RESUMO
PURPOSE: Serum nitric oxide (NO) reduction and increased endothelin-1 (ET-1) play a pivotal role in endothelial dysfunction and hypertension. Considering that traditional Mediterranean diet (TMD) reduces blood pressure (BP), the aim of this study was to analyze whether TMD induced changes on endothelial physiology elements such as NO, ET-1 and ET-1 receptors which are involved in BP control. METHODS: Non-smoking women with moderate hypertension were submitted for 1 year to interventions promoting adherence to the TMD, one supplemented with extra virgin olive oil (EVOO) and the other with nuts versus a control low-fat diet (30 participants/group). BP, NO, ET-1 and related gene expression as well as oxidative stress biomarkers were measured. RESULTS: Serum NO and systolic BP (SBP) or diastolic BP (DBP) were negatively associated at baseline, as well as between NO and ET-1. Our findings also showed a DBP reduction with both interventions. A negative correlation was observed between changes in NO metabolites concentration and SBP or DBP after the intervention with TMD + EVOO (p = 0.033 and p = 0.044, respectively). SBP reduction was related to an impairment of serum ET-1 concentrations after the intervention with TMD + nuts (p = 0.008). We also observed changes in eNOS, caveolin 2 and ET-1 receptors gene expression which are related to NO metabolites levels and BP. CONCLUSIONS: The changes in NO and ET-1 as well as ET-1 receptors gene expression explain, at least partially, the effect of EVOO or nuts on lowering BP among hypertensive women.
Assuntos
Biomarcadores/sangue , Pressão Sanguínea , Dieta Mediterrânea , Hipertensão/sangue , Nozes , Azeite de Oliva/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Glicemia/metabolismo , Índice de Massa Corporal , Peso Corporal , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dieta com Restrição de Gorduras , Endotelina-1/sangue , Feminino , Regulação da Expressão Gênica , Humanos , Hipertensão/dietoterapia , Estilo de Vida , Pessoa de Meia-Idade , Óxido Nítrico/sangue , Receptor de Endotelina A/sangue , Receptor de Endotelina A/genética , Fatores de Risco , Inquéritos e Questionários , Triglicerídeos/sangue , Circunferência da CinturaRESUMO
BACKGROUND AND AIM: Hypertension is one of the main cardiovascular risk factors in the elderly. The aims of this work were to evaluate if a one-year intervention with two Mediterranean diets (Med-diet) could decrease blood pressure (BP) due to a high polyphenol consumption, and if the decrease in BP was mediated by plasma nitric oxide (NO) production. METHODS AND RESULTS: An intervention substudy of 200 participants at high cardiovascular risk was carried out within the PREDIMED trial. They were randomly assigned to a low-fat control diet or to two Med-diets, one supplemented with extra virgin olive oil (Med-EVOO) and the other with nuts (Med-nuts). Anthropometrics and clinical parameters were measured at baseline and after one year of intervention, as well as BP, plasma NO and total polyphenol excretion (TPE) in urine samples. Systolic and diastolic BP decreased significantly after a one-year dietary intervention with Med-EVOO and Med-nuts. These changes were associated with a significant increase in TPE and plasma NO. Additionally, a significant positive correlation was observed between changes in urinary TPE, a biomarker of TP intake, and in plasma NO (Beta = 4.84; 95% CI: 0.57-9.10). CONCLUSIONS: TPE in spot urine sample was positively correlated with plasma NO in Med-diets supplemented with either EVOO or nuts. The statistically significant increases in plasma NO were associated with a reduction in systolic and diastolic BP levels, adding to the growing evidence that polyphenols might protect the cardiovascular system by improving the endothelial function and enhancing endothelial synthesis of NO.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Dieta Mediterrânea , Hipertensão/dietoterapia , Óxido Nítrico/sangue , Nozes , Sobrepeso/dietoterapia , Óleos de Plantas/uso terapêutico , Idoso , Biomarcadores/urina , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Estudos de Coortes , Corylus/química , Dieta com Restrição de Gorduras , Feminino , Seguimentos , Humanos , Hipertensão/sangue , Hipertensão/complicações , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Juglans/química , Masculino , Pessoa de Meia-Idade , Nozes/química , Azeite de Oliva , Sobrepeso/complicações , Sobrepeso/metabolismo , Sobrepeso/fisiopatologia , Óleos de Plantas/química , Polifenóis/análise , Polifenóis/uso terapêutico , Polifenóis/urina , Prunus/química , Fatores de Risco , Espanha/epidemiologiaRESUMO
