3,966 research outputs found
A sinfonia do sagrado em Castro Alves: (Deus, Eros e mãe em Os escravos)
No full textTese (doutorado) - Universidade Federal de Santa Catarina, Centro de Comunicação e Expressão. Programa de Pós-Graduação em Literatura.No presente trabalho realiza-se uma leitura intertextual entre a Bíblia e Os escravos, coletânea de poemas de teor abolicionista do poeta romântico Antônio Frederico de Castro Alves (1847-1871), objetivando demonstrar que os textos poéticos arquitetam-se na desconstrução e reconstrução dos textos bíblicos. A leitura dos poemas centra-se nos personagens: Deus, Eros e Mãe, os quais conformam uma trindade poética/sagrada. A pesquisa divide-se em três movimentos: Prelúdios do sagrado no Romantismo, Tríade melódica e À guisa de coda: trindade poética. No primeiro efetuam-se algumas aproximações ao conceito do sagrado e aos Romantismos francês e brasileiro. O seguinte corresponde à leitura das composições, através das linhas melódicas: A dualidade de Deus, A ambivalência de Eros e O duplo calvário da Mãe escrava. E no último movimento amalgamam-se as inter-relações entre a trindade cristã e poética e os dramas bíblico e poético
Inhibition of the rat breast cytosolic bioactivation of ethanol to acetaldehyde by some plant polyphenols and folic acid
No full textThere is a well-established association between alcohol consumption and breast cancer risk. About 4% of the breast cancers in developed countries are estimated to be attributable to drinking alcohol. The mechanism of tumor promotion by alcohol remains unknown. Recent studies from our laboratory and others showed the ability of mammary tissue to bioactivate ethanol to mutagenic/carcinogenic acetaldehyde and free radicals. Xanthine oxidoreductase (XOR) is an enzyme involved in those biotransformation processes. In the present study, we provide evidence of the ability of different natural polyphenols and offolic acid derivatives to inhibit the biotransformation of alcohol to acetaldehyde by rat breast cytosolic XOR. Folic acid and dihydrofolic acid, at concentrations of 10 μM, inhibited 100% and 84%, respectively, of the cytosolic acetaldehyde formation. Thirty-five polyphenols were tested in these initial experiments: ellagic acid, myricetin, quercetin, luteolin, and apigenin inhibited 79-95% at μM concentrations. The remaining polyphenols were either less potent or noninhibitory of acetaldehyde formation at similar concentrations in these screening tests. Results are relevant to the known preventive effects of folic acid against alcohol-induced breast cancer and to their potential preventive actions if added to foods or alcoholic beverages.Fil: Maciel, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); ArgentinaFil: Castro, Gerardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); ArgentinaFil: Castro, Jose Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentin
Rat ventral prostate xanthine oxidaseg-mediated metabolism of acetaldehyde to acetyl radical
No full textAlcohol drinking is known to lead to deleterious effects on prostate epithelial cells from humans and experimental animals. The understanding of the mechanisms underlying these effects is relevant to intraprostatic ethanol treatment of benign prostatic hyperplasia and to shed some light into the conflictive results linking alcohol consumption to prostate cancer. In previous studies, we provided evidence about the presence in the rat ventral prostate of cytosolic and microsomal metabolic pathways of ethanol to acetaldehyde and 1-hydroxyethyl radical and about the low levels of alcohol dehydrogenase and aldehyde dehydrogenase. Acetaldehyde accumulation in prostate tissue and oxidative stress promotion were also observed. In this study, we report that in the ventral prostate cytosolic fraction, xanthine oxidoreductase is able to metabolize acetaldehyde to acetyl radical. The identification of the acetyl was performed by GC-MS of the silylated acetyl-PBN adduct. Reference adduct was generated chemically. Formation of acetyl was also observed using pure xanthine oxidase. The generation of acetyl by the prostate cytosol was inhibited by allopurinol, oxypurinol, diphenyleneiodonium chloride, folate, and ellagic acid. Results suggest that metabolism of ethanol to acetaldehyde and to 1-hydroxyethyl and acetyl radicals could be involved in the deleterious effects of alcohol drinking on prostate epithelial cells.Fil: Castro, Gerardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); ArgentinaFil: Costantini, Martin Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); ArgentinaFil: Castro, Jose Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentin
Oxidation of ethanol to acetaldehyde and free radicals by rat testicular microsomes
No full textA large number of epidemiological studies evidencing that excessive alcohol consumption is associated with impaired testosterone production and testicular atrophy are available in the literature. One hypothesis to explain the deleterious action of alcohol involves the in situ biotransformation to acetaldehyde, but it strongly suggests the need to learn more about the enzymatic processes governing alcohol metabolism to acetaldehyde in different cellular fractions since limited information is available in the literature. In this article we report studies on the metabolic conversion of alcohol to acetaldehyde and to 1-hydroxyethyl radicals in rat testicular microsomal fractions. The oxidation of ethanol to acetaldehyde in rat testes microsomal fraction was mostly of enzymatic nature and strongly dependent on the presence of NADPH and oxygen. Several compounds were able to significantly decrease the production of acetaldehyde: SKF 525A; diethyldithiocarbamate; esculetin; gossypol; curcumin; quercetin; dapsone; and diphenyleneiodonium. Microsomal preparations in the presence of NADPH were also able to produce both hydroxyl and 1-hydroxyethyl free radicals. Their generation was modulated by the presence of diphenyleneiodonium, gossypol, and deferoxamine. Results show that rat microsomal fractions are able to metabolize alcohol to deleterious chemicals, such as acetaldehyde and free radicals, that may be involved in ethanol toxic effects. Enzymes involved could include CYP2E1, P450 reductase, and other enzymes having lipoxygenase- /peroxidase-like behavior.Fil: Quintans, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); ArgentinaFil: Castro, Gerardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); ArgentinaFil: Castro, Jose Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentin
