[a]pyrene and exogenous reactive oxygen species. Our experimental evidence demonstrated that the natural drug under investigation is able to protect genomic DNA by damage induced by benzo[a]pyrene, hydrogen peroxide (H2O2) and hydrogen peroxide in combination with adenosine 5'-diphosphate (ADP) and ferrous sulfate (FeSO4), determining a significant reduction of the intracellular oxidants. An increase in membrane damage, measured by monitoring the formation of thiobarbituric acid-reactive substances (TBARS) and lactic dehydrogenase (LDH) release, was observed only in sperm treated with H2O2, ADP and FeSO4. The propolis extract was shown to possess the capacity to protect sperm membrane from the deleterious action of oxidative attack, reducing TBARS formation and LDH release. In summary, our results evidence that the protective effect exhibited by this natural compound in human spermatozoa is correlated, at least in part, to the antioxidant capacity of its active components, and suggest that propolis may have a role in protection against male infertility.


Assuntos
Benzo(a)pireno/toxicidade , Dano ao DNA/efeitos dos fármacos , Própole/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Espermatozoides/fisiologia , Difosfato de Adenosina/farmacologia , Etanol , Compostos Ferrosos/farmacologia , Humanos , L-Lactato Desidrogenase , Masculino , Malondialdeído/metabolismo , Extratos Vegetais/farmacologia , Espermatozoides/efeitos dos fármacos , Espermatozoides/patologia
6.
FEBS Lett ; 578(1-2): 80-4, 2004 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-15581620

RESUMO

The aim of this study was to evaluate the involvement of oxidative stress in glutamate-evoked transglutaminase (TGase) upregulation in astrocyte cultures (14 DIV). A 24 h exposure to glutamate caused a dose-dependent depletion of glutathione intracellular content and increased the ROS production in cell cultures. These effects were receptor-mediated, as demonstrated by inhibition with GYKI 52466. The pre-incubation with glutathione ethyl ester or cysteamine recovered oxidative status and was effective in significantly reducing glutamate-increased tissue TGase. These data suggest that tissue TGase upregulation may be part of a biochemical response to oxidative stress induced by a prolonged exposure of astrocyte cultures to glutamate.


Assuntos
Astrócitos/efeitos dos fármacos , Astrócitos/enzimologia , Proteínas de Ligação ao GTP/metabolismo , Ácido Glutâmico/farmacologia , Transglutaminases/metabolismo , Regulação para Cima , Animais , Animais Recém-Nascidos , Astrócitos/citologia , Astrócitos/fisiologia , Células Cultivadas , Relação Dose-Resposta a Droga , Glutationa/análogos & derivados , Glutationa/metabolismo , Oxirredução , Estresse Oxidativo , Proteína 2 Glutamina gama-Glutamiltransferase , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo
7.
Neurochem Int ; 5(6): 737-40, 1983.
Artigo em Inglês | MEDLINE | ID: mdl-20488004

RESUMO

RNA synthesis was studied in cerebral cortex, thalamus and brain stem of rat, on the 3rd, 8th, 30th and 75th day after cerebellectomy. An increased RNA synthesis was detected in thalamus at the 30th day and in cerebral cortex and brain stem at the 75th day after cerebellectomy. Our findings suggest that motor compensation following the cerebellectomy could be supported by a spatio-temporal organization of macromolecular synthesis in different brain regions.

8.
Brain Res ; 894(1): 1-11, 2001 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-11245809

RESUMO

We have examined the distribution of transforming growth factor-beta1 (TGF-beta1) and bone morphogenetic protein-6 (BMP-6) in the brain of rats subjected to a mild and reversible ischemic damage produced by a 20-min occlusion of both carotid arteries without occlusion of the vertebral arteries. We have selected this model to study how the expression of trophic factor of the TGF-beta superfamily changes in neurons that recover from a transient insult. Immunocytochemical analysis showed a loss of TGF-beta1 in neurons of all hippocampal subfields immediately after the ischemic period, followed by a recovery of immunoreactivity in CA1 and CA3 neurons after reperfusion. BMP-6 immunoreactivity was also lost in most hippocampal neurons, but immunostaining became particularly intense in the interstitial space after both ischemia and reperfusion. An interstitial localization of BMP-6 was also observed in the cerebral cortex, particularly after reperfusion. Mild ischemia also induced substantial changes in the expression of TGF-beta1 and BMP-6 within the cerebellar cortex. In control animals, these factors appeared to be localized in granule cells (TGF-beta1) and Purkinje cells (both), whereas the molecular layer was not immunopositive. Both TGF-beta1 and BMP-6 were highly expressed in the interstitial spaces of the cerebellar cortex either 20 min after ischemia or 20 min after reperfusion. Taken collectively, these results suggest that a mild and reversible ischemia stimulates the release of BMP-6 from neurons into the interstitial space. We speculate that BMP-6, besides functioning during brain development, may also regulate neuronal resistance to insults of the adult brain.