BACKGROUND AND AIMS: Epidemiologic and biological evidence supports an inverse association between polyphenol consumption and the risk of cardiovascular disease (CVD). However, no previous studies have prospectively evaluated the relationship between polyphenol intake and the incidence of CVD in such a comprehensive way. The aim was to evaluate the association between intakes of total polyphenol and polyphenol subgroups, and the risk of major cardiovascular events (myocardial infarction, stroke or death from cardiovascular causes) in the PREDIMED study. METHODS AND RESULTS: The present work is an observational study within the PREDIMED trial. Over an average of 4.3 years of follow-up, there were 273 confirmed cases of CVD among the 7172 participants (96.3%) who completed a validated 137-item food frequency questionnaire (FFQ) at baseline. Polyphenol consumption was calculated by matching food consumption data from the FFQ with the Phenol-Explorer database on polyphenol content of each reported food. After multivariate adjustment, a 46% reduction in risk of CVD risk was observed comparing Q5 vs. Q1 of total polyphenol intake (HR = 0.54; 95% confidence interval [CI] = 0.33-0.91; P-trend = 0.04). The polyphenols with the strongest inverse associations were flavanols (HR = 0.40; CI 0.23-0.72; P-trend = 0.003), lignans (HR = 0.51; CI 0.30-0.86; P-trend = 0.007), and hydroxybenzoic acids (HR = 0.47; CI 0.26-0.86; P-trend 0.02). CONCLUSION: Greater intake of polyphenols, especially from lignans, flavanols, and hydroxybenzoic acids, was associated with decreased CVD risk. Clinical trials are needed to confirm this effect and establish accurate dietary recommendations.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Antioxidantes/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Dieta Mediterrânea , Flavonóis/uso terapêutico , Hidroxibenzoatos/uso terapêutico , Lignanas/uso terapêutico , Fatores Etários , Idoso , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/análise , Antioxidantes/administração & dosagem , Antioxidantes/análise , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Estudos de Coortes , Feminino , Flavonóis/administração & dosagem , Flavonóis/análise , Seguimentos , Humanos , Hidroxibenzoatos/administração & dosagem , Hidroxibenzoatos/análise , Incidência , Lignanas/administração & dosagem , Lignanas/análise , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/prevenção & controle , Nozes/química , Azeite de Oliva , Óleos de Plantas/química , Fatores de Risco , Espanha/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/prevenção & controleRESUMO
AIM: To determine the plasma and saliva levels of IL-6 in patients with bisphosphonate-related osteonecrosis of the jaws (BRONJ) and to investigate whether there is a correlation between more advanced stages of BRONJ and levels of IL-6. MATERIAL AND METHODS: We studied three groups: group 1 consisted of 30 patients with BRONJ due to intravenous bisphosphonates (ivBP), group 2 consisted of 25 patients treated with ivBP but without BRONJ, and group 3 consisted of 15 healthy controls. In each case, we assayed plasma and saliva IL-6 samples using an ELISA test. RESULTS: Significantly, higher IL-6 values were found in both saliva and plasma in group 1 vs groups 2 and 3 (P < 0.01). Group 1 showed no differences in plasma or saliva IL-6 according to patient gender (P > 0.05), type of tumor, BRONJ location, etiology of BRONJ, or disease stage (P > 0.05). We found higher plasma and saliva IL-6 values in the more advances stages of BRONJ, although the differences were not statistically significant. CONCLUSIONS: Plasma and saliva IL-6 values were higher in our patients with BRONJ than in controls and therefore might be a useful tool for monitoring the severity of BRONJ.
Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/metabolismo , Interleucina-6/análise , Interleucina-6/sangue , Saliva/química , Idoso , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/sangue , Difosfonatos/administração & dosagem , Feminino , Humanos , MasculinoRESUMO
BACKGROUND AND AIMS: Epidemiological data have shown an inverse association between the consumption of polyphenol-rich foods and the risk of cardiovascular disease or overall mortality. A comprehensive estimation of individual polyphenol intake in nutritional cohorts is needed to gain a better understanding of this association. The aim of this study was to estimate the quantitative intake of polyphenols and the major dietary sources in the PREDIMED (PREvención con DIeta MEDiterránea) cohort using individual food consumption records. METHODS AND RESULTS: The PREDIMED study is a large, parallel-group, multicentre, randomised, controlled 5-year feeding trial aimed at assessing the effects of the Mediterranean diet on the primary prevention of cardiovascular disease. A total of 7200 participants, aged 55-80 years, completed a validated 1-year food frequency questionnaire (FFQ) at baseline. Polyphenol consumption was calculated by matching food consumption data from the FFQ with the recently developed Phenol-Explorer database on polyphenol content in foods. The mean total polyphenol intake was 820 ± 323 mg day⻹ (443 ± 218 mg day⻹ of flavonoids and 304 ± 156 mg day⻹ of phenolic acids). Hydroxycinnamic acids were the phenolic group with the highest consumption and 5-caffeoylquinic acid was the most abundantly ingested individual polyphenol. The consumption of olives and olive oil was a differentiating factor in the phenolic profile of this Spanish population compared with other countries. CONCLUSION: In Mediterranean countries, such as Spain, the main dietary source of polyphenols is coffee and fruits, but the most important differentiating factor with respect to other countries is the consumption of polyphenols from olives and olive oil.
Assuntos
Envelhecimento , Doenças Cardiovasculares/prevenção & controle , Dieta Mediterrânea , Alimento Funcional/análise , Olea , Óleos de Plantas/uso terapêutico , Polifenóis/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etnologia , Ácido Clorogênico/análogos & derivados , Ácido Clorogênico/análise , Ácido Clorogênico/uso terapêutico , Café/química , Estudos de Coortes , Ácidos Cumáricos/análise , Ácidos Cumáricos/uso terapêutico , Dieta Mediterrânea/etnologia , Feminino , Flavonoides/análise , Flavonoides/uso terapêutico , Frutas/química , Humanos , Masculino , Pessoa de Meia-Idade , Olea/química , Azeite de Oliva , Fenóis/análise , Fenóis/uso terapêutico , Óleos de Plantas/química , Polifenóis/análise , Ácido Quínico/análogos & derivados , Ácido Quínico/análise , Ácido Quínico/uso terapêutico , Risco , Espanha/epidemiologiaRESUMO
BACKGROUND AND AIM: Hypertension is a major public health problem and a leading cause of death and disability in both developed and developing countries, affecting one-quarter of the world's adult population. Our aim was to evaluate whether the consumption of gazpacho, a Mediterranean vegetable-based cold soup rich in phytochemicals, is associated with lower blood pressure (BP) and/or reduced prevalence of hypertension in individuals at high cardiovascular risk. METHODS AND RESULTS: We selected 3995 individuals (58% women, mean age 67 y) at high cardiovascular risk (81% hypertensive) recruited into the PREDIMED study. BP, weight, and dietary and physical activity data were collected. In multivariate linear regression analyses, after adjustment, moderate and high gazpacho consumption categories were associated with reduced mean systolic BP of -1.9 mm Hg [95% confidence interval (CI): -3.4; -0.6] and -2.6 mm Hg (CI: -4.2; -1.0), respectively, and reduced diastolic BP of -1.5 mm Hg (CI: -2.3; -0.6) and -1.9 mm Hg (CI: -2.8; -1.1). By multiple-adjusted logistic regression analysis, gazpacho consumption was associated with a lower prevalence of hypertension, with OR = 0.85 (CI: 0.73; 0.99) for each 250 g/week increase and OR = 0.73 (CI: 0.55; 0.98) for high gazpacho consumption groups compared to the no-consumption group. CONCLUSIONS: Gazpacho consumption was inversely associated with systolic and diastolic BP and prevalence of hypertension in a cross-sectional Mediterranean population at high cardiovascular risk. The association between gazpacho intake and reduction of BP is probably due to synergy among several bioactive compounds present in the vegetable ingredients used to make the recipe.
