RESUMO
OBJECTIVE: There is considerable controversy about what constitutes optimal zinc intakes in patients with type 2 diabetes mellitus. Several studies suggest that higher zinc intakes improve vascular function and decrease oxidative damage. We aimed to assess the effects of zinc supplementation using a range of reliable biomarkers of oxidative damage and vascular function in patients with type 2 diabetes. METHODS: Forty male type 2 diabetic patients were supplemented either with 240 mg/day of zinc as zinc gluconate (n=20) or with placebo (n=20) for 3 months. Blood and spot urine samples were taken at baseline, days 3 and 7, months 1, 2 and 3 during supplementation and 1 month after cessation. Serum zinc, reliable biomarkers of oxidative damage (F(2)-isoprostanes, neuroprostanes, cholesterol oxidation products, allantoin) as well as hydroxyeicosatetraenoic acid products and vascular-related indices (augmentation index, pulse wave velocity and aortic pressure) were measured. RESULTS: Despite significantly higher levels of serum zinc in the treatment group, markers of oxidative damage, levels of hydroxyeicosatetraenoic acid products and vascular indices were unchanged by zinc supplementation during the four-month study period. CONCLUSION: Improving the zinc status in patients with type 2 diabetes with normal zinc levels did not have any impact on oxidative damage and vascular function, and such supplementation may not be generally beneficial in these individuals.
Assuntos
Zinco/administração & dosagem , Idoso , Alantoína/sangue , Colesterol/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Suplementos Nutricionais , F2-Isoprostanos/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Zinco/sangueRESUMO
BACKGROUND AND PURPOSE: We investigated changes in oxidative damage after ischemic stroke using multiple biomarkers. METHODS: Serial blood and urine samples of ischemic stroke subjects and age-matched control subjects were assayed for F2-isoprostanes, hydroxyeicosatetraenoic acid products, F4-neuroprostanes, 24-hydroxycholesterol, allantoin, and urate. RESULTS: Sixty-six stroke subjects (mean age, 65 years; median National Institutes of Health Stroke Scale 17) and 132 control subjects were recruited. A bimodal pattern of change was observed in plasma and urinary F2-isoprostanes and plasma 24-hydroxycholesterol. The rise in plasma hydroxyeicosatetraenoic acid products, F4-neuroprostanes, and allantoin was highest 6 to 12 hours after stroke onset, whereas plasma urate was significantly lower than controls on Days 1 to 3. After adjusting for age and baseline National Institutes of Health Stroke Scale, baseline plasma esterified hydroxyeicosatetraenoic acid products (OR, 1.01; 95% CI, 1.01 to 1.02), plasma urate (1.01; 1.00 to 1.01), and plasma free F4-neuroprostanes (2.73; 1.76 to 3.93) were associated with 90-day good functional recovery (modified Rankin Scale ≤1). CONCLUSIONS: Multiple markers of oxidative damage are increased immediately after stroke and remain elevated for several days. Recognition of these temporal changes may help design better antioxidant treatment trials for acute ischemic stroke.
Assuntos
Isquemia Encefálica/metabolismo , F2-Isoprostanos/metabolismo , Hidroxicolesteróis/metabolismo , Estresse Oxidativo/fisiologia , Acidente Vascular Cerebral/metabolismo , Idoso , Alantoína/metabolismo , Biomarcadores/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuroprostanos/metabolismo , OxirreduçãoRESUMO
Cigarette smoking predisposes to the development of multiple diseases involving oxidative damage. We measured a range of oxidative damage biomarkers to understand which differ between smokers and nonsmokers and if the levels of these biomarkers change further during the act of smoking itself. Despite overnight abstinence from smoking, smokers had higher levels of plasma total and esterified F(2)-isoprostanes, hydroxyeicosatetraenoic acid products (HETEs), F(4)-neuroprostanes, 7-ketocholesterol, and 24- and 27-hydroxycholesterol. Levels of urinary F(2)-isoprostanes, HETEs, and 8-hydroxy-2'-deoxyguanosine were also increased compared with age-matched nonsmokers. Several biomarkers (plasma free F(2)-isoprostanes, allantoin, and 7ß-hydroxycholesterol and urinary F(2)-isoprostane metabolites) were not elevated. The smokers were then asked to smoke a cigarette; this acute smoking elevated plasma and urinary F(2)-isoprostanes, plasma allantoin, and certain cholesterol oxidation products compared to presmoking levels, but not plasma HETEs or urinary 8-hydroxy-2'-deoxyguanosine. Smokers showed differences in plasma fatty acid composition. Our findings confirm that certain oxidative damage biomarkers are elevated in smokers even after a period of abstinence from smoking, whereas these plus some others are elevated after acute smoking. Thus, different biomarkers do not measure identical aspects of oxidative stress.
