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Braz. j. med. biol. res ; 44(11): 1156-1163, Nov. 2011. ilus
Artigo em Inglês | LILACS | ID: lil-604283


We evaluated the potential neuroprotective effect of 1-100 µM of four organoselenium compounds: diphenyl diselenide, 3’3-ditri-fluoromethyldiphenyl diselenide, p-methoxy-diphenyl diselenide, and p-chloro-diphenyl diselenide, against methylmercury-induced mitochondrial dysfunction and oxidative stress in mitochondrial-enriched fractions from adult Swiss mouse brain. Methylmercury (10-100 µM) significantly decreased mitochondrial activity, assessed by MTT reduction assay, in a dose-dependent manner, which occurred in parallel with increased glutathione oxidation, hydroperoxide formation (xylenol orange assay) and lipid peroxidation end-products (thiobarbituric acid reactive substances, TBARS). The co-incubation with diphenyl diselenide (100 µM) completely prevented the disruption of mitochondrial activity as well as the increase in TBARS levels caused by methylmercury. The compound 3’3-ditrifluoromethyldiphenyl diselenide provided a partial but significant protection against methylmercury-induced mitochondrial dysfunction (45.4 ± 5.8 percent inhibition of the methylmercury effect). Diphenyl diselenide showed a higher thiol peroxidase activity compared to the other three compounds. Catalase blocked methylmercury-induced TBARS, pointing to hydrogen peroxide as a vector during methylmercury toxicity in this model. This result also suggests that thiol peroxidase activity of organoselenium compounds accounts for their protective actions against methylmercury-induced oxidative stress. Our results show that diphenyl diselenide and potentially other organoselenium compounds may represent important molecules in the search for an improved therapy against the deleterious effects of methylmercury as well as other mercury compounds.

Animais , Masculino , Camundongos , Encéfalo/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Intoxicação do Sistema Nervoso por Mercúrio/prevenção & controle , Compostos de Metilmercúrio/toxicidade , Mitocôndrias/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Compostos Organosselênicos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Análise de Variância , Derivados de Benzeno/farmacologia , Fracionamento Celular , Modelos Animais , Fármacos Neuroprotetores/classificação , Compostos Organosselênicos/química
Biol. Res ; 42(2): 163-173, 2009. ilus, tab, graf
Artigo em Inglês | LILACS | ID: lil-524886


Some selenium compounds offer important health benefits when administered at supranutritional doses, such as improvement of the immune system and of male fertility, and the prevention of some types of cancer. The traditional selenium indexes do not account for the metabolic status of this element among replete individuals. As a consequence, there is a need for new indexes that distinguish between repletion statuses of selenium. The aim of this work was to indentify some plasmatic proteins that respond to supranutritional doses of selenium, which could be proposed as new protein markers of selenium intake. The effect on rats of dietary supplementation with either selenomethylselenocysteine (SMSeC) or sodium-selenate on some blood plasma proteins was investigated. Two experimental groups consisting of six rats each were fed a basic diet supplemented with either SMSeC or sodium-selenate at 1.9 mg-Se / g-diet for ten weeks. The control group was fed a diet that contained the recommended selenium dose (0.15 mg-Se / g-diet). The changes in the abundance of a group of plasmatic proteins were quantified and analysed statistically. Haptoglobin, apolipoprotein E and transthyretin increased their abundance after diet supplementation with either form of selenium. HNF6 was responsive only to SMSeC, whereas fibrinogen responded only to sodium-selenate. We postulate that the protein patterns observed in this work could be proposed as new molecular biology-based markers of selenium intake.