Assuntos
Proteínas Morfogenéticas Ósseas/metabolismo , Isquemia Encefálica/metabolismo , Cerebelo/metabolismo , Córtex Cerebral/metabolismo , Hipocampo/metabolismo , Neurônios/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Proteína Morfogenética Óssea 6 , Masculino , Células Piramidais/metabolismo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Fator de Crescimento Transformador beta1
9.
Brain Res ; 978(1-2): 24-30, 2003 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-12834894

RESUMO

Glutamate exposure of astroglial cells caused ligand-gated channel receptor activation, associated with excitotoxic cell response. We investigated the effects of 24 h glutamate exposure on transglutaminase in astrocytes primary cultures at 7, 14, and 21 days in vitro (DIV). Increases in enzyme activity were observed as a function of cell differentiation stage in glutamate-treated cultures. These effects were significantly reduced when GYKI 52466, an AMPA/KA receptors inhibitor, was added to the culture medium prior to incubation with glutamate. Microscopy observation on transglutaminase-mediated, fluorescent dansylcadaverine incorporation in living cells was consistent with these results. Western blotting analysis with monoclonal antibody showed that glutamate also up-regulated tissue transglutaminase expression, which reached the highest values in 14 DIV cultures. Confocal laser scanning microscopy analysis of immunostained astroglial cells showed a mainly cytoplasmic localisation of the enzyme both in control and treated cultures; nevertheless, counterstaining with the nuclear dye acridine orange demonstrated the presence of tissue transglutaminase also into the nucleus of glutamate-exposed and 21 DIV cells. The increases in enzyme expression and localisation in the nucleus of glutamate-treated astroglial cells may be part of biochemical alterations induced by excitotoxic stimulus.


Assuntos
Astrócitos/efeitos dos fármacos , Benzodiazepinas , Cadaverina/análogos & derivados , Fármacos Atuantes sobre Aminoácidos Excitatórios/farmacologia , Ácido Glutâmico/farmacologia , Transglutaminases/metabolismo , Animais , Animais Recém-Nascidos , Ansiolíticos/farmacologia , Astrócitos/metabolismo , Western Blotting/métodos , Cadaverina/metabolismo , Células Cultivadas , Relação Dose-Resposta a Droga , Interações Medicamentosas , Antagonistas de Aminoácidos Excitatórios/farmacologia , Glutamato-Amônia Ligase/análise , Imuno-Histoquímica/métodos , Microscopia Confocal/métodos , Ratos , Ratos Wistar , Fatores de Tempo , Transglutaminases/análise
10.
Int J Dev Neurosci ; 16(6): 519-26, 1998 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9881300

RESUMO

In the present study astrocytes reactivity during cerebral post-ischemic reperfusion was evaluated immunocytochemically by using antibodies to vimentin, glial fibrillary acidic protein (GFAP) and S-100 protein. At the 7th day of post-ischemic reperfusion few GFAP-positive cells were observed in the hippocampus and cerebellum, the number of GFAP-positive cells increased slightly after 20 days of reperfusion. This poor GFAP-positivity may be due to the inhibition of GFAP polymerization by S-100; in fact, S-100 immuno-reactivity was already evident from the 7th day. Vimentin immuno-staining was evident both at the 7th and 20th day of reperfusion in microglial cells and in oligodendrocytes, suggesting that these cells are involved in the recovery of neurons following brain injury.