Assuntos
Alantoína/sangue , F2-Isoprostanos/metabolismo , Hidroxicolesteróis/metabolismo , Ácidos Hidroxieicosatetraenoicos/metabolismo , Estresse Oxidativo , Fumar/metabolismo , 8-Hidroxi-2'-Desoxiguanosina , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/urina , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Desoxiguanosina/urina , F2-Isoprostanos/sangue , F2-Isoprostanos/urina , Radicais Livres , Humanos , Hidroxicolesteróis/sangue , Ácidos Hidroxieicosatetraenoicos/sangue , Ácidos Hidroxieicosatetraenoicos/urina , Cetocolesteróis/sangue , Cetocolesteróis/metabolismo , Masculino , Pessoa de Meia-Idade , Fumar/sangue , Fumar/urinaRESUMO
OBJECTIVE: The role of oxidative damage in the pathogenesis of metabolic syndrome is poorly understood. RESEARCH DESIGN AND METHODS: A detailed cross-sectional study was performed to assess the relationship between lipid oxidation products, gamma-glutamyltransferase, high-sensitivity C-reactive protein (hs-CRP), and phospholipase activities with respect to the metabolic status in a cohort of otherwise healthy individuals. RESULTS: A total of 179 individuals (87 men and 92 women) aged 43 +/- 14 years (mean +/- SD) participated in this study. There were no differences in the levels of plasma F(2)-isoprostanes, hydroxyeicosatetraenoic acids, cholesterol oxidation products, and phospholipase activities in individuals with features of metabolic syndrome. In multivariate analyses, serum hs-CRP was a consistent independent predictor of metabolic syndrome. CONCLUSIONS: Minimal changes were observed in multiple markers of oxidative damage in a well-characterized cohort of individuals with features of metabolic syndrome.
Assuntos
Biomarcadores/metabolismo , Síndrome Metabólica/metabolismo , Estresse Oxidativo/fisiologia , Adulto , Proteína C-Reativa/metabolismo , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Peroxidação de Lipídeos/fisiologia , Masculino , Síndrome Metabólica/diagnóstico , Pessoa de Meia-Idade , Fosfolipases A2/sangue , Valor Preditivo dos Testes , gama-Glutamiltransferase/sangueRESUMO
Oxidative damage has been implicated in the pathogenesis of Parkinson disease (PD) but the literature data are confusing. Using products of lipid and DNA oxidation measured by accurate methods, we assessed the extent of oxidative damage in PD patients. The levels of plasma F(2)-isoprostanes (F(2)-IsoPs), hydroxyeicosatetraenoic acid products (HETEs), cholesterol oxidation products, neuroprostanes (F(4)-NPs), phospholipase A(2) (PLA(2)) and platelet activating factor-acetylhydrolase (PAF-AH) activities, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), and serum high-sensitivity C-reactive protein were compared in 61 PD patients and 61 age-matched controls. The levels of plasma F(2)-IsoPs, HETEs, 7beta-and 27-hydroxycholesterol, 7-ketocholesterol, F(4)-NPs, and urinary 8-OHdG were elevated, whereas the levels of plasma PLA(2) and PAF-AH activities were lower, in PD patients compared to controls (p< 0.05). The levels of plasma F(2)-IsoPs, HETEs, and urinary 8-OHdG were higher in the early stages of PD (p trend< 0.05). There was a significant negative correlation between the cumulative intake of levodopa and urinary 8-OHdG (r= -0.305, p= 0.023) and plasma total HETEs (r= -0.285, p= 0.043). Oxidative damage markers are systemically elevated in PD, which may give clues about the relation of oxidative damage to the onset and progression of PD.