Animais , Masculino , Ratos , Proteínas Sanguíneas/efeitos dos fármacos , Cisteína/análogos & derivados , Suplementos Nutricionais , Compostos Organosselênicos/administração & dosagem , Compostos de Selênio/administração & dosagem , Selênio/sangue , Proteínas Sanguíneas/análise , Cisteína/administração & dosagem , Eletroforese em Gel Bidimensional , Espectrometria de Massas , Ratos Wistar
Braz. j. med. biol. res ; 40(10): 1287-1304, Oct. 2007. ilus, tab
Artigo em Inglês | LILACS | ID: lil-461366


The pharmacology of synthetic organoselenium compounds indicates that they can be used as antioxidants, enzyme inhibitors, neuroprotectors, anti-tumor and anti-infectious agents, and immunomodulators. In this review, we focus on the effects of diphenyl diselenide (DPDS) in various biological model organisms. DPDS possesses antioxidant activity, confirmed in several in vitro and in vivo systems, and thus has a protective effect against hepatic, renal and gastric injuries, in addition to its neuroprotective activity. The activity of the compound on the central nervous system has been studied since DPDS has lipophilic characteristics, increasing adenylyl cyclase activity and inhibiting glutamate and MK-801 binding to rat synaptic membranes. Systemic administration facilitates the formation of long-term object recognition memory in mice and has a protective effect against brain ischemia and on reserpine-induced orofacial dyskinesia in rats. On the other hand, DPDS may be toxic, mainly because of its interaction with thiol groups. In the yeast Saccharomyces cerevisiae, the molecule acts as a pro-oxidant by depleting free glutathione. Administration to mice during cadmium intoxication has the opposite effect, reducing oxidative stress in various tissues. DPDS is a potent inhibitor of d-aminolevulinate dehydratase and chronic exposure to high doses of this compound has central effects on mouse brain, as well as liver and renal toxicity. Genotoxicity of this compound has been assessed in bacteria, haploid and diploid yeast and in a tumor cell line.

Animais , Camundongos , Ratos , Antioxidantes/farmacologia , Derivados de Benzeno/farmacologia , Compostos Organosselênicos/farmacologia , Sintase do Porfobilinogênio/antagonistas & inibidores , Saccharomyces cerevisiae/efeitos dos fármacos , Derivados de Benzeno/toxicidade , Modelos Biológicos , Testes de Mutagenicidade , Compostos Organosselênicos/toxicidade
Braz. j. med. biol. res ; 35(6): 623-631, June 2002. ilus
Artigo em Inglês | LILACS | ID: lil-309507


The interaction of the product of H2O2 and (PhSe)2 with delta-aminolevulinate dehydratase (delta-ALA-D) from mammals and plants was investigated. (PhSe)2 inhibited rat hepatic delta-ALA-D with an IC50 of 10 æM but not the enzyme from cucumber leaves. The reaction of (PhSe)2 with H2O2 for 1 h increased the inhibitory potency of the original compound and the IC50 for animal delta-ALA-D inhibition was decreased from 10 to 2 æM. delta-ALA-D from cucumber leaves was also inhibited by the products of reaction of (PhSe)2 with H2O2 with an IC50 of 4 æM. The major product of reaction of (PhSe)2 with H2O2 was identified as seleninic acid and produced an intermediate with a lambdamax at 265 nm after reaction with t-BuSH. These results suggest that the interaction of (PhSe)2 with mammal delta-ALA-D requires the presence of cysteinyl residues in close proximity. Two cysteine residues in spatial proximity have been recently described for the mammalian enzyme. Analysis of the primary structure of plant delta-ALA-D did not reveal an analogous site. In contrast to (PhSe)2, seleninic acid, as a result of the higher electrophilic nature of its selenium atom, may react with additional cysteinyl residue(s) in mammalian delta-ALA-D and also with cysteinyl residues from cucumber leaves located at a site distinct from that found at the B and A sites in mammals. Although the interaction of organochalcogens with H2O2 may have some antioxidant properties, the formation of seleninic acid as a product of this reaction may increase the toxicity of organic chalcogens such as (PhSe)2

Animais , Bovinos , Ratos , Cucumis sativus , Peróxido de Hidrogênio , Fígado , Compostos Organosselênicos , Sintase do Porfobilinogênio , Análise de Variância