Alcohol drinking and mammary cancer: Pathogenesis and potential dietary preventive alternatives
No full textAlcohol consumption is associated with an increased risk of breast cancer, increasing linearly even with a moderate consumption and irrespectively of the type of alcoholic beverage. It shows no dependency from other risk factors like menopausal status, oral contraceptives, hormone replacement therapy, or genetic history of breast cancer. The precise mechanism for the effect of drinking alcohol in mammary cancer promotion is still far from being established. Studies by our laboratory suggest that acetaldehyde produced in situ and accumulated in mammary tissue because of poor detoxicating mechanisms might play a role in mutational and promotional events. Additional studies indicated the production of reactive oxygen species accompanied of decreases in vitamin E and GSH contents and of glutathione transferase activity. The resulting oxidative stress might also play a relevant role in several stages of the carcinogenic process. There are reported in literature studies showing that plasmatic levels of estrogens significantly increased after alcohol drinking and that the breast cancer risk is higher in receptor ER-positive individuals. Estrogens are known that they may produce breast cancer by actions on ER and also as chemical carcinogens, as a consequence of their oxidation leading to reactive metabolites. In this review we introduce our working hypothesis integrating the acetaldehyde and the oxidative stress effects with those involving increased estrogen levels. We also analyze potential preventive actions that might be accessible. There remains the fact that alcohol drinking is just one of the avoidable causes of breast cancer and that, at present, the suggested acceptable dose for prevention of this risk is of one drink per day.Fil: Castro, Gerardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; ArgentinaFil: Castro, Jose Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; Argentina. Universidad Nacional de San Martín. Instituto de Investigación e Ingeniería Ambiental; Argentin
Alcohol consumption and reproductive toxicity: The role of in situ metabolism of ethanol in target organs
No full textEpidemiological studies conducted in different countries showed that alcohol abuse in the youth and the adolescent is a problem of growing interest and relevance. Consequently, it can be envisaged that the number of adult drinkers is going to increase in the years to come. The detrimental effect of alcohol consumption on the health of young people is particularly serious when one considers that, with respect to reproductive health, this is the age range more relevant in both sexes. In women, reproductive health is not a minor issue, considering the alarming increase in drinking at an age directly related to the fertility window. It is important to note that due to differences in the metabolism of ethanol, women, compared with men, is facing an increased risk of negative consequences associated with the consumption of large amounts of alcohol. Harmful consequences of alcohol abuse have been reported in women such as a significant risk of infertility and an increased risk for endometriosis. Other studies concluded that the probability of a successful pregnancy decreased with the increase in the consumption of alcohol. For men, a large number of epidemiological studies evidenced that excessive alcohol consumption is associated with impaired testosterone production and testicular atrophy. Reproductive disorders caused by drinking should certainly involve alterations in critical hormonal factors controlling reproductive functions but also related to the direct toxic action of ethanol and its metabolites in the organs that constitute the reproductive systems of both sexes.Fil: Castro, Jose Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; Argentina. Ministerio de Defensa. Instituto de Investigaciones Científicas y Técnicas para la Defensa; ArgentinaFil: Castro, Gerardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigación y Desarrollo Estratégico para la Defensa. Ministerio de Defensa. Unidad de Investigación y Desarrollo Estratégico para la Defensa; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentina. Ministerio de Defensa. Instituto de Investigaciones Científicas y Técnicas para la Defensa; Argentin
Rat liver microsomal and nuclear activation of methanol to hydroxymethyl free radicals