Assuntos
Biomarcadores/metabolismo , Estresse Oxidativo , Doença de Parkinson/sangue , Doença de Parkinson/diagnóstico , Idoso , Proteína C-Reativa/química , Estudos de Casos e Controles , Colesterol/química , DNA/química , Progressão da Doença , F2-Isoprostanos/química , Feminino , Humanos , Ácidos Hidroxieicosatetraenoicos/química , Levodopa/farmacologia , Lipídeos/química , Masculino , Pessoa de Meia-Idade , Oxigênio/química , Doença de Parkinson/patologiaRESUMO
AIM OF STUDY: Oxidative stress is involved in stroke. In particular, Chinese Herbal Medicine with antioxidant properties is believed to have potential therapeutic effect. In this study, neuroprotective effects of purified Herba Leonuri (pHL) were evaluated in Wistar rats undergone middle cerebral artery occlusion (MCAO). MATERIALS AND METHODS: The rats were treated with their respective treatments for 2 weeks prior to the MCAO, continually treated for another 7 days after MCAO. During the post-surgery treatment period, neurological deficit score was measured. At the end of treatment, animals were sacrificed and samples were collected for analysis of infarct volume, apoptosis and antioxidant analysis. RESULTS: Under the treatment of pHL, the infarct volume was reduced significantly from 20.75+/-0.03% to 15.19+/-0.02% (p<0.05). The neurological impairment was alleviated to 1.82 as compared to vehicle (2.43). Plasma antioxidant concentration was increased from 0.31+/-0.03 mM to 0.42+/-0.05 mM (p<0.05). DNA oxidative damage was reduced to 1.19+/-0.03 in stroke pHL treated group (p<0.05 as compared to vehicle group, 1.78+/-0.03). pHL could reduce the level of apoptosis and also the pro-apoptotic proteins, but increase the level of anti-apoptotic proteins. CONCLUSION: pHL is believed to have promising therapeutic effect for stroke treatment through antioxidant mechanisms.
Assuntos
Antioxidantes/farmacologia , Encéfalo/efeitos dos fármacos , Medicamentos de Ervas Chinesas/uso terapêutico , Infarto da Artéria Cerebral Média/tratamento farmacológico , Leonurus/química , Fármacos Neuroprotetores/uso terapêutico , Fitoterapia , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Atividade Motora/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos Wistar , Acidente Vascular Cerebral/tratamento farmacológicoRESUMO
Oxidative stress may be important in the pathogenesis of dengue infection. Using accurate markers of oxidative damage, we assessed the extent of oxidative damage in dengue patients. The levels of hydroxyeicosatetraenoic acid products (HETEs), F(2)-isoprostanes (F(2)-IsoPs), and cholesterol oxidation products (COPs) were measured in 28 adult dengue patients and 28 age-matched study controls during the febrile, defervescent, and convalescent stages of infection. We compared the absolute and the percentage change in these markers in relation to key clinical parameters and inflammatory markers. The levels of total HETEs and total HETEs/arachidonate, total F(2)-IsoPs/arachidonate, and COPs/cholesterol were higher during the febrile compared to the convalescent level. Total HETEs correlated positively with admission systolic blood pressure (r=0.52, p<0.05), whereas an inverse relationship was found between 7beta-hydroxycholesterol and systolic and diastolic blood pressure (r=-0.61 and -0.59, respectively, p<0.01). The urinary F(2)-IsoP level was higher in urine during the febrile stage compared to the convalescent level. Despite lower total cholesterol levels during the febrile stage compared to convalescent levels, a higher percentage of cholesterol was found as COPs (7beta-, 24-, and 27-hydroxycholesterol). The levels of platelet-activating factor-acetylhydrolase activity, vascular cellular adhesion molecule-1, tumor necrosis factor-alpha, and high-sensitivity C-reactive protein were higher during the febrile stage compared to their convalescent levels (p<0.01). Markers of oxidative damage are altered during the various stages of dengue infection.
