Abstract This study investigated the effects of the flavonoids 5-hydroxy-7,4′-dimethoxyflavone, casticin, and penduletin, isolated from Croton betulaster Müll Arg., Euphorbiaceae, a plant utilized in popular medicine in Brazil, on the growth and viability of the human glioblastoma cell line GL-15. We observed that 5-hydroxy-7,4′-dimethoxyflavone and casticin were not toxic to GL-15 cells after 24 h of exposure. However, casticin and penduletin inhibited the metabolic activity of glioblastoma cells significantly at a concentration of 10 µM (p ≤ 0.05). Flavonoids casticin and penduletin also induced a significant and dose-dependent growth inhibition beginning at 24 h of exposure, and the most potent flavonoid was penduletin. It was also observed that penduletin and casticin induced an enlargement of the cell body and a reduction of cellular processes, accompanied by changes in the pattern of expression of the cytoskeletal protein vimentin. Signs of apoptosis, such as the externalization of membrane phosphatidyl serine residues, nuclear condensation, and fragmentation, were also detected in cells treated with 50–100 µM flavonoids. Our results indicate that flavonoids extracted from C. betulaster present antitumoral activity to glioblastoma cells, with penduletin proving to be the most potent of the tested flavonoids. Our results also suggest that these molecules may be promising supplementary drugs for glioblastoma treatment.

OBJETIVO: O objetivo deste trabalho foi estudar a influência da dieta ovo-lácteo-vegetariana e do exercício físico extenuante sobre as atividades das enzimas catalase e superóxido dismutase em dez indivíduos masculinos, jovens e saudáveis. MÉTODOS: O controle alimentar aplicou-se por quatro meses. Antes disso, foram recolhidas amostras de sangue em estado basal e cinco minutos após o exercício físico extenuante efetuado em esteira rolante. O mesmo procedimento foi aplicado após o controle alimentar. RESULTADOS: Os resultados mostraram que a dieta ovo-lácteo-vegetariana, em condições de repouso, reduziu de forma significativa a atividade da enzima catalase em 18,98% (p<0,05) e aumentou, também de forma significativa, a atividade da enzima superóxido dismutase em 77,84% (p<0,001). Depois do exercício físico extenuante, a dieta ovo-lácteo-vegetariana reduziu a atividade da enzima catalase de forma significativa em 26,11% (p<0,05) e não alterou a atividade da enzima superóxido dismutase. CONCLUSÃO: Os resultados indicam que tanto as atividades da catalase como da superóxido dismutase são sensíveis a uma dieta ovo-lácteo-vegetariana adequada.

OBJECTIVE: This study aimed to study the influence of an ovolactovegetarian diet and strenuous physical exercise on the activity of the enzymes catalase and superoxide dismutase in 10 young, healthy men whose diet was controlled for four months. METHODS: Blood samples were collected at baseline and after the four-month period, before strenuous exercise and after 5 minutes of strenuous exercise on a treadmill. RESULTS: The results showed that the ovolactovegetarian diet reduced the activity of the enzyme catalase by 18.98% (p<0.05) and increased the activity of the enzyme superoxide dismutase by 77.84% (p<0.001) before strenuous exercise. After strenuous exercise, the ovolactovegetarian diet reduced the activity of the enzyme catalase by 26.11% (p<0.05) and did not affect the activity of the enzyme superoxide dismutase. CONCLUSION: The results indicate that a healthy ovolactovegetarian diet impacts the activity of both enzymes.

Foi isolado das folhas de Nanuza plicata um novo biflavonóide, chamado 3',8"-biisocampferideo (1), juntamente com os conhecidos compostos amentoflavona (2), ácido patagônico(3),(4aR,5S,6R,8aR)-5-[2-(2,5-dihidro-5-metóxi-2-oxofuran-3-il)etil]-3,4,4a,5,6,7,8, 8a-octahidro-5,6,8a-trimetilnaftaleno-1-ácido carboxílico (4), cafeoilquinato de metila (5), ácido 3,5-di-cafeoilquínico (6) e luteolina (7). Os compostos 3, 4, 5 e 6 são relatados pela primeira vez em Velloziaceae. As estruturas dos compostos foram elucidadas com base em métodos espectroscópicos, especialmente RMN e EM. A citotoxicidade de 3',8"-biisocampferideo foi estudada em células de glioblastoma humano (GL-15). A concentração efetiva, que produziu morte em 50% das células após 72 h foi 36,5 µmol L-1. Alterações na morfologia celular, incluindo retração e degradação de citoplasma, foram observadas quando as células foram tratadas com concentrações a partir de 20 µmol L-1 de 3',8"-biisocampferideo por 72h.