No full textRecent studies from other laboratories reported that during methanol intoxication lipid peroxidation and protein oxidation in liver occurred. Further, they detected free radicals-PBN adducts in bile and urine of methanol poisoned rats. In this work, we report the presence in liver microsomes and nuclei of NADPH dependent processes of hydroxymethyl (HMet) radical formation. The detection of HMet radicals was performed by GC/MS of the trimethylsilyl derivatives of the PBN (N-tert-butyl-a-phenylnitrone)-radical adducts. The formation of HMet radicals was observed only under nitrogen, in these in vitro conditions. Formation of formaldehyde from methanol was observed in aerobic incubation mixtures containing either microsomes or nuclei but also under nitrogen using microsomes. The latter process was not inhibited by diphenyleneiodonium while the anaerobic microsomal one producing HMet was strongly inhibited by it. This shows that they are independent processes. Results suggest that both, liver nuclei and microsomes are able to generate free radicals during NADPH-mediated methanol biotransformation.Fil: Castro, Gerardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); ArgentinaFil: Costantini, Martin Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); ArgentinaFil: Delgado De Layño, Aurora, M. A.. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); ArgentinaFil: Castro, Jose Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentin
Rat ventral prostate microsomal biotransformation of ethanol to acetaldehyde and 1-hydroxyethyl radicals: Its potential contribution to prostate tumor promotion
No full textRat ventral prostate microsomal fraction was able to biotransform ethanol to acetaldehyde and 1-hydroxyethyl radicals (1HEt) in the presence of NADPH and oxygen. The enzymatic processes involved were not inhibited by desferrioxamine, CO, SKF 525A, 4-methylpyrazole, or polyclonal antibody against P450 reductase but they were significantly inhibited by diethyldithiocarbamate, 2-mercapto-1-methylimidazol, thiobenzamide, or diphenyleneiodonium chloride. Results would suggest the partial participation in these ethanol bioactivation processes of flavin containing monooxygenase (FMO) and/or other flavin dependent oxidases/ peroxidases and of a non-iron metal-containing enzymes. Acetaldehyde and free radicals production by prostate microsomal fraction might potentially contribute to tumor promotion in heavy alcohol drinkers.Fil: Castro, Gerardo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); ArgentinaFil: Delgado De Layño, Aurora, M. A.. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); ArgentinaFil: Costantini, Martin Hernan. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); ArgentinaFil: Castro, Jose Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentin
Genotoxicidad en leucocitos por la quimioprofilaxis de sangre con Violeta de Genciana y su prevención con antioxidantes
No full textEl violeta de genciana (GV) se usa como aditivo en la sangre para eliminar el Trypanosoma cruzi en la quimioprofilaxis de la infección por enfermedad de Chagas vía transfusión sanguínea, cuando no es posible un control previo de laboratorio o bajo situaciones de emergencia. En estos estudios se encontraron efectos genotóxicos del GV empleando el ensayo Cometa, cuando el se lo agrega a la sangre bajo las condiciones empleadas para esterilizarla para transfusión. El efecto genotóxico fue aún más intenso si la sangre se mantiene con GV por 48 horas. Los resultados obtenidos con el ensayo Cometa sugieren la formación de bases hidroxiladas de ADN como resultado de un ataque de especies reactivas de oxígeno y apoyan la genotoxicidad del GV y su potencial carcinogénico ya informado previamente. Los efectos genotóxicos observados en el ensayo Cometa fueron parcialmente prevenidos por administración previa a la rata donante de la sangre de antioxidantes que ya tienen uso clínico seguro, como α-tocoferol; ácido lipoico o N-acetilcisteína. El ácido lipoico fue capaz también de reaccionar in vitro con GV. Los resultados sugieren un uso potencial de estos antioxidantes para prevenir los efectos secundarios no deseados del GV para el individuo recipiente de la sangre.Fil: Diaz Gomez, Maria Isabel. Universidad Nacional de San Martin. Instituto de Investigación e Ingeniería Ambiental; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigacion y Desarrollo Estrategicos para la Defensa; Argentina;Fil: Castro, Jose Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad de Investigacion y Desarrollo Estrategicos para la Defensa; Argentina; Universidad Nacional de San Martin. Instituto de Investigación e Ingeniería Ambiental; Argentina
Nifurtimox biotransformation to reactive metabolites or nitrite in liver subcellular fractions and model systems
No full textLiver microsomal (mic); nuclei (N) and mitochondria (mit) anaerobically nitroreduce Nifurtimox (Nfx) in the presence of NADPH generating system. Simultaneous formation of small amounts of nitrite was observed in microsomes and nuclei but not in mitochondria. The microsomal nitroreductase activity was enhanced by the presence of flavine-adenine-dinucleotide disodium salt (FAD), was not inhibited by CO and was significantly inhibited by diphenyleneiodonium (DPI). In the microsomal NADPH-dependent fraction nitrite formation was null in the presence of FAD, DPI and under air and was partially inhibited by pure CO. Pure human cytochrome P450 reductase in the presence of NADPH significantly nitroreduced Nfx and produced small amounts of nitrite. The nitroreductive process was significantly enhanced by FAD but the nitrite formation became null. FAD itself was able to chemically nitroreduce Nfx without production of nitrite. NADPH generating system enhanced the FAD nitroreductive effect and led to small production of nitrite. Formation of reactive metabolites and nitric oxide during Nfx metabolism might contribute to its toxicity.Fil: Montalto, Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); ArgentinaFil: Diaz, Edith Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); ArgentinaFil: Castro, Jose Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. GP. CITEFA - Centro de Investigaciones Toxicológicas (I); Argentin
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