Assuntos
Biomarcadores/sangue , Colesterol/sangue , Vírus da Dengue/fisiologia , Dengue/fisiopatologia , F2-Isoprostanos/sangue , Ácidos Hidroxieicosatetraenoicos/sangue , 1-Alquil-2-acetilglicerofosfocolina Esterase/genética , 1-Alquil-2-acetilglicerofosfocolina Esterase/metabolismo , Adulto , Idoso , Biomarcadores/urina , Pressão Sanguínea , Proteína C-Reativa/genética , Proteína C-Reativa/metabolismo , Colesterol/análogos & derivados , Colesterol/urina , Dengue/sangue , Dengue/genética , Vírus da Dengue/patogenicidade , Progressão da Doença , F2-Isoprostanos/urina , Feminino , Regulação da Expressão Gênica , Humanos , Ácidos Hidroxieicosatetraenoicos/urina , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , VirulênciaRESUMO
This study investigated the effect of a single dose of tomato sauce on healthy male volunteers in a randomized crossover study. Healthy male subjects (n = 10) were enrolled. Placebo (rice and olive oil) or tomato (tomato sauce, rice and olive oil) meals were provided to the volunteers. Blood and urine samples were taken before consumption of meal (0 h) and 2, 4, 6, 24 and 48 h after meal. Consumption of tomato sauce increased plasma lycopene level by 5-22%, with a maximum level at 24 h (p<0.01) after the meal. Levels of plasma F(2)-isoprostanes, hydroxyeicosatetraenoic acid products, allantoin and urinary 8-hydroxy-2'-deoxyguanosine did not change after either meal, but urinary F(2)-isoprostanes (p<0.05) significantly decreased at 48 h compared to 0 h after the tomato sauce meal. This study showed that a single dose of tomato sauce meal had only a limited antioxidant effect in vivo.
Assuntos
Antioxidantes/administração & dosagem , Biomarcadores/análise , Carotenoides/sangue , Solanum lycopersicum , Adulto , Alantoína/sangue , Cromatografia Líquida de Alta Pressão , Estudos Cross-Over , Desoxiadenosinas/urina , Dieta , F2-Isoprostanos/sangue , F2-Isoprostanos/urina , Humanos , Ácidos Hidroxieicosatetraenoicos/sangue , Licopeno , MasculinoRESUMO
Many products of lipid oxidation have been associated with human diseases. These include F2-isoprostanes (F2-IsoPs), hydroxyeicosatetraenoic acid products (HETEs), and cholesterol oxidation products (COPs). Here we present measurements of F2-IsoPs, HETEs, COPs, and arachidonate in single plasma samples of patients with acute (dengue fever and ischemic stroke) and chronic (Parkinson's) diseases, and in age-matched study controls. Urine samples were collected for F2-IsoPs analysis. Our analysis demonstrated elevated F2-IsoPs levels in ischemic stroke, HETEs in Parkinson's disease, dengue fever, and ischemic stroke, and COPs in Parkinson's disease and dengue fever patients, as compared with those in age-matched study controls. Strong but complex correlations were observed between levels of certain oxidized lipid products and age. The relations between various oxidized lipids and dengue fever, stroke, and Parkinson's disease are discussed in relation to the selection and application of biomarkers of oxidative lipid damage, in particular the need for corrections for age and lipid levels.
Assuntos
Biomarcadores/metabolismo , Dengue/metabolismo , Metabolismo dos Lipídeos , Estresse Oxidativo , Doença de Parkinson/metabolismo , Acidente Vascular Cerebral/metabolismo , Biomarcadores/sangue , Biomarcadores/urina , Dengue/sangue , Dengue/urina , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Oxirredução , Doença de Parkinson/sangue , Doença de Parkinson/urina , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/urinaRESUMO
Vitamin C is a potent antioxidant in vitro and has been reported to act as a vasodilator, possibly by increasing nitric oxide bioavailability. This study examined the antioxidant and vascular effects of a single large oral dose of vitamin C in 26 healthy human volunteers. Haemodynamic and oxidative DNA and lipid damage markers were measured for 8 h following an oral dose of 2 g vitamin C or placebo. Vitamin C had no effect on vasodilation (measured by augmentation index (mean change=0.04%, 90% CI=- 2.20% to 2.28%) or forearm blood flow (-0.19%/min (-0.68, 0.30)), in comparison to placebo) or on several markers of oxidative stress including DNA base oxidation products in blood cells, 8-hydroxy-2'-deoxyguanosine (8O HdG) in urine (0.068 (-0.009, 0.144)) or urinary or plasma total F(2)-isoprostanes (-0.005 ng/ml (-0.021, 0.010), -0.153 ng/mg (-0.319, 0.014), respectively).