Assuntos
Envelhecimento , Doenças Cardiovasculares/epidemiologia , Frutas , Alimento Funcional , Hipertensão/prevenção & controle , Solanum lycopersicum , Verduras , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Estudos de Coortes , Culinária , Estudos Transversais , Dieta Mediterrânea , Feminino , Frutas/química , Alimento Funcional/análise , Humanos , Hipertensão/dietoterapia , Hipertensão/epidemiologia , Solanum lycopersicum/química , Masculino , Pessoa de Meia-Idade , Compostos Fitoquímicos/uso terapêutico , Prevalência , Fatores de Risco , Espanha/epidemiologia , Verduras/químicaRESUMO
BACKGROUND AND AIMS: Dietary factors are critical for the prevention and treatment of hypertension, but data on the effects of specific nutrients on blood pressure (BP) are scarce. The aim of this study was to assess the relationship between total polyphenol excretion (TPE) in urine, as an objective measurement of total polyphenol intake and BP in an elderly population at high cardiovascular risk. METHODS AND RESULTS: Cross-sectional substudy of 589 high-risk participants entering in the PREDIMED trial. BP was measured and TPE was determined in urine by Folin-Ciocalteu assay. A significant positive association was observed between TPE in urine and daily intake of fruit and vegetables (F&V), coffee or wine after adjusting for potential confounders. The intake of 100 g of F&V (Beta=0.150;P<0.001) had a greater contribution to TPE than 100 mL of coffee (Beta=0.141;P=0.001), and the latter two foods contributed more than the consumption of 100 mL of wine (Beta=0.120;P=0.019). An inverse association was observed between urinary TPE and the prevalence of hypertension. Participants in the highest quartile of urinary TPE had a reduced prevalence of hypertension compared to those in the lowest quartile (Odds Ratio=0.64; 95% confidence interval 0.45 to 0.92; P=0.015). Systolic and diastolic BP were inversely associated with urinary TPE after adjustment for potential confounders (P=0.024 and P=0.003, respectively). CONCLUSIONS: Polyphenol intake, assessed via TPE in urine, was negatively associated with BP levels and prevalence of hypertension in an elderly Mediterranean population at high cardiovascular risk. Participants with the highest intake of polyphenol-rich foods showed the lowest BP measurements.
Assuntos
Pressão Sanguínea , Dieta , Flavonoides/urina , Hipertensão/epidemiologia , Fenóis/urina , Idoso , Café , Estudos Transversais , Feminino , Frutas , Humanos , Modelos Lineares , Masculino , Região do Mediterrâneo/epidemiologia , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Polifenóis , Prevalência , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Inquéritos e Questionários , Verduras , VinhoRESUMO
Human very-low-density lipoproteins (VLDL) were subfractionated by heparin-Sepharose chromatography into an unbound (A) and three bound (B, C and D) populations at increasing ionic strengths. Subfractions were characterized regarding their chemical composition and efficiency of triacylglycerol hydrolysis by rat adipose tissue LPL. The triacylglycerol content decreased, whereas the cholesterol and protein contents increased from subfractions A and B to subfraction D. VLDL-D showed the highest apo E/apo C ratio, though all the subfractions contained appreciable apo E. Appearance of VLDL-A resulted from exceeding the binding capacity of the column, since practically all its particles eluted at positions of bound VLDL under re-chromatography. Subfractions B, C and D stimulated LPL activity on emulsified tri[14C]oleoylglycerol to a similar extent, indicating that their apo C-II content was equally effective activating LPL. Incubation of tri[14C]oleoylglycerol labeled VLDL subfractions with fat pad pieces in the presence or absence of heparin resulted in greater hydrolysis and fatty acid uptake for VLDL-B and -C than for VLDL-D, a pattern observed over a wide range of LPL activities in the media. We conclude: (1) any VLDL particle can interact with heparin, which is consistent with the presence of apo E in all the subfractions, and (2) triacylglycerols in apo E-rich VLDL are less efficiently hydrolyzed by LPL than those in apo E-poor particles. We propose that richness in apo E impairs LPL action upon VLDL and decreases the rate of delivery of fatty acids to peripheral tissues.
