Evaluation of DNA damage and lipoperoxidation of propofol in patients undergoing elective surgery

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Lipoperoxidation and cyclooxygenase enzyme inhibitory piperidine alkaloids from Cassia spectabilis green fruits

Phytochernical work in the search for bioactive metabolites from the methanolic extract of Senna spectabilis green fruits led to the isolation of a new piperidine alkaloid, (+)-3-O-feruloylcassine (1), in addition to the known (-)-spectaline (2) and (-)-3-O-acetylspectaline (3). The isolates were submitted to in vitro evaluation of lipoperoxidation (LPO) and cyclooxygenase enzymes (COX-1 and -2) inhibitory properties and showed moderate antioxidant activities (40-70%) at 100 ppm when compared to commercial standards BHT and vitamin E and moderate inhibition of COX-1 (ca. 40%) and marginal inhibition of COX-2 enzymes (< 10%) at 100 ppm when compared to nonsteroidal anti-inflammatory drugs (NSAIDs) aspirin, rofecoxib, and celecoxib, respectively.

Lipoperoxidation and cyclooxygenases 1 and 2 inhibitory compounds from Iryanthera juruensis

Plants from Iryanthera genus have been traditionally used as food supplements by South American Indians. The MeOH extract of leaves of Iryanthera juruensis, one of the plants endemic to the Amazon region and consumed in Brazil, and the hexane extract from its seeds inhibited lipid peroxidation (LPO) and cyclooxygenase (COX-1 and -2)) enzymes in in vitro assays. Further analyses of these extracts yielded 5-deoxyflavones (1-5) from the leaf extract and sargachromenol (6), sargaquinoic acid (7), a novel juruenolic acid (8), omega-arylalkanoic acids (9a-c), and the lignan guaiacin (10) from the seed extract. Compounds 3-5 inhibited LPO by 86%, 77%, and 88% at 10 ppm, respectively, and compounds 6 and 9a-c showed inhibition at 76% and 78% at 100 ppm, respectively. However, compounds 7 and 8 were inactive and lignan 10 exhibited LPO inhibitory activity by 99% at 100 ppm compared to commercial antioxidants butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and vitamin E. The flavones 1-5 also inhibited COX-1 and -2 enzymes by 50-65% at 100 ppm. Compound 6 showed high but nonselective inhibition of COX-1 and COX-2 enzymes, when compared to aspirin and Celebrex, a nonsteroidal anti-inflammatory drug (NSAID). Compounds 7 and 10 inhibited COX-1 by 60% and 65% and COX-2 by 37% and 18%, respectively, whereas compounds 8 and 9a-c showed little or no activity against these enzymes.

Evaluation of DNA damage and lipoperoxidation of propofol in patients undergoing elective surgery

Inhaled anaesthetics have been studied regarding their genotoxic and mutagenic potential in vivo. Propofol differs from volatile anaesthetics because it does not show mutagenic effects and it has been reported to be an antioxidant. However, there are no studies with propofol and genotoxicity in vivo. The study aimed to evaluate the hypothesis that propofol is not genotoxic and it inhibits lipid peroxidation [malondialdehyde (MDA)] in patients undergoing propofol anaesthesia. ASA physical status I patients scheduled for elective surgery, lasting at least 90 min, were enrolled in this study. Initially, the estimated plasma concentration of propofol was targeted at 4 microg ml(-1) and then maintained at 2-4 microg ml(-1) until the end of surgery. Haemodynamic data were determined at baseline (before premedication) and in conjunction with target-controlled infusion of propofol: after tracheal intubation, 30, 60 and 90 min after anaesthesia induction and at the end of the surgery. Venous blood samples were collected at baseline, after tracheal intubation, at the end of the surgery and on the postoperative first day for evaluating DNA damage in white blood cells (WBCs), by comet assay, and MDA levels. Haemodynamic data did not differ among times. No statistically significant differences were observed for the levels of DNA damage in WBCs, nor in plasma MDA, among the four times. Propofol does not induce DNA damage in WBCs and does not alter MDA in plasma of patients.