Assuntos
Artérias/efeitos dos fármacos , Ácido Ascórbico/farmacologia , Pressão Sanguínea , Estresse Oxidativo , Administração Oral , Adulto , Antioxidantes/metabolismo , Ácido Ascórbico/metabolismo , Biomarcadores/metabolismo , Feminino , Hemodinâmica , Humanos , Lipídeos/química , Masculino , Placebos , Vasodilatadores/farmacologiaRESUMO
Oxidized lipids such as F2-isoprostanes (F2-IsoPs), hydroxyeicosatetraenoic acid products (HETEs), and cholesterol oxidation products (COPs) are widely believed to be involved in multiple diseases. Usually, each product is measured individually in separate blood samples. In this study we describe a method allowing us to measure F2-IsoPs, HETEs, COPs, and arachidonate using a single sample. Plasma (1 ml) samples from healthy volunteers were diluted with heavy isotopic standards, hydrolyzed in alkali with organic solvent, and then subjected to anionic-exchange solid-phase extraction (SPE). After the SPE column was washed, hexane and hexane/ethyl acetate portions were collected and combined for COPs measurement. Thereafter the column was loaded with hexane/ethanol/acetic acid and fractions were collected for total F2-IsoPs, total HETEs, and arachidonate measurement. All compounds in the eluates were measured by gas chromatography-mass spectrometry. The efficiency of SPE and reproducibility for all compounds measured were high. Levels of total F2-IsoPs (0.45+/-0.26 ng/ml (n=157)), total HETEs (34.06+/-16.35 ng/ml (n=21)), total arachidonate (68.36+/-24.45 microg/ml (n=33)), and COPs (7-ketocholesterol, 12.25+/-6.56 ng/ml; 7beta-hydroxycholesterol, 6.32+/-3.46 ng/ml; 7alpha-hydroxycholesterol, 15.06+/-7.06 ng/ml; 24-hydroxycholesterol, 41.39+/-18.22 ng/ml; and 27-hydroxycholesterol, 29.08+/-16.79 ng/ml (n=26)) were recorded in healthy subjects (age range 20 to 66 years; average male to female ratio 1:1).
Assuntos
F2-Isoprostanos/metabolismo , Ácidos Hidroxieicosatetraenoicos/química , Esteróis/metabolismo , Acetatos/química , Adulto , Idoso , Ácido Araquidônico/química , F2-Isoprostanos/análise , Feminino , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Ácidos Hidroxieicosatetraenoicos/análise , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Reprodutibilidade dos Testes , Solventes/química , Esteróis/análiseRESUMO
Hydrogen sulfide (H(2)S) is a gasotransmitter that regulates cardiovascular functions. The present study aimed to examine the hypothesis that chronic treatment with sodium hydrosulfide (NaHS, an H(2)S donor) is able to prevent left-ventricular remodeling in spontaneously hypertensive rats (SHR). Four-week-old SHR were treated with NaHS (10, 30, and 90 micromol x kg(-1) x day(-1)), a combination of NaHS (30 micromol x kg(-1) x day(-1)) and glibenclamide (5 mg x kg(-1) x day(-1)), glibenclamide alone (5 mg x kg(-1) x day(-1)), hydralazine alone (10 mg x kg(-1) x day(-1)), and placebo for 3 mo. At the end of the treatment period, variables such as cardiac geometry and function, intramyocardial arterioles ranging in diameter from 25 to 100 microm, perivascular and interstitial collagen content, reactive oxygen species (ROS), thiol groups, conjugated dienes, and DNA base modification were examined. The novel finding of the present study is that chronic NaHS treatment prevented the hypertrophy of intramyocardial arterioles and ventricular fibrosis, as well as decreased myocardial ROS and conjugated diene levels. The cardioprotective effects were blunted by coadministration of glibenclamide, suggesting a role of ATP-sensitive potassium channels in mediating the action of NaHS. Hydralazine caused a comparable reduction of blood pressure compared with NaHS treatment; however, it exerted no effect on the remodeling process or on ROS and conjugated diene levels. Moreover, NaHS treatment caused an increase in myocardial thiol group levels, whereas DNA base modification was not altered by NaHS treatment. In conclusion, the superior cardioprotective effects of NaHS treatment are worthy to be further explored to develop novel therapeutic approaches for the treatment of cardiac remodeling in hypertension.