Assuntos
Tecido Adiposo/enzimologia , Lipase Lipoproteica/metabolismo , Lipoproteínas VLDL/sangue , Animais , Apolipoproteínas E/análise , Radioisótopos de Carbono , Cromatografia em Agarose , Epididimo/enzimologia , Humanos , Hidrólise , Lipoproteínas VLDL/química , Lipoproteínas VLDL/isolamento & purificação , Masculino , Ratos , Sefarose/análogos & derivados , Triglicerídeos/metabolismoRESUMO
The effect of rifamycin SV on metabolic performance and cell viability was studied using isolated hepatocytes from fed, starved and glutathione (GSH) depleted rats. The relationships between GSH depletion, nutritional status of the cells, glucose metabolism, lactate dehydrogenase (LDH) leakage and malondialdehyde (MDA) production in the presence of rifamycin SV and transition metal ions was investigated. Glucose metabolism was impaired in isolated hepatocytes from both fed and starved animals, the effect is dependent on the rifamycin SV concentration and is enhanced by copper (II). Oxygen consumption by isolated hepatocytes from starved rats was also increased by copper (II) and a partial inhibition due to catalase was observed. Cellular GSH levels which decrease with increasing the rifamycin SV concentration were almost depleted in the presence of copper (II). A correlation between GSH depletion and LDH leakage was observed in fed and starved cells. Catalase induced a slight inhibition of the impairment of gluconeogenesis, GSH depletion and LDH leakage in starved hepatocytes incubated with rifamycin SV, iron (II) and copper (II) salts. Lipid peroxidation measured as MDA production by isolated hepatocytes was also augmented by rifamycin SV and copper (II), especially in hepatic cells isolated from starved and GSH depleted rats. Higher cytotoxicity was observed in isolated hepatocytes from fasted animals when compared with fed or GSH depleted animals. It seems likely that in addition to GSH level, there are other factors which may have an influence on the susceptibility of hepatic cells towards xenobiotic induced cytotoxicity.
Assuntos
Sobrevivência Celular/efeitos dos fármacos , Cobre/metabolismo , Ferro/metabolismo , Fígado/efeitos dos fármacos , Rifamicinas/farmacologia , Animais , Catalase/metabolismo , Gluconeogênese/efeitos dos fármacos , Glutationa/metabolismo , L-Lactato Desidrogenase/metabolismo , Peroxidação de Lipídeos , Fígado/citologia , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , Oxirredução , Consumo de Oxigênio/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Tiobarbitúricos/metabolismoRESUMO
Entry of metabolic 14CO2 into urea is shown to occur more readily than it equilibrates with the general pool of cellular plus extracellular bicarbonate plus CO2. Since the sites of CO2 production (pyruvate dehydrogenase and oxoglutarate dehydrogenase) and of fixation (carbamoylphosphate synthetase) are intramitochondrial, it is likely that the fixation of CO2 is also more rapid than its equilibration with the cytoplasmic pool of bicarbonate plus CO2. This observation may point to a more general problem concerning the interpretation of isotope data, when compartmentation or proximity of sites of production and utilisation of metabolites may result in the isotope following a preferred pathway.
Assuntos
Bicarbonatos/metabolismo , Dióxido de Carbono/metabolismo , Fígado/metabolismo , Alanina/metabolismo , Animais , Radioisótopos de Carbono , Jejum , Glutamina/metabolismo , Lactatos/metabolismo , Ácido Láctico , Ratos , Ratos EndogâmicosRESUMO
Chronic lymphocytic leukemia (CLL) is a neoplastic disease susceptible to antioxidant enzyme alterations and oxidative stress. We have examined the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), and the oxidized/reduced glutathione (GSSG/GSH) ratio together with the levels of malondialdehyde (MDA) and 8-oxo-2'-deoxyguanosine (8-oxo-dG) in lymphocytes of CLL patients and compared them with those of normal subjects of the same age. SOD and CAT activity decreased in CLL lymphocytes while GPx activity increased. GSH content of CLL lymphocytes also increased, and GSSG concentration remained constant. Thus, a reduced GSSG/GSH ratio was obtained. The oxidation product MDA, and the damaged DNA base 8-oxo-dG were also increased in CLL. The observed changes in enzyme activities, GSSG/GSH ratio, and MDA were significantly enhanced as the duration of the disease increased in years. The results support a predominant oxidative stress status in CLL lymphocytes and emphasize the role of the examined parameters as markers of the disease evolution.