Trypanocidal action of eupomatenoid-5 is related to mitochondrion dysfunction and oxidative damage in Trypanosoma cruzi

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Papel da lipoperoxidação na intensificação da remodelação causada pelo betacaroteno após o infarto

FUNDAMENTO: Os mecanismos envolvidos na maior remodelação causada pelo betacaroteno após o infarto são desconhecidos. OBJETIVO: Analisar o papel da lipoperoxidação na remodelação ventricular após o infarto do miocárdio, em ratos suplementados com betacaroteno. MÉTODOS: Ratos foram infartados e distribuídos em dois grupos: C (controle) e BC (500mg/kg/dieta). Após seis meses, foram realizados ecocardiograma e avaliação bioquímica. Utilizamos o teste t, com significância de 5%. RESULTADOS: Os animais do grupo BC apresentaram maiores médias das áreas diastólicas (C = 1,57 ± 0,4 mm²/g, BC = 2,09 ± 0,3 mm²/g; p < 0,001) e sistólicas (C = 1,05 ± 0,3 mm²/g, BC = 1,61 ± 0,3 mm²/g; p < 0,001) do VE, ajustadas ao peso corporal do rato. A função sistólica do VE, avaliada pela fração de variação de área, foi menor nos animais suplementados com betacaroteno (C = 31,9 ± 9,3 %, BC = 23,6 ± 5,1 %; p = 0,006). Os animais suplementados com betacaroteno apresentaram valores maiores da relação E/A (C = 2,7 ± 2,5, BC = 5,1 ± 2,8; p = 0,036). Não foram encontradas diferenças entre os grupos em relação aos níveis cardíacos de GSH (C = 21 ± 8 nmol/mg de proteína, BC = 37 ±15 nmol/mg de proteína; p = 0,086), GSSG (C = 0,4 (0,3-0,5) nmol/g de proteína, BC = 0,8 (0,4-1,0; p = 0,19) de proteína; p = 0,246) e lipoperóxidos (C = 0,4 ± 0,2 nmol/mg de tecido, BC = 0,2 ± 0,1 nmol/mg de tecido; p = 0,086). CONCLUSÃO: A maior remodelação em animais infartados e suplementados com betacaroteno não depende da lipoperoxidação.

Treatment with Azadirachta indica in diabetic pregnant rats: Negative effects on maternal outcome

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

Malondialdeído e troponina I cardíaca em equinos da raça Puro Sangue Árabe submetidos ao exercício e à suplementação com vitamina E

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

Diet compounds, glycemic index and obesity-related cardiac effects

Background: Diet compounds may influence obesity-related cardiac oxidative stress and metabolic sifting. Carbohydrate-rich diet may be disadvantageous from fat-rich diet to cardiac tissue and glycemic index rather than lipid profile may predict the obesity-related cardiac effects.Materials and methods: Male Wistar rats were divided into three groups (n=8/group): (C) receiving standard chow (3.0 kcal/g); (CRD) receiving carbohydrate-rich diet (4.0 kcal/g), and (FRD) receiving fat-rich diet (4.0 kcal/g). Rats were sacrificed after the oral glucose tolerance test (OGTT) at 60 days of dietary treatments. Lipid profile and oxidative stress parameters were determined in serum. Myocardial samples were used to determine oxidative stress, metabolic enzymes, glycogen and triacylglycerol.Results: FRD rats showed higher final body weight and body mass index than CRD and C. Serum cholesterol and low-density lipoprotein were higher in FRD than in CRD, while triacylglycerol and oxidized low-density lipoprotein cholesterol were higher in CRD than in FRD. CRD rats had the highest myocardial lipid hydroperoxide and diminished superoxide dismutase and catalase activities. Myocardial glycogen was lower and triacylglycerol was higher in CRD than in C and FRD rats. Although FRD rats had depressed myocardial-reducing power, no significant changes were observed in myocardial energy metabolism. Myocardial beta-hydroxyacyl coenzyme-A dehydrogenase and citrate synthase, as well as the enhanced lactate debydrogenase/citrate synthase ratio indicated that fatty acid degradation was decreased in CRD rats. Glycemic index was positively correlated with obesity-related cardiac effects.Conclusions: Isoenergetic carbohydrate-rich and fat-rich diets induced different degree of obesity and differently affected lipid profile. Carbohydrate-rich diet was deleterious relative to fat-rich diet in the heart enhancing lipoperoxidation and shifting the metabolic pathway for energy production. Glycemic index rather than dyslipidemic profile may predict the obesity effects on cardiac tissue. (C) 2007 Elsevier B.V. All rights reserved.