Assuntos
Anti-Hipertensivos/farmacologia , Cardiotônicos/farmacologia , Vasos Coronários/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Miocárdio/patologia , Espécies Reativas de Oxigênio/metabolismo , Sulfetos/farmacologia , Disfunção Ventricular Esquerda/prevenção & controle , Remodelação Ventricular/efeitos dos fármacos , Animais , Anti-Hipertensivos/uso terapêutico , Análise Química do Sangue , Pressão Sanguínea/efeitos dos fármacos , Cardiomegalia/etiologia , Cardiomegalia/metabolismo , Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Cardiomegalia/prevenção & controle , Cardiotônicos/uso terapêutico , Colágeno/metabolismo , Vasos Coronários/metabolismo , Vasos Coronários/patologia , DNA/efeitos dos fármacos , DNA/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Fibrose , Glibureto/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Hidralazina/farmacologia , Hipertensão/complicações , Hipertensão/metabolismo , Hipertensão/patologia , Hipertensão/fisiopatologia , Masculino , Miocárdio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Compostos de Sulfidrila/metabolismo , Sulfetos/uso terapêutico , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/metabolismo , Disfunção Ventricular Esquerda/patologia , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
The role of hydrogen sulfide (H(2)S) in myocardial infarction (MI) has not been previously studied. We therefore investigated the effect of H(2)S in a rat model of MI in vivo. Animals were randomly divided into three groups (n = 80) and received either vehicle, 14 micromol/kg of sodium hydrosulfide (NaHS), or 50 mg/kg propargylglycine (PAG) everyday for 1 wk before surgery, and the treatment was continued for a further 2 days after MI when the animals were killed. The mortality was 35% in vehicle-treated, 40% in PAG-treated, and 27.5% in NaHS-treated (P < 0.05 vs. vehicle) groups. Infarct size was 52.9 +/- 3.5% in vehicle-treated, 62.9 +/- 7.6% in PAG-treated, and 43.4 +/- 2.8% in NaHS-treated (P < 0.05 vs. vehicle) groups. Plasma H(2)S concentration was significantly increased after MI (59.2 +/- 7.16 microM) compared with the baseline concentration (i.e., 38.2 +/- 2.07 microM before MI; P < 0.05). Elevated plasma H(2)S after MI was abolished by treatment of animals with PAG (39.2 +/- 5.02 microM). We further showed for the first time cystathionine-gamma-lyase protein localization in the myocardium of the infarct area by using immunohistochemical staining. In the hypoxic vascular smooth muscle cells, we found that cell death was increased under the stimuli of hypoxia but that the increased cell death was attenuated by the pretreatment of NaHS (71 +/- 1.2% cell viability in hypoxic vehicle vs. 95 +/- 2.3% in nonhypoxic control; P < 0.05). In conclusion, endogenous H(2)S was cardioprotective in the rat model of MI. PAG reduced endogenous H(2)S production after MI by inhibiting cystathionine-gamma-lyase. The results suggest that H(2)S might provide a novel approach to the treatment of MI.
Assuntos
Sulfeto de Hidrogênio/metabolismo , Infarto do Miocárdio/metabolismo , Isquemia Miocárdica/metabolismo , Alcinos/farmacologia , Animais , Morte Celular/efeitos dos fármacos , Células Cultivadas , Meios de Cultura/análise , Cistationina gama-Liase/antagonistas & inibidores , Cistationina gama-Liase/metabolismo , Modelos Animais de Doenças , Inibidores Enzimáticos/farmacologia , Glicina/análogos & derivados , Glicina/farmacologia , Sulfeto de Hidrogênio/análise , Masculino , Infarto do Miocárdio/patologia , Infarto do Miocárdio/prevenção & controle , Isquemia Miocárdica/patologia , Isquemia Miocárdica/prevenção & controle , Miocárdio/metabolismo , Miocárdio/patologia , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Sulfetos/farmacologiaRESUMO
Apoptosis has been well documented to play a significant role in cell loss during neurodegenerative disorders, such as stroke, Parkinson disease, and Alzheimer's disease. In addition, reactive oxygen species (ROS) has been implicated in the cellular damage during these neurodegenerative disorders. These ROS can react with cellular macromolecular through oxidation and cause the cells undergo necrosis or apoptosis. The control of the redox environment of the cell provides addition regulation in the signal transduction pathways which are redox sensitive. Recently, many researches focus on the relationship between apoptosis and oxidative stress. However, till now, there is no clear and defined mechanisms that how oxidative stress could contribute to the apoptosis. This review hopes to make clear that generation of ROS during brain injury, particularly in ischemic stroke and Alzheimer's Disease, and the fact that oxidative state plays a key role in the regulation and control of the cell survival and cell death through its interaction with cellular macromolecules and signal transduction pathway, and ultimately helps in developing an unique therapy for the treatment of these neurodegenerative disorders.