Assuntos
Desoxiguanosina/biossíntese , Glutationa/metabolismo , Leucemia Linfocítica Crônica de Células B/metabolismo , Malondialdeído/metabolismo , Oxirredutases/metabolismo , 8-Hidroxi-2'-Desoxiguanosina , Idoso , Antioxidantes/metabolismo , Catalase/metabolismo , Dano ao DNA , DNA de Neoplasias/metabolismo , Desoxiguanosina/análogos & derivados , Feminino , Glutationa Peroxidase/metabolismo , Humanos , Peroxidação de Lipídeos , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Superóxido Dismutase/metabolismoRESUMO
The effect of two naturally occurring thiols, such as cysteine and homocysteine, has been examined for their ability to induce deoxyribose degradation and DNA damage. Copper(II) ions have been added to incubation mixtures and oxygen consumption measurements have been performed in order to correlate the observed damaging effects with the rate of metal catalyzed thiol oxidation. Ascorbic acid plus copper has been used as a positive control of deoxyribose and DNA oxidation due to reactive oxygen species. Cysteine or homocysteine in the presence of copper ions induce the degradation of deoxyribose and the yield of 8-hydroxy-2'-deoxyguanosine (8-OHdG), although important differences are observed between the two thiols tested, homocysteine being less reactive than cysteine. DNA cleavage is induced by cysteine in the presence of copper(II) ions but not by homocysteine. Catalase and thiourea, but not superoxide dismutase (SOD), were shown to inhibit the damaging effects of cysteine on deoxyribose or DNA suggesting that H(2)O(2) and *OH radicals are responsible for the observed induced damage. The results indicate that there are differences between the damaging effects of the two thiols tested towards deoxyribose and DNA damage. The pathophysiological importance will be discussed.
Assuntos
Cisteína/farmacologia , Dano ao DNA/efeitos dos fármacos , Desoxiguanosina/análogos & derivados , Desoxirribose/metabolismo , Homocisteína/farmacologia , 8-Hidroxi-2'-Desoxiguanosina , Animais , Ácido Ascórbico/farmacologia , Catalase/química , Bovinos , Cobre/metabolismo , Desoxiguanosina/metabolismo , Eletroforese em Gel de Ágar , Oxirredução , Consumo de Oxigênio , Espécies Reativas de Oxigênio , Espectrofotometria , Superóxido Dismutase/química , Tioureia/química , Timo/químicaRESUMO
The effect of rifamycin SV on the formation of 8-hydroxy-2'-deoxyguanosine (8-0HdG) has been investigated in vitro and in vivo. Oxidative modification of 2'-deoxyguanosine has been measured as an indication of DNA damage using high-performance liquid chromatography with electrochemical detection. Rifamycin SV in the presence of copper(II) ions induces the formation of 8-0HdG in calf thymus DNA. The effect is enhanced by increasing the antibiotic concentration and inhibited by catalase and hydroxyl radical (.0H) scavengers, such as thiourea and ethanol, in a rifamycin SV concentration-dependent manner. The reduced glutathione (GSH) inhibits DNA damage, and this effect is proportional to the final concentration of the tripeptide in the incubation medium. A significant increase in the formation of 8-0HdG and of malondialdehyde (MDA) in rat liver DNA was observed only in GSH-depleted animals after 5 days of rifamycin SV treatment. These results support the involvement of hydrogen peroxide (H2(0)2) and .0H in the mechanism of the oxidative modification of DNA achieved by rifamycin SV. The role of other reactive species and the antioxidant properties of GSH against oxidative damage is also discussed.
Assuntos
Dano ao DNA , Desoxiguanosina/farmacologia , Rifamicinas/farmacologia , Animais , Antioxidantes/farmacologia , Bovinos , Cobre/farmacologia , Radicais Livres , Glutationa/farmacologia , Fígado , Masculino , Ratos , Ratos Wistar , TimoRESUMO
Long-term exposure to high doses of caffeine affects several aspects of nitrogen metabolism, such as purine, pyrimidine and urea synthesis. However, little is known about the mechanisms of these changes and if they occur at shorter term. We have studied in isolated hepatocytes: 1) the in vitro effect of high doses of caffeine on amino acid levels, 2) the main destination of ammonia and carbon chains from amino acid catabolism, and 3) the cytosolic and mitochondrial redox states. We have found that, whereas it has a small effect on urea synthesis and on the levels of the cofactors and intermediates, it decreases the levels of several amino acids, the gluconeogenesis and the redox state. Our results suggest that a longer exposure to caffeine is necessary to affect the normal functions of some metabolic pathways.