Assuntos
Isquemia Encefálica/metabolismo , Proteína Glial Fibrilar Ácida/análise , Traumatismo por Reperfusão/metabolismo , Proteínas S100/análise , Vimentina/análise , Animais , Astrócitos/química , Química Encefálica/fisiologia , Cerebelo/irrigação sanguínea , Cerebelo/química , Cerebelo/citologia , Circulação Cerebrovascular/fisiologia , Hipocampo/irrigação sanguínea , Hipocampo/química , Hipocampo/citologia , Masculino , Microcirculação/fisiologia , Microglia/química , Oligodendroglia/química , Ratos , Ratos Wistar
11.
Int J Dev Neurosci ; 7(3): 233-41, 1989.
Artigo em Inglês | MEDLINE | ID: mdl-2756844

RESUMO

The survival of neural tissues depends in part on the balance between the formation of free radicals due to oxidative metabolism and the transformation of the free radicals to non-toxic compounds. Serial subculture of rat glial cells as described here resulted in a decrease of the specific activities of several antioxidant enzymes and a glial specific marker for astrocytes. Thus, there was an increased susceptibility to oxidative stress in cultures by the third passage. These subcultured glial cell cultures may represent a useful model for the study of free radical induced neural damage that may be relevant to CNS trauma and aging.


Assuntos
Astrócitos/enzimologia , Catalase/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Consumo de Oxigênio , Animais , Sobrevivência Celular , Células Cultivadas , Radicais Livres , Ratos
12.
Int J Dev Neurosci ; 9(4): 365-9, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1683098

RESUMO

Glutamate, aspartate, GABA, glycine and taurine levels have been measured in rat thalamus and in cerebral cortex at different time intervals (3rd, 7th, 15th, 30th day) after cerebellectomy. A decrease in glutamate, aspartate and GABA was detected at the 7th day after cerebellectomy in the thalamus and at the 15th day in the cerebral cortex; at the 30th day after cerebellectomy the levels of these amino acids in the thalamus and in the cerebral cortex were observed to have recovered to control values. No statistically significant difference in glycine and taurine levels in the thalamus and in the cerebral cortex after cerebellectomy could be seen. These results show that the functional recovery process after cerebellar injury is associated with a complex modification of amino acid levels in thalamus and in cerebral cortex.


Assuntos
Aminoácidos/metabolismo , Cerebelo/fisiologia , Córtex Cerebral/metabolismo , Neurotransmissores/metabolismo , Tálamo/metabolismo , Animais , Ácido Aspártico/metabolismo , Glutamatos/metabolismo , Ácido Glutâmico , Glicina/metabolismo , Masculino , Ratos , Ratos Endogâmicos , Valores de Referência , Fatores de Tempo , Ácido gama-Aminobutírico/metabolismo
13.
Int J Dev Neurosci ; 10(1): 75-80, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1609622

RESUMO

Although the role of oxidant-antioxidant metabolism in total ischemia and reperfusion in the central nervous system and cardiac myocardium have been well studied, less is known about the consequences of partial ischemic episodes. Here we show that reperfusion contributes to free radical formation as judged by conjugated diene formation. Also, antioxidants and Ca++ antagonists were able to reduce free radical formation. These results would suggest that free radical generation following ischemia and reperfusion may result from more than one injury process in cerebral cortex.


Assuntos
Antioxidantes/farmacologia , Isquemia Encefálica/metabolismo , Bloqueadores dos Canais de Cálcio/farmacologia , Córtex Cerebral/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Animais , Isquemia Encefálica/enzimologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/enzimologia , Radicais Livres/metabolismo , Glutationa/metabolismo , Lactatos/metabolismo , Masculino , Ratos , Ratos Endogâmicos , Reperfusão , Xantina Desidrogenase/metabolismo , Xantina Oxidase/metabolismo
14.
Exp Biol Med (Maywood) ; 228(5): 486-90, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12709574

RESUMO

Selective inhibitors of neuronal nitric oxide synthase (nNOS), which are devoid of any effect on the endothelial isoform (eNOS), may be required for the treatment of some neurological disorders. In our search for novel nNOS inhibitors, we recently described some 1-[(Aryloxy)ethyl]-1H-imidazoles as interesting molecules for their selectivity for nNOS against eNOS. This work reports a new series of 1-[(Aryloxy)alkyl]-1H-imidazoles in which a longer methylene chain is present between the imidazole and the phenol part of molecule. Some of these molecules were found to be more potent nNOS inhibitors than the parent ethylenic compounds, although this increase in potency resulted in a partial loss of selectivity. The most interesting compound was investigated to establish its mechanism of action and was found to interact with the tetrahydrobiopterin (BH(4)) binding site of nNOS, without interference with any other cofactors or substrate binding sites.