Assuntos
Apoptose/fisiologia , Encéfalo/metabolismo , Doenças Neurodegenerativas/metabolismo , Neurônios/metabolismo , Estresse Oxidativo/fisiologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Animais , Encéfalo/patologia , Encéfalo/fisiopatologia , Isquemia Encefálica/metabolismo , Isquemia Encefálica/fisiopatologia , Humanos , Doenças Neurodegenerativas/genética , Doenças Neurodegenerativas/fisiopatologia , Neurônios/patologia , Oxirredução , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/fisiologiaRESUMO
The purpose of the current study is to evaluate the cardioprotective effects of purified Salvia miltiorrhiza extract (PSME) on myocardial ischemia/reperfusion injury in isolated rat hearts. Hearts were excised and perfused at constant flow (7 - 9 ml.min(-1)) via the aorta. Non-recirculating perfusion with Krebs-Henseleit (KH) solution was maintained at 37 degrees C and continuously gassed with 95% O2 and 5% CO2. KH solution with or without PSME (100 mg per liter solution) was used after 30-min zero-flow ischemia for the PSME and control group, respectively. Left ventricular (LV) developed pressure; its derivatives, diastolic pressure, and so on were continuously recorded via a pressure transducer attached to a polyvinylchloride balloon that was placed in the left ventricle through an incision in the left atrium. PSME treated hearts showed significant postischemic contractile function recovery (developed pressure recovered to 44.2 +/- 4.9% versus 17.1 +/- 5.7%, P<0.05; maximum contraction recovered to 57.2 +/- 5.9% versus 15.1 +/- 6.3%, P<0.001; maximum relaxation restored to 69.3 +/- 7.3% versus 15.4 +/- 6.3%, P<0.001 in the PSME and control group, respectively). Significant elevation in end-diastolic pressure, which indicated LV stiffening in PSME hearts might have resulted from the excess high dose of PSME used. Further study will be conducted on the potential therapeutic value with lower dose of PSME on prevention of ischemic heart disease.
Assuntos
Cardiotônicos/farmacologia , Coração/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Extratos Vegetais/farmacologia , Salvia miltiorrhiza , Animais , Técnicas In Vitro , Masculino , Contração Miocárdica , Isquemia Miocárdica/fisiopatologia , Perfusão , Ratos , Ratos Wistar , Função Ventricular EsquerdaRESUMO
Attack on DNA by some reactive nitrogen species results in deamination of adenine and guanine, leading to the formation of hypoxanthine and xanthine, respectively. Published levels of these products in cellular DNA have varied widely. Although these two deamination products are often measured by GC-MS analysis, the procedure of acid hydrolysis to release DNA bases for derivatization poses a risk of artifactual deamination of the DNA. In this study, we demonstrated the artifactual formation of these two deamination products during acid hydrolysis and hence developed a method for detecting and measuring 2'-deoxyinosine, the nucleoside of hypoxanthine. Our assay for 2'-deoxyinosine employs nuclease P1 and alkaline phosphatase to achieve release of the nucleosides from DNA, followed by HPLC prepurification with subsequent GC-MS analysis of the nucleosides. This assay detected an increase in the levels of 2'-deoxyinosine in DNA when commercial salmon testis DNA was treated with nitrous acid. We also used it to measure levels in various rat tissues of both normal and endotoxin-treated rats, but could not find increased 2'-deoxyinosine formation in tissues even though *NO production was substantially increased.