Assuntos
Cafeína/farmacologia , Fígado/efeitos dos fármacos , Aminoácidos/metabolismo , Animais , Citosol/efeitos dos fármacos , Gluconeogênese/efeitos dos fármacos , Técnicas In Vitro , Fígado/citologia , Masculino , Mitocôndrias Hepáticas/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Ureia/biossínteseRESUMO
An increase in urea synthesis has been found in rats administered large doses of caffeine. A parallel increase in urea biosynthesis was also found in hepatocytes isolated from caffeine-treated rats, which confirms a greater capacity for urea synthesis induced by caffeine. This increase appeared only after some days of caffeine treatment; during the first days there was no increase in serum urea levels or in in vitro studies of urea synthesis in isolated hepatocytes. However, no appreciable changes were found in either cytosolic or mitochondrial redox states, or in ATP levels in in vivo and in vitro studies. A parallelism was observed between the decreased amino acid levels in caffeine-treated rats and in isolated hepatocytes incubated with different concentrations of caffeine. Several possible mechanisms to explain these findings are considered in the discussion.
Assuntos
Cafeína/farmacologia , Fígado/efeitos dos fármacos , Ureia/biossíntese , Trifosfato de Adenosina/metabolismo , Aminoácidos/metabolismo , Animais , Técnicas In Vitro , Corpos Cetônicos/metabolismo , Fígado/enzimologia , Fígado/metabolismo , Masculino , Ratos , Ratos EndogâmicosRESUMO
The dependence of gluconeogenesis and O2 uptake on PO2 in isolated rat hepatocytes is presented. Maintenance of steady-state PO2 was achieved with an oxystat system (Biochem. J. 236: 765-769, 1986). O2 uptake showed a half-maximal (K0.5) value of 0.5 Torr PO2, whereas the glucose synthesis rate was half-maximal at 1.2 Torr PO2. Halothane at concentrations greater than 1 mM exerted a parallel inhibition of O2 uptake and glucose synthesis at all PO2 levels studied. In contrast, at halothane concentrations less than 1 mM, inhibition of glucose synthesis occurred only at less than 20 Torr PO2. At these low concentrations, halothane was without significant effects on cellular O2 uptake. In isolated mitochondria, inhibition of O2 uptake was already half-maximal at a halothane concentration of 0.5 mM. In this subcellular system the inhibitory effect of halothane was independent of PO2. These results demonstrate that the critical PO2 at which cellular O2 utilization begins to decrease and the PO2 at which glucose synthesis begins to decrease are comparable; both PO2 levels are approximately 5 Torr. The metabolic zonation of the liver lobule is discussed in view of the results presented.
Assuntos
Gluconeogênese , Halotano/farmacologia , Fígado/metabolismo , Oxigênio/fisiologia , Animais , Gluconeogênese/efeitos dos fármacos , Técnicas In Vitro , Cinética , Fígado/efeitos dos fármacos , Masculino , Mitocôndrias Hepáticas/metabolismo , Oxigênio/antagonistas & inibidores , Consumo de Oxigênio/efeitos dos fármacos , Ratos , Ratos EndogâmicosRESUMO
Many human cancers present deletions of the short arm of chromosome 17, which includes the TP53 locus. We detected a new polymorphism in intron 2 of the TP53 gene using PCR-SSCP and used this polymorphic site as a marker to detect loss of heterozygosity in 135 human tumors (73 soft tissue sarcomas, and 48 colorectal and 14 bladder carcinomas). Heterozygosity for this site was 41.5% in this study group and tumor-specific loss of alleles occurred in 43% of informative cases. Allelic losses were more frequently detected at this site than at that in which restriction fragment length polymorphism (RFLP) is located, as detected by the pHp53B probe. It is concluded that this novel approach has several advantages, including detection of a high incidence of informative cases and minimal tissue requirements.
