960 resultados para CYTOTOXIC PYRIDONE ALKALOIDS


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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Trans-dehydrocrotonin, the major diterpene isolated from the bark of Croton cajucara, has good antiulcerogenic activity which, however, is accompanied by toxic effects. on the basis of these results, a semi-synthetic crotonin, named 4SRC, was prepared to determine whether this substance has similar antiulcerogenic activity with lower or no toxicity. The natural crotonin was also isolated from the bark of C. cajucara but was not used due to the small amount obtained. The cytotoxic effect of semi-synthetic crotonin, expressed as cell viability, was assessed in (a) lung fibroblast cell line (V79) derived from Chinese hamsters, a system commonly used for cytotoxicity studies, and (b) rat hepatocytes isolated from male Wistar rats. After treatment, cell viability was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide reduction (MTT reduction), total acid content and neutral red uptake assays. To evaluate V79 cell viability, different concentrations of semi-synthetic crotonin were incubated with the cells. To evaluate the antiulcerogenic effects of semi-synthetic crotonin (50, 100 and 200 mg/kg), we used the models of gastric ulcer induced by ethanol/HCl, stress, indomethacin/bethanechol, and ethanol in male Swiss mice and male Wistar rats. The substance had an IC50 = 500 muM in the neutral red uptake and MTT reduction tests and an IC50 = 200 muM in the nucleic acid content test. With regard to hepatocyte viability after treatment with semi-synthetic crotonin at different concentrations, semi-synthetic crotonin had an IC50 = 10-500 muM in the nucleic acid content and MTT reduction tests and an IC50 = 120 muM in the neutral red uptake test. In another experiment, V79 cells were incubated with the metabolites produced by hepatocytes treated with different concentrations of semi-synthetic crotonin. After a 4-h incubation, semi-synthetic crotonin had an IC50 = 500 muM in the MTT reduction and neutral red uptake tests and an IC50 = 370 muM in nucleic acid content test. The substance had significant antiulcerogenic activity in all models studied, suggesting the presence of a possible antisecretory effect combined with a cytoprotective effect. For this reason, the effect of semi-synthetic crotonin was also evaluated on biochemical parameters of gastric juice and gastric wall mucus, both obtained from pylorus-ligated mice. No significant differences were observed in these parameters between semi-synthetic crotonin-treated and control animals. The results obtained with semi-synthetic crotonin are promising, with a significant preventive effect against gastric ulcer induced by different agents. Our data also show that semi-synthetic crotonin was less toxic than dehydrocrotonin and that the cytotoxic effects decreases with the time that isolated hepatocytes were in culture. (C) 2003 Elsevier B.V. B.V. All rights reserved.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Objectives Propolis is a honeybee product used extensively in traditional medicine for its antioxidant, anti-inflammatory, immunomodulatory and anticancer effects. Propolis exhibits a broad spectrum of biological activities because it is a complex mixture of natural substances. In this review, the antitumour effects of propolis extracts and its constituents (e. g. flavonoids, terpenes and caffeic acid phenethyl ester) are discussed.Key findings The effect of propolis on experimental carcinogenesis is discussed, as well as its possible mechanisms of action against tumours, involving apoptosis, cell cycle arrest and interference on metabolic pathways. Propolis seems to be efficient against different tumour cells both in vitro and in vivo, which suggests its potential in the development of new anticancer drugs.Summary Propolis extracts may be important economically and would allow a relatively inexpensive cancer treatment. Preclinical investigations are needed to further elucidate the benefits of propolis and its antitumour properties.

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

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Textile dyes are discarded into the aquatic ecosystem via industrial effluents and potentially expose humans and local biota to adverse effects. The commercial dye CI Disperse Blue 291 which contains the aminoazobenzene 2-[(2-bromo-4,6-dinitrophenyl)azo]-5(diethylamino)-4-methoxyacetanilide (CAS registry no. 56548-64-2), was tested for genotoxicity and cytotoxicity in the human hepatoma cell line HepG2, using the comet assay, micronucleus (MN) test and a cell viability test. Five different concentrations of the test compound were examined: 200 mu g/ml, 400 mu g/ml, 600 mu g/ml, 800 mu g/ml and 1000 mu g/ml. An increase in comet tail length and in the frequency of MN was detected with exposure of cells to concentrations of the commercial dye from 400 pg/ml. Furthermore, the dye was found to decrease cell viability. The results of this study demonstrate for the first time the genotoxic and mutagenic effects of the dye CI Disperse Blue 291 in mammalian cells, thus stressing the need to develop non-mutagenic dyes and to invest in improving the treatment of effluents. These measures will help to prevent harmful effects that these compounds can have on humans and aquatic organisms that come in contact with them. (C) 2007 Elsevier Ltd. All rights reserved.

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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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The ovary of the Rhipicephalus sanguineus dog tick female is structurally formed by oocytes in five different stages of development (from I to V) and attached to the gonad by the pedicel. The present study evaluated possible toxic effects of the acaricide fipronil (Frontline (R)) on ovaries of semi-engorged ticks. Sixty partially fed females of R. sanguineus tick were distributed into four groups of 15 specimens each: I - non-treated; II, III and IV - treated with 1, 5 and 10 ppm of fipronil, respectively. The acaricide induced structural changes in the oocytes of individuals of the different treated groups ranging from the presence of a few small vacuoles to cellular death. In conclusion, germinative cells of semi-engorged R. sanguineus tick female are affected by different concentrations of fipronil leading to the reduction of tick fertility. (c) 2008 Elsevier Ltd. All rights reserved.

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Rutin is a flavonoid with antioxidant, vasodilatory, anti-inflammatory and immune-stimulating activities. To study the toxicity of rutin and its protective effect, this work investigated the cytotoxic, apoptosis-inducing, genotoxic and protective effects of rutin in HTC cells. In the MTT assay, the highest concentration tested (810 mu M) showed cytotoxicity after 72 h of treatment, where cell viability and cell proliferation was diminished. None of the concentrations of rutin tested induced apoptosis after 24 h treatment. The highest concentration of rutin after 24 h treatment induced DNA damage, shown in the comet assay, but did have a genotoxic effect in the micronucleus test. Rutin was tested against the pro-carcinogenic agent benzo(a)pyrene, at concentrations of 90, 270 and 810 mu M, and was found to reduce induced DNA damage significantly. This protective effect of rutin against a pro-carcinogen, suggests an important biological activity for this compound, which can contribute to human health through the diet. (C) 2010 Elsevier GmbH. All rights reserved.

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Quinolizidine alkaloids (QAs) are secondary compounds found in seeds of many species of plants, possibly protecting them against pathogens and seed predators. QAs were isolated from Ormosia arborea seeds and bioassayed against red-rumped agoutis (Dasyprocta leporina, Rodentia: Caviomorpha) to verify if they inhibit seed predation and food hoarding (seed dispersal). Three treatments were used: (1) seeds of O. arborea, (2) palatable seeds of Mimusops coriacea (Sapotaceae) treated with MeOH, and (3) seeds of M. coriacea treated with QAs dissolved in MeOH in similar concentration to that present in O. arborea. Palatable seeds were significantly more preyed upon than seeds treated with QAs and Ormosia seeds, but QAs did not influence hoarding behavior. QAs in O. arborea may have a strong effect in avoiding seed predation by rodents, without reducing dispersal.

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