924 resultados para hepatocellular damage


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beta-Glucans (BGs) are polysaccharides that are found in the cell walls of organisms such as bacteria, fungi, and some cereals. The objective of the present study was to investigate the genotoxic and antigenotoxic effects of BG extracted from the mushroom Agaricus brasiliensis (=Agaricus blazei Murrill ss. Heinemann). The mutagenic activity of BG was tested in single-cell gel electrophoresis assays with human peripheral lymphocytes. In addition, the protective effects against the cooked food mutagen 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and (+/-)-anti-B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE), which is the main metabolite of B[a]P, and against ROS (H2O2)-induced DNA damage, were studied. The results showed that the compound itself was devoid of mutagenic activity, and that a significant dose-dependent protective effect against damage induced by hydrogen peroxide and Trp-P-2 occurred in the dose range 20-80 mu g/ml. To investigate the prevention of Trp-P-2-induced DNA damage, a binding assay was carried out to determine whether BG inactivates the amine via direct binding. Since no such interactions were observed, it is likely that BG interacts with enzymes involved in the metabolism of the amine.

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A large number of functional foods, including those that contain P-glucan, have been shown to prevent the development of cancer and other chronic diseases. The aim of the present study was to elucidate its mechanism of action, as well as to understand its effects as an antigenotoxic, anticlastogenic agent, and to determine its capacity to preserve cell viability. The investigation was carried out in the CHO-k1 and CHO-xrs5 cell lines. The cytokinesis-blocked micronucleus assay indicated that the different doses of beta-glucan examined (5, 10, 20 and 40 mu g/ml) did not show clastogenic effects. In the CHO-k1 cell line, a chemopreventive effect could be observed in all the protocols tested: pre-treatment (% reduction of 35.0-57.3), simultaneous treatment (simple - 5 reduction of 19.7-55.6 and with pre-incubation - of 42.7-56.4) and post-treatment (% reduction of 17.9-37.6). This finding indicates mechanisms of action involving desmutagenesis and bio-antimutagenesis, albeit the latter having a lesser role. However, in the repair-deficient CHO-xrs5 cells, beta-glucan did not show a protective effect with post-treatment (% reduction of 2.96), thus supporting the involvement of bioantimutagenesis. The comet assay in CHO-k1 cells demonstrated that beta-glucan has neither a genotoxic nor an antigenotoxic effect. Cell viability tests indicated that beta-glucan preserves cell viability in both cell lines, preventing apoptotic events. These findings suggest that beta-glucan, when present in foods, could provide them with nutraceutical characteristics and act as a dietary supplement, or that P-glucan could be used in new drug development. (c) 2006 Elsevier Ltd. All rights reserved.

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Although neotropical savannas and grasslands, collectively referred to as cerrado, are rich in seed-eating species of rodents, little is known about seed predation and its determinants in this habitat. In this study, we investigated seed predation and damage to fruits of the widespread shrub Solarium lycocarpurn. In addition, the influence of two possible determinants (distance from the parental plant and total crop size) on the feeding behaviour of Oryzorrys scotti (Rodentia, Sigmodontinae) was also examined. O. scotti were captured more frequently close to the shrubs or on shrub crops, indicating that these rodents were attracted to the shrubs and that seed predation was probably distance-dependent. Moreover, the proportion of damaged fruit on the plant decreased as the total crop size increased; consequently, more productive plants were attacked proportionally less by rodents. This pattern of fruit damage may reflect predator satiation caused by the consumption of a large amount of pulp. Alternatively, secondary metabolites in S. lycocarpum fruits may reduce the pulp consumption per feeding event, thereby limiting the number of fruits damaged. (c) 2006 Elsevier Masson SAS. All rights reserved.

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Animal venoms have been valuable sources for development of new drugs and important tools to understand cellular functioning in health and disease. The venom of Polybia paulista, a neotropical social wasp belonging to the subfamily Polistinae, has been sampled by headspace solid phase microextraction and analyzed by gas chromatography-mass spectrometry. Recent study has shown that mastoparan, a major basic peptide isolated from the venom, reproduces the myotoxic effect of the whole venom. In this study, Polybia-MPII mastoparan was synthesized and studies using transmission electron microscopy were carried out in mice tibial anterior muscle to identify the subcellular targets of its myotoxic action. The effects were followed at 3 and 24 h, 3, 7, and 21 days after mastoparan (0.25 mu g/mu L) intramuscular injection. The peptide caused disruption of the sarcolemma and collapse of myofibril arrangement in myofibers. As a consequence, fibers presented heteromorphic amorphous masses of agglutinated myofilaments very often intermingled with denuded sarcoplasmic areas sometimes only surrounded by a persistent basal lamina. To a lesser extent, a number of fibers apparently did not present sarcolemma rupture but instead appeared with multiple small vacuoles. The results showed that sarcolemma, sarcoplasmic reticulum (SR), and mitochondria were the main targets for mastoparan. In addition, a number of fibers showed apoptotic-like nuclei suggesting that the peptide causes death both by necrosis and apoptosis. This study presents a hitherto unexplored view of the effects of mastoparan in skeletal muscle and contributes to discuss how the known pharmacology of the peptide is reflected in the sarcolemma, SR, mitochondria, and nucleus of muscle fibers, apparently its subcellular targets.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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This work presents an analysis of the wavelet-Galerkin method for one-dimensional elastoplastic-damage problems. Time-stepping algorithm for non-linear dynamics is presented. Numerical treatment of the constitutive models is developed by the use of return-mapping algorithm. For spacial discretization we can use wavelet-Galerkin method instead of standard finite element method. This approach allows to locate singularities. The discrete formulation developed can be applied to the simulation of one-dimensional problems for elastic-plastic-damage models. (C) 2007 Elsevier B.V. All rights reserved.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Studies of DNA damage in gastric epithelial cells of Helicobacter pylori (H. pylori)-infected patients are conflicting, possibly due to different methods used for scoring DNA damage by Comet assay. Therefore, we compared the sensitivity of visual microscopic analysis (arbitrary units-scores and comets%) and image analysis system (tail moment), in the gastric epithelial cells from the antrum and corpus of 122 H. pylori-infected and 32 non-infected patients. The feasibility of cryopreserved peripheral blood lymphocytes and whole-blood cells for DNA damage biomonitoring was also investigated. In the antrum, the levels of DNA damage were significantly higher in H. pylori-infected patients with gastritis than in non-infected patients with normal mucosa, when evaluated by image analysis system, arbitrary units and comets%. In the corpus, the comets% was not sufficiently sensitive to detect the difference between H. pylori-infected patients with gastritis and non-infected patients with normal mucosa. The image analysis system was sensitive enough to detect differences between non-infected patients and H. pylori-infected patients with mild gastritis and between infected patients with moderate and severe gastritis, in both antrum, and corpus, while arbitrary units and comets% were unable to detect these differences. In cryopreserved peripheral blood lymphocytes, the levels of DNA damage (tail moment) were significantly higher in H. pylori-infected patients with moderate and severe gastritis than in non-infected patients. Overall, our results indicate that the image analysis system is more sensitive and adequate to measure the levels of DNA damage in gastric epithelial cells than the other methods assayed. (c) 2005 Elsevier B.V. All rights reserved.