Assuntos
Biopterinas/análogos & derivados , Imidazóis/farmacologia , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase/metabolismo , Antioxidantes/metabolismo , Sítios de Ligação , Biopterinas/metabolismo , Imidazóis/química , Imidazóis/metabolismo , Estrutura Molecular , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase Tipo I , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
15.
Life Sci ; 33(6): 555-9, 1983 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-6136887

RESUMO

Transglutaminase may be an important intracellular regulator of protein function through its ability to catalyze the calcium-dependent covalent linkage of primary amines to glutamine residues in peptide linkage with the generation of ammonia. This study provides further evidence that a major alteration in tumor cells is the marked decline in the expression of transglutaminase activity. This may alter its known protein cross-linking activity and favor lack of differentiation and proliferation.


Assuntos
Aciltransferases/metabolismo , Sarcoma de Yoshida/enzimologia , Animais , Cinética , Masculino , Putrescina/metabolismo , Ratos , Ratos Endogâmicos , Transglutaminases
16.
Neurotoxicology ; 25(5): 877-84, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15288518

RESUMO

The present paper reports the effects of norepinephrine depletion in rats, after treatment with N-(2-chloroethyl)-N-ethyl 2-bromobenzylamine (DSP-4) neurotoxin, on partial cerebral ischemia and reperfusion. Histological observations made under experimental conditions of noradrenergic (NA)-depletion demonstrated that neuronal lesions were not exacerbated; in fact, in DSP-4-treated ischemic animals, a minor number of neurons appeared damaged. Our results suggest that neuronal recovery after post-ischemic reperfusion is not affected by NA-depletion. DSP-4 neurotoxin does not induce 5-hydroxy-triptamine (5-HT) depletion.


Assuntos
Lesões Encefálicas/patologia , Isquemia Encefálica/patologia , Norepinefrina/fisiologia , Traumatismo por Reperfusão/patologia , Animais , Benzilaminas/farmacologia , Química Encefálica/efeitos dos fármacos , Química Encefálica/fisiologia , Córtex Cerebral/patologia , Corantes , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/ultraestrutura , Imuno-Histoquímica , Ataque Isquêmico Transitório/patologia , Ácido Láctico/metabolismo , Masculino , Ratos , Ratos Wistar , Serotonina/metabolismo , Coloração pela Prata
17.
Life Sci ; 76(5): 545-58, 2004 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-15556167

RESUMO

Propolis, a natural product derived from plant resins collected by honeybees, has been used for thousands of years in traditional medicine all over the world. The composition of the propolis depends upon the vegetation of the area from where it was collected and on the bee species. In this study, we investigated the antioxidant activity of a propolis sample, provided by NATURANDES-CHILE, collected in a temperate region of central Chile. In addition, this natural compound was tested for its antiproliferative capacity on KB (human mouth epidermoid carcinoma cells), Caco-2 (colon adenocarcinoma cells) and DU-145 (androgen-insensitive prostate cancer cells) human tumor cell lines. Results showed that this Chilean propolis sample exhibits interesting biological properties, correlated with its chemical composition and expressed by its capacity to scavenge free radicals and to inhibit tumor cell growth.


Assuntos
Antioxidantes/farmacologia , Proliferação de Células/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , DNA de Cadeia Simples/efeitos dos fármacos , Sequestradores de Radicais Livres/farmacologia , Própole/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Chile , Meios de Cultura , Radicais Livres/metabolismo , Humanos , Peróxido de Hidrogênio/toxicidade , Fotólise
18.
Physiol Behav ; 53(5): 951-7, 1993 May.
Artigo em Inglês | MEDLINE | ID: mdl-8511212

RESUMO

In the present study using crossfostering among three inbred mouse strains (C57BL/6, DBA/2, and Balb/c) we compared the effects of lactation with milk of different compositions on the development of NK cells cytotoxic activity. The results show that the pups from C57BL/6 and DBA/2 mice exhibit a significant early increase of NK cells cytotoxic activity when fostered by Balb/c dams, in comparison to those fostered by natural mothers. The analysis of proteins, lactose, and lipids showed difference among the strains for all components. Strain effects for days of lactation were also observed. The naso-anal length and the body weight of young mice showed differences with the strain of fostering mothers. The results indicate that the characteristic of maternal milk composition interacts with the inbred genetic susceptibility of the pups to elicit the full expression of the level of NK activity.