Oxidative stress biomarkers and aggressive behavior in fish exposed to aquatic cadmium contamination

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Evaluation of the antiulcerogenic and analgesic activities of Cordia verbenacea DC. (Boraginaceae)

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

Butyl hydroxytoluene (BHT)-induced oxidative stress: Effects on serum lipids and cardiac energy metabolism in rats

Recent lines of evidences indicate that several pathological conditions, as cardiovascular diseases, are associated with oxidative stress. In order to validate a butylated hydroxytoluene (BHT)-induced experimental model of oxidative stress in the cardiac tissue and serum lipids, 12 Wistar rats were divided into two groups, a control group and the BHT group, Which received BHT i.p. twice a week (1500 mg/kg body Weight) during 30 days. BHT group presented lower body weight gain and heart weight. BHT induced toxic effects on serum through increased triacylglycerols (TG), VLDL and LDL-cholesterol concentrations. The heart of BHT animals showed alteration of antioxidant defenses and increased concentrations of lipid hydroperoxides, indicating elevated lipoperoxidation. TG concentrations and lactate dehydrogenase activities were elevated in the cardiac Muscle of BHT animals. Thus, long-term administration of BHT is capable to induce oxidative and metabolic alterations similarly to some pathological disorders, constituting an efficient experimental model to health scientific research. (c) 2005 Elsevier GrnbH. All rights reserved.

Avaliação de dois modelos experimentais de isquemia e reperfusão cerebral em ratos com oclusão temporária carotídea associada ou não à oclusão vertebral

OBJETIVO: Avaliar a reprodutibilidade de dois modelos experimentais de isquemia e reperfusão cerebral. MÉTODOS: 60 ratos foram distribuídos, aleatoriamente, em três grupos experimentais, com 20 animais cada: I - pinçamento temporário de artéria carótida esquerda; II - cauterização prévia das artérias vertebrais e pinçamento temporário da artéria carótida esquerda; simulado - sem isquemia nem reperfusão. Todos os animais tiveram oclusão definitiva de artéria carótida direita e os três grupos foram subdivididos em dois períodos de reperfusão: A - 60 minutos e B - 120 minutos. Os parâmetros verificados foram: medidas de pressão arterial média sistêmica e fluxo sangüíneo carotídeo; medida de malondialdeído cerebral através do teste TBARS e avaliação histológica do hemisfério cerebral submetido à isquemia e reperfusão. Foi feito também um estudo complementar com angiografia cerebral em 5 animais adicionais. RESULTADOS: Não houve diferenças significativas nas dosagens de malondialdeído cerebral e na freqüência e gravidade das alterações histológicas cerebrais entre os três grupos. Nos grupos GI e GII, a PAM foi significantemente maior no período de isquemia. O fluxo sangüíneo entre os períodos pré e pós-pinçamento aumentou nos grupos IA e IIB, diminuiu no grupo IB e no grupo IIA manteve-se inalterado. As angiografias do estudo complementar mostraram aporte sangüíneo para cérebro através de circulação colateral. CONCLUSÃO: Os modelos de isquemia e reperfusão estudados não demonstraram alterações consistentes de marcadores de lesão cerebral, seja quanto à produção de lipoperóxidos ou de lesões histológicas.