A novel biflavonoid, named 3',8"-biisokaempferide (1), along with the known compounds amentoflavone (2), patagonic acid (3), (4aR,5S,6R,8aR)-5-[2-(2,5-Dihydro-5-methoxy-2-oxofuran-3-yl)ethyl]-3,4,4a,5,6,7,8,8a-octahydro-5,6,8a-trimethylnaphthalene-1-carboxylic acid (4), 5-caffeoylquinic acid methyl ester (5), 3,5-di-caffeoylquinic acid (6) and luteolin (7), were isolated of the leaves from Nanuza plicata. The compounds 3, 4, 5 and 6 are reported for the first time in Velloziaceae. The structures of the compounds were elucidated on the basis of spectroscopic methods, especially NMR and MS analyses. The cytotoxicity of 3',8"-biisokaempferide was studied in cultures of human glioblastoma GL-15 cells. The effective concentration, which killed 50 % of cells after 72 h was 36.5 µmol L-1. Changes in cellular morphology, including retraction and degradation of cytoplasm, were observed when cells were treated with concentrations from 20 µmol L-1 of 3',8"-biisokaempferide for 72 h.

OBJECTIVE: The aim of this study was to observe the protective role of a diet based on the culinary culture of Bahia State against an oxidative stress induced by strenuous exercise in 17 young and healthy individuals. METHODS: Meat, palm oil, fruit juices, roots, manioc flour and cereals are the main constituents of this diet. Dietary control had a span of four months. Before the dietetic regime started blood samples were collected from each individual both at rest and also five minutes after a bout of strenuous exercise. Samples were collected again both at rest and after the bout of strenuous exercise at the end of the dietary intervention. RESULTS: The oxidative status was assessed measuring catalase and superoxide dismutase activities in erythrocytes, and lipid peroxidation in membranes of these cells. These parameters were not affected by the diet when at rest. The strenuous exercise did not interfere with superoxide dismutase activities and lipid peroxidation before and after the dietary intervention. However, strenuous exercise induced an increase in catalase activities before and after the dietary regime (19.49 and 11.74% respectively). Moreover, this effect was significantly (p<0,05) less pronounced (26.11%) as a result of the diet. CONCLUSION: These data suggest that antioxidants present in the Bahia State diet can down-regulate the increase in catalase activity induced by strenuous exercise.

OBJETIVO: El objetivo de este trabajo fue estudiar el efecto de la dieta afro-bahiana sobre el estrés oxidativo inducido por el ejercicio físico extenuante en 17 individuos jóvenes y saludables. MÉTODOS: La dieta afro-bahiana se compone principalmente de carne roja, aceite de palma, zumo de frutas, raíces, harina de mandioca y cereales. El control alimenticio se extendió por 4 meses. Antes del control alimenticio, se retiraron muestras de sangre en estado basal y cinco minutos después de un ejercicio físico extenuante en tapiz rodante. El mismo procedimiento fue seguido después del control alimenticio. Para analizar el efecto de la dieta y del ejercicio físico extenuante se compararon los indicadores antioxidantes, catalasa y superóxido dismutasa y el estrés oxidativo por la peroxidación lipídica, determinada por el análisis del malonaldeído en eritrocitos. RESULTADOS: Los resultados muestran que la dieta, en condición de reposo, no influenció significativamente el estatus antioxidante de las enzimas catalasa y superóxido dismutasa ni la concentración de análisis del malonaldeído. Se observa, no obstante, que después de un ejercicio físico extenuante, la actividad de la catalasa, tanto con dieta libre como después de la dieta afro-bahiana, aumentó de forma significativa (p<0,05) en 19,49 y 11,74%, respectivamente. La actividad del superóxido dismutasa y concentración de análisis del malonaldeído no se alteraron. La actividad de la catalasa después del ejercicio físico extenuante fue significativamente menor (p<0,05) después de la dieta afro-baiana (26,11%). CONCLUSIONES: Estos datos sugieren la presencia de antioxidantes en la dieta afro-bahiana capaces de interferir en el aumento de la actividad de la catalasa inducida por el ejercicio físico extenuante.