Assuntos
Citotoxicidade Imunológica/imunologia , Imunidade Materno-Adquirida/imunologia , Células Matadoras Naturais/imunologia , Lactação/imunologia , Comportamento Materno , Meio Social , Animais , Animais Recém-Nascidos , Feminino , Camundongos , Camundongos Endogâmicos , Leite/imunologia , Necessidades Nutricionais , Gravidez , Especificidade da Espécie
19.
Food Chem Toxicol ; 40(1): 25-31, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11731033

RESUMO

Fumonisins are mycotoxins produced by several Fusarium species (Fusarium verticilloides and F. proliferatum) that infest corn and other cereals. Fumonisin B(1) (FB(1)), structurally resembling sphingoid bases, is an inhibitor of ceramide synthetase, a key enzyme involved in de novo sphingolipid biosynthesis and in the reacylation of free sphingoid bases derived from sphingolipid turnover. This inhibitory effect leads to accumulation of free sphinganine and sphingosine and subsequent induction of cell death. However, the downstream effectors activated by these sphingolipids in the cell death-signalling pathway are little known. The aim of this study was to evaluate, in FB(1)-exposed human fibroblasts, the involvement of oxygen free radicals and of some other biochemical pathways, caspase-3 activity, poly(ADP-ribose)polymerase (PARP) cleavage and DNA damage evaluated by comet assay. Our results indicate that FB(1) treatment (48, 72 h and 10, 50, 100 microM) does not affect cellular viability. Conversely, after 72 h of treatment, FB(1) (50 and 100 microM) induced DNA damage, an enhancement of caspase-3-activity and cleavage of PARP compared to controls. In addition, FB(1) increased the expression of HSP70 in a concentration and time-dependent manner. Our results indicate that DNA damage of apoptotic type in human fibroblasts is caused by exposure to FB(1) at high concentrations and for a prolonged time and that the genotoxic potential of FB(1) has probably been underestimated and should be reconsidered.


Assuntos
Ácidos Carboxílicos/toxicidade , Dano ao DNA/efeitos dos fármacos , Fibroblastos/química , Fumonisinas , Apoptose/efeitos dos fármacos , Ácidos Carboxílicos/administração & dosagem , Caspase 3 , Caspases/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Radicais Livres , Proteínas de Choque Térmico HSP70/análise , Humanos , Poli(ADP-Ribose) Polimerases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fatores de Tempo
20.
Drugs Exp Clin Res ; 20(5): 185-9, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-7875054

RESUMO

In the present study the authors investigated the effect of pretreatment with exogenous antioxidants such as deferoxamine (iron chelating drug), allopurinol (competitive inhibitor of xanthine oxidase) and vitamin E (scavenger of oxygen free radicals) on lipid peroxidation in rat cerebral cortex after post-ischaemic reperfusion, and on the survival rate. The effect of pretreatment with two calcium-antagonist drugs (diltiazem and verapamil) was also evaluated under the same experimental conditions. Pretreatment with exogenous antioxidants and with calcium-antagonist drugs significantly decreased cerebral conjugated diene levels (index of lipoperoxidation) with a concomitant increase in survival with respect to untreated ischaemic rats.


Assuntos
Antioxidantes/farmacologia , Isquemia Encefálica/tratamento farmacológico , Peroxidação de Lipídeos/efeitos dos fármacos , Reperfusão , Alopurinol/farmacologia , Alopurinol/uso terapêutico , Animais , Antioxidantes/uso terapêutico , Desferroxamina/farmacologia , Desferroxamina/uso terapêutico , Diltiazem/farmacologia , Diltiazem/uso terapêutico , Masculino , Ratos , Ratos Wistar , Traumatismo por Reperfusão/tratamento farmacológico , Verapamil/farmacologia , Verapamil/uso terapêutico , Vitamina E/farmacologia , Vitamina E/uso terapêutico
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