Diets rich in saturated and polyunsaturated fatty acids: Metabolic shifting and cardiac health

OBJECTIVE: the aim of this study was to determine the effects of diets rich in saturated and polyunsaturated fatty acids on metabolic pathways and the relation of metabolic shifting to oxidative stress in cardiac tissue.METHODS: Male Wistar rats (age, 60 d; n = 10) were fed with a control low-fat diet, a diet rich in saturated fatty acids (SFAs), or a diet rich in polyunsaturated fatty acids (PUFAs). After 5 wk of treatment, sera were used for protein and lipid determinations. Protein, glycogen, triacylglycerol, lactate dehydrogenase, citrate synthase, beta-hydroxyacyl coenzyme-A dehydrogenase, catalase, glutathione peroxidase, superoxide dismutase, lipoperoxide, and lipid hydroperoxide were measured in cardiac tissue.RESULTS: the SFA group had higher triacylglycerol, cholesterol, low-density lipoprotein cholesterol, and atherogenic index (ratio of cholesterol to high-density lipoprotein) than did the PUFA and control groups. The PUFA group had low serum cholesterol, triacylglycerol, and low-density lipoprotein cholesterol as compared with the SFA group. SFA increased myocardial lipid hydroperoxide and diminished glutathione peroxidase. Despite the beneficial effects on serum lipids, the PUFA diet led to the highest levels of myocardial lipoperoxide and lipid hydroperoxide and diminished superoxide dismutase and catalase activities. The PUFA effects were related to increased feed efficiency, increased susceptibility to lipoperoxidation, and metabolic shifting in cardiac tissue. PUFA elevated triacylglycerol levels and decreased myocardial glycogen concentrations. The ratios of lactate dehydrogenase to citrate synthase and beta-hydroxyacyl coenzyme-A dehydrogenase to citrate synthase were increased, indicating myocardial reduction of tricarboxylic acid cycle.CONCLUSIONS: PUFAs have been recommended as a therapeutic measure in preventive medicine to lower serum cholesterol, but PUFAs increased oxidative stress in the heart by providing cardiac susceptibility to lipoperoxidation and shifting the metabolic pathway for energy production. The control diet, which was much lower in calories and fat, produced better overall clinical outcomes, better fat profiles, and less oxidative stress than did the diets rich in fatty acids.

Lipoperoxidação, perda de viabilidade celular e diminuição da liberação de IL-8 de neutrófilos humanos na presença de corpos cetônicos

Type-1 diabetes patients suffer from frequent episodes of acidosis caused by an increased fatty acid metabolism and consequently increased plasma level of acetoacetate (AcAc) and β-hydroxybutyrate (β-HOB). This article describes a study of the effects of pathological concentrations of AcAc and β-HOB on lipoperoxidation, cell viability and the release of the CXCL8 (IL-8) cytokine by activated neutrophils. Neutrophils from healthy donors were isolated by density gradient (Histopaque® 1077/1119) and incubated with the ketone bodies. Lipoperoxidation was determined as thiobarbituric acid reactive substances (TBARS). The cell viability was evaluated by the release of intracellular lactate dehydrogenase. The release of CXCL8 was measured by ELISA in a 24-h culture of opsonized zymosan-stimulated neutrophils. AcAc, but not β-HOB, provoked a dose-dependent increase in the neutrophil membrane lipoperoxidation (p<0.05; r =0.9915). In the cytotoxicity assay, a dose-dependent release of LDH was observed when the neutrophils were incubated with AcAc in concentrations up to 40 mM (p<0.05). β-HOB was devoid of effect. The release of CXCL8 was inhibited by AcAc and β-HOB in a dose-dependent manner. In conclusion, these results suggest that the accumulation of ketone bodies in diabetic patients could be involved in their usually increased susceptibility to infection.