OBJETIVO: Testar a hipótese do catecol inibir a respiração basal associada ao FADH2 em frações mitocondriais hepáticas de rato. Além disso, estudou-se também a capacidade do catecol de induzir peroxidação de biomoléculas nas frações nucleares. MÉTODOS: Os homogeneizados de fígado de ratos foram incubados com catecol a 1 mM em pH fisiológico. Depois disso, as frações mitocondriais foram isoladas por centrifugação diferencial. O consumo basal de oxigênio foi medido com um eletrodo do tipo Clark após injeção de succinato a 10 mM. Frações nucleares foram incubadas com catecol por 17 horas à temperatura ambiente e a peroxidação de biomoléculas foi investigada pela reação com o ácido tiobarbitúrico e mensurada espectrofotometricamente. RESULTADOS: O catecol induziu uma inibição parcial da respiração basal mitocondrial associada ao FADH2 de forma dependente do tempo, contudo essa substância não induziu peroxidação direta das biomoléculas presentes nas frações nucleares hepáticas. CONCLUSÃO: O catecol produz inibição da respiração basal associada ao FADH2 em mitocôndrias isoladas de fígado, o que pode levar à toxicidade, produção de espécies reativas e morte celular.

PURPOSE: The aim of this work was to investigate the hypothesis that catechol inhibits FADH2-linked basal respiration in mitochondria isolated from rat liver homogenates. Moreover, catechol ability to induce peroxidation of biomolecules in liver nuclear fractions was also studied. METHODS: Rat liver homogenates were incubated with 1mM 1,2-dihydroxybenzene (catechol) at pH 7.4 for up to 30 minutes. After that, mitochondrial fractions were isolated by differential centrifugation. Basal oxygen uptake was measured using a Clark-type electrode after the addition of 10 mM sodium succinate. Nuclear fractions were incubated in the presence of 1 mM catechol for 17 hours at room temperature and the peroxidation of biomolecules was investigated by the reaction with thiobarbituric acid, which was determined spectrophotometrically at 535 nm. RESULTS: Catechol induced a time-dependent partial inhibition of FADH2-linked basal mitochondrial respiration, however this substance was unable to induce a direct peroxidation of biomolecules in hepatic nuclear fractions. CONCLUSION: Catechol produced an inhibition of basal respiration associated to FADH2 in isolated liver mitochondria that could lead to cytotoxicity, ROS generation and cell death.

Sabe-se que a exposição de trabalhadores ao benzeno na indústria petrolífera é uma causa de câncer do sistema linfo-hematopoiético. Pouco se sabe, contudo, a respeito da toxicidade do benzeno no sistema nervoso central. O benzeno penetra facilmente no cérebro, onde é metabolizado a catecol. Como o catecol se auto-oxida em tampão fosfato no pH fisiológico, supôs-se que esse composto poderia ser tóxico para células gliais por gerar espécies reativas do oxigênio e quinonas. Nesse trabalho estudou-se a citotoxicidade do catecol para células de glioblastoma humano. O catecol foi tóxico após 72 horas e essa toxicidade relacionou-se com a formação de quinonas. O catecol a 230mM matou metade das células em cultura. A toxicidade do catecol e a produção de quinonas foram inibidas por 100U de superóxido dismutase. Esses dados sugerem que a toxicidade induzida pelo catecol deve-se à produção extracelular de superóxido e quinonas reativas.

It is known that the exposure to benzene in the petroleum industry causes lympho-haematopoietic cancer among workers. However, there is little data concerning the toxicity of benzene to the central nervous system. Benzene easily penetrates the brain where it is metabolized to catechol. Since catechol autoxidizes in physiological phosphate buffer, we hypothesized that it could be toxic towards glial cells due to the generation of reactive oxygen species and quinones. In this work we studied the cytotoxic properties of catechol towards human glioblastoma cells. We found that catechol was toxic towards these cells after 72 hours and this toxicity was related to the formation of quinones. Catechol at 230µM killed 50% of cells. The catechol-induced cytotoxicity was prevented by the addition of 100U superoxide dismutase, which also inhibited the formation of quinones. These data suggest that catechol induces cytotoxicity via the extracellular generation of superoxide and quinones.