Atividades antiúlcera e antioxidante de Syzygium jambos(L. ) Alston / Antiulcer and antioxidant activities of Syzygium jambos(L. ) Alston

O jambeiro (Syzygium jambos (L.) Alston) constitui uma das diversas espécies frutíferas e medicinais pertencentes à família Myrtaceae. O extrato hidroetanólico a 70 ´POR CENTO´ liofilizado de folhas de S. jambos apresentou atividade dose-dependente em modelo de úlcera gástrica induzida por etanol acidificado, sendo que a dose de 400 mg/kg reduziu significativamente a Área Total de Lesão (81,64%) e a Área Relativa de Lesão (65,11%), em comparação ao grupo controle. Nesta dose, o extrato apresentou-se mais eficaz que o fármaco empregado como referência (Iansoprazol 30 mg/kg). No modelo de indução de úlcera gástrica por ácido acético, o extrato (400 mg/kg) não apresentou resultados significativos na cura das lesões. A atividade antioxidante do mesmo extrato e de quatro frações foi avaliada através da medida da capacidade seqüestrante de radicais 1, 1-difenil-2-picrilidrazila. O extrato hidroetanólico a 70% liofilizado apresentou CE `IND.50´ de 5,36 ± 0,06 µg/mL, valor comparável ao do Trolox (CE `IND.50´ = 4,98 ± 0,04 µg/mL), substância antioxidante de referência...

Propriedades Redox de canais de potássio mitocondriais ATP-sensíveis em cérebro e seu efeito neuroprotetor em excitotoxicidade / Redox properties of brain mitochondrial ATP-sensitive potassium channels and neuroprotective effects in excitotoxicity

Muitos estudos demonstram que a abertura de canais de ´KPOT.+` mitocondriais sensíveis à ATP (mito´K ind.ATP`) previnem contra danos promovidos por isquemia/reperfusao em coração. Em geral, esta proteçao envolve mudanças no estado redox mitocondrial. Em cérebro, sabe-se que agonistas farmacológicos de mito´K ind.ATP` também protegem em modelo de isquemia/reperfusão. Entretanto, os mecanismos envolvidos na prevenção de danos em cérebro ainda não estão claros. 0 objetivo principal deste trabalho é compreender os efeitos de canais de K+ mitocondriais ATP-sensíveis em tecido cerebral e os mecanismos pelos quais a sua ativação pode proteger contra danos promovidos por excitotoxicidade, uma das principais consequências de um evento isquêmico em cerebro. Neste contexto, demonstramos a proteção pelo mito´K ind.ATP` em modelo de excitotoxicidade induzida pela ativação direta de receptores NMDA, utilizando cultura de células granulosas de cerebelo. Paralelamente a essa proteção, verificamos que a ativação de mito´K ind.ATP` reduz a geração de espécies reativas de oxigênio (ROS)...

Preimplantation embryotoxicity after mouse embryo exposition to reactive oxygen species

Exposure of either gametes or embryos to conditions and/or factors that generate oxidative stress has been associated with impaired early embryogenesis. The effects of reactive oxygen species (ROS) on mouse preimplantation development, depending of the ROS-concentration and time of exposition, were studied. Two-cell embryos were incubated with 5, 10, 25 and 50 microM of hydrogen peroxide (H2O2) for 30 and 60 minutes of exposition and allowed to develop for 72 h to study the quality of Development. The incubation with 50 microM H2O2 for 30 or 60 minutes, strongly inhibited the 2-cell embryo development as compared to the control (p < 0.001). Twenty-five microM H2O2 produced inhibition of blastocyst formation (p < 0.001) and 10 microM H2O2 significantly decreased the percentages of expanded and hatchedblastocysts, which resulted morphologically altered (p < 0.05 and p < 0.01, respectively). The higher H2O2 concentrations were able to elicit necrotic morphology in the 2-cell arrested embryos, while 10 microM H2O2 induced moderate damage with the arrested embryos partially fragmented. In conclusion, important causes for defective preimplantation development and for early embryo losses may be due to oxidative stress because early mouse embryos exposed to ROS for short times arrested at the first cellular cycle (2-cell) and/or impaired embryo differentiation and morphogenesis, being these effects ROS-concentration-dependent.