Assuntos
Genes p53/genética , Íntrons/genética , Polimorfismo Genético/genética , Sequência de Bases , Deleção Cromossômica , Neoplasias Colorretais/genética , Heterozigoto , Humanos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Polimorfismo Conformacional de Fita Simples , Sarcoma/genética , Neoplasias de Tecidos Moles/genética , Neoplasias da Bexiga Urinária/genéticaRESUMO
The effect of t-butyl hydroperoxide (t-BOOH) on the induction of the Major Histocompatibility Complex (MHC) class I genes has been studied in two cell clones (B9 and G2) of the methylcholanthrene-induced murine fibrosarcoma GR9. These two clones were selected based on their different biological and biochemical behavior specially related to their tumor induction capability when injected into a BALB/c mouse. t-BOOH (0.125 mM) induced the expression of H-2 molecules in both cell clones. In B9 cell clone, in which MHC basal expression is very low or absent, t-BOOH significantly induced H-2Kd, H-2Dd and H-2Ld molecules. In G2 cell clone the expression of MHC class I genes was also enhanced by the xenobiotic, the effect being especially significant on the H-2Ld molecule which is not expressed under basal conditions. H-2 molecules expression was accompanied by the activation of the transactivator factor NF kappa B. These results suggest that oxidative stress may modulate the antigen expression of tumor cells and thus the immune response of the host organism. Basal levels of oxidative parameters, such as anti-oxidant enzymes, malondialdehyde (MDA) and the DNA damaged base 8-hydroxy-2'-deoxyguanosine (8-OHdG), showed differences between the two fibrosarcoma cell clones.
Assuntos
Desoxiguanosina/análogos & derivados , Fibrossarcoma/metabolismo , Regulação da Expressão Gênica , Antígenos de Histocompatibilidade Classe I/metabolismo , Complexo Principal de Histocompatibilidade/genética , Estresse Oxidativo , Células 3T3 , 8-Hidroxi-2'-Desoxiguanosina , Animais , Catalase/metabolismo , Desoxiguanosina/metabolismo , Ensaio de Desvio de Mobilidade Eletroforética , Fibrossarcoma/induzido quimicamente , Fibrossarcoma/genética , Citometria de Fluxo , Regulação da Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Antígenos de Histocompatibilidade Classe I/genética , Malondialdeído/metabolismo , Metilcolantreno/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Células Tumorais Cultivadas , terc-Butil Hidroperóxido/farmacologiaRESUMO
A simple microassay for the determination of hydrazine in laboratory samples is presented. The colored product of the reaction of p-dimethylaminobenzaldehyde with hydrazine was tested at 470 nm using double-beam mode in different samples. Internal standards and data on blood serum, liver, and brain of rats treated with hydrazine or isoniazid are presented. The tissue glutathione content of these rats was determined, and the possible implication of glutathione in the brain toxicity of hydrazine is discussed.
Assuntos
Química Encefálica/efeitos dos fármacos , Glutationa/metabolismo , Hidrazinas/análise , Isoniazida/farmacologia , Fígado/metabolismo , Animais , Hidrazinas/farmacologia , Fígado/efeitos dos fármacos , Masculino , RatosRESUMO
Olive oil phenolic compounds are generally believed to have beneficial antioxidant effects, but little is known about characteristics of their postprandial bioavailability in natural olive oil at real-life doses. The aim of the present study was to determine the concentrations of olive oil phenolic compounds in urine collected over 24 h (24-h urine) after a bolus ingestion of 25 ml of olive oil with different phenolic content, and to demonstrate the effect of this real-life olive oil dose on postprandial levels of blood lipids and oxidative stress biomarkers, as well as to examine the beneficial effects of olive oil phenols. Oral fat loads of 25 ml olive oil with high, moderate, and low phenolic content were administered to 12 healthy male volunteers in a randomized, controlled, crossover trial. Tyrosol and hydroxytyrosol were absorbed in a dose-dependent manner according to the phenolic content of the olive oil administered. The administered dose of 25 ml, which is close to that used daily in Mediterranean countries, did not induce significant postprandial lipemia nor did it promote an increase of in vivo oxidation markers. With regard to plasma antioxidant enzymes, glutathione peroxidase activity decreased postprandially after low phenolic content olive oil ingestion; however this was not observed after intake of moderate and high phenolic content olive oils. The phenolic content of the olive oils administered may account for the protection of the endogenous antioxidant defenses at postprandial state after ingestion of moderate and high phenolic content olive oils.