Relationship between Pulmonary Surfactant Protein and Lipid Peroxidation in Lung Injury due to Paraquat Intoxication in Rats

BACKGROUND: Pulmonary damage resulting from lipid peroxidation is a principal effect of paraquat intoxication. The host-defense functions of surfactant are known to be mediated by the surfactant proteins A and D (SP-A and SP-D, respectively). The primary objective of this study was to evaluate the variations over time in levels of surfactant protein and lipid peroxidation (LPO) in lung tissue following free-radical-induced injury. METHODS: 42 adult, male, Sprague-Dawley rats were administered intraperitoneal injections of paraquat (35 mg/kg body weight). SP-A and SP-D levels were determined via Western blot. LPO in the left lung homogenate was measured via analyses of the levels of thiobarbituric acid-reactive substances. RESULTS: LPO levels peaked at 6 hours, with no associated histological changes. SP-D levels increased until hour 12 and declined until hour 48; SP-D levels subsequently began to increase again, peaking at hour 72. SP-A levels peaked at hour 6, declining thereafter. CONCLUSIONS: We suggest that in the early phase of paraquat injury, SP-D levels reflect alveolar damage and that de novo synthesis of SP-D takes 72 hours. Levels of SP-A, on the other hand, reflect abnormalities in the surfactant system in the late stage of paraquat intoxication. Surfactant proteins may play a role in protecting the lungs from reactive oxygen injury. A time-dependent variation has been observed in the levels of surfactant proteins A and D following paraquat injury, and it has been suggested that these proteins play a role in the protection of lung tissue against ROS-induced injuries.

Oxidants, antioxidants and carcinogenesis.

Reactive oxygen metabolites (ROMs), such as superoxide anions (O2*-) hydrogen peroxide (H2O2), and hydroxyl radical (*OH), malondialdehyde (MDA) and nitric oxide (NO) are directly or indirectly involved in multistage process of carcinogenesis. They are mainly involved in DNA damage leading sometimes to mutations in tumour suppressor genes. They also act as initiator and/or promotor in carcinogenesis. Some of them are mutagenic in mammalian systems. O2*-, H2O2 and *OH are reported to be involved in higher frequencies of sister chromatid exchanges (SCEs) and chromosome breaks and gaps (CBGs). MDA, a bi-product of lipid peroxidation (LPO), is said to be involved in DNA adduct formations, which are believed to be responsible for carcinogenesis. NO, on the other hand, plays a duel role in cancer. At high concentration it kills tumour cells, but at low concentration it promotes tumour growth and metastasis. It causes DNA single and double strand breaks. The metabolites of NO such as peroxynitrite (OONO-) is a potent mutagen that can induce transversion mutations. NO can stimulate O2*-/H2O2/*OH-induced LPO. These deleterious actions of oxidants can be countered by antioxidant defence system in humans. There are first line defense antioxidants such as superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT). SOD converts O2*- to H2O2, which is further converted to H2O with the help of GPx and CAT. SOD inhibits *OH production. SOD also act as antipoliferative agent, anticarcinogens, and inhibitor at initiation and promotion/transformation stage in carcinogenesis. GPx is another antioxidative enzyme which catalyses to convert H2O2, to H2O. The most potent enzyme is CAT. GPx and CAT are important in the inactivation of many environmental mutagens. CAT is also found to reduce the SCE levels and chromosomal aberrations. Antioxidative vitamins such as vitamin A, E, and C have a number of biological activities such as immune stimulation, inhibition of nitrosamine formation and an alteration of metabolic activations of carcinogens. They can prevent genetic changes by inhibiting DNA damage induced by the ROMs. Therefore, these antioxidants may be helpful in the treatment of human cancer. However, detailed studies are required to draw a definite conclusion.

Specific limb abnormalities induced by hydrogen peroxide in tadpoles of Indian jumping frog, Polypedates maculatus.

Hydrogen peroxide (H2O2), one of the reactive oxygen intermediates (ROI) and a potential inducer of nuclear transcription factors induces consistent type of abnormal limb development (truncated with bent skeletal elements) in the tadpoles of Indian jumping frog, Polypedates maculatus.

The effects of ascorbic acid on free radical injury in cultured retinal pigment epithelial cells

This study was conducted to investigate the effect of ascorbic acid on oxidative injury of cultured porcine retinal pigment epithelial (RPE) cells induced by t-butylhydroperoxide. The porcine RPE cells were cultured in Dulbecco's modified Eagle's medium and the culture medium was replaced with one containing 0.01 mM to 5 mM ascorbic acid and/or 0.2 mM t-butylhydroperoxide. After 2 hours incubation, the test medium was replaced with the control medium. The number of cells was counted with a Coulter counter after a 2-day incubation period. The medium was pretreated with 900 U/ml and the previous procedure was repeated to eliminate the toxic effects of hydrogen peroxide induced by ascorbic acid. Not only t-butylhydroperoxide (p 0.05). The cytotoxicity of t-butylhydroperoxide decreased when 1 mM and 5 mM of ascorbic acid was added to the culture media with catalase pretreatment (p = 0.0277). These results indicate that ascorbic acid was toxic to RPE cells in our culture model but this cytotoxicity was not detected in the presence of catalase. With catalase pretreatment, ascorbic acid in relatively high concentration provided protection against oxidative injury of t-butylhydroperoxide.