Assuntos
Artefatos , DNA/metabolismo , Aminação , Animais , Bovinos , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Hidrólise , Hipoxantina/metabolismo , Células Jurkat , Lipopolissacarídeos/farmacologia , Óxido Nítrico/biossíntese , Estresse Oxidativo , Ratos , Sepse/metabolismo , Xantina/metabolismoRESUMO
Dark soy sauce (DSS) is a powerful antioxidant in vitro. We investigated whether this effect could occur in vivo and improve vascular function. Healthy human subjects were given DSS or placebo meals in a randomized, crossover study. Blood and urine were sampled before and 1, 2, 3, and 4h after the meal for F(2)-isoprostanes (total, free, and esterified) and 8OHdG measurements. Blood pressure, vascular augmentation index (AIx), and heart rate (HR) were also measured. Plasma total F(2)-isoprostanes significantly decreased 3h after placebo and the decrease was greater for DSS. Plasma free and esterified F(2)-isoprostanes were also significantly decreased after DSS. Both placebo and DSS meals increased urinary F(2)-isoprostanes at 1h but not thereafter, and lowered urinary 8OHdG levels, DBP and AIx, and increased HR. We conclude that DSS decreases lipid peroxidation in vivo. However, oxidative damage biomarkers changed after the placebo meal, a phenomenon to consider when designing interventional studies.
Assuntos
Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/metabolismo , Desoxiguanosina/análogos & derivados , F2-Isoprostanos/análise , Estresse Oxidativo/fisiologia , Extratos Vegetais/administração & dosagem , Alimentos de Soja , 8-Hidroxi-2'-Desoxiguanosina , Antioxidantes/administração & dosagem , Biomarcadores/sangue , Biomarcadores/urina , Estudos Cross-Over , Desoxiguanosina/análise , Humanos , Estresse Oxidativo/efeitos dos fármacosRESUMO
We aimed to determine whether nitroparacetamol (NO-paracetamol) and paracetamol exhibit cardioprotective effects. Myocardial infarction (MI) was induced in rats, and drug treatment was started 1 wk before surgery. Mortality rate and infarct size at 2 days after MI were compared. Treatment groups included vehicle (saline), paracetamol (5 mg x kg(-1) x day(-1)) and NO-paracetamol (15 mg x kg(-1) x day(-1)). Mortality rates for vehicle (n = 80), paracetamol (n = 79), and NO-paracetamol (n = 76) groups were 37.5%, 21.5%, and 26.3%, respectively. Infarct size for the vehicle group was 44.8% (+/-6.1%) of the left ventricle (LV). For the paracetamol and NO-paracetamol groups, infarct size was 31.3% (+/-5.6%) and 30.7% (+/-8.1%) of the LV, respectively. Both paracetamol- and NO-paracetamol-treated groups showed increased activities of catalase and SOD compared with the vehicle group. They could attenuate endothelial, inducible, and neuronal nitric oxide synthase and cyclooxygenase-1 and -2 gene expression after MI. The observation indicates the potential clinical significance of the cardioprotective effects of these drugs.
Assuntos
Acetaminofen/análogos & derivados , Acetaminofen/farmacologia , Cardiotônicos/farmacologia , Infarto do Miocárdio/fisiopatologia , Nitratos/farmacologia , Animais , Capilares/patologia , Vasos Coronários/patologia , Hemodinâmica/efeitos dos fármacos , Fígado/enzimologia , Masculino , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/patologia , Nitratos/sangue , Óxido Nítrico Sintase/genética , Nitritos/sangue , Oxirredutases/metabolismo , Prostaglandina-Endoperóxido Sintases/genética , RNA Mensageiro/metabolismo , Ratos , Ratos WistarRESUMO
In the current study, we compared purified Salvia miltiorrhiza extract (PSME) with Angiotensin-converting enzyme inhibitor, Ramipril, in in vitro experiments and also in vivo using animal model of myocardial infarction. PSME was found to have a significantly higher trolox equivalent antioxidant capacity which indicated a great capacity for scavenging free radicals. PSME could also prevent pyrogallo red bleaching and DNA damage. After 2 weeks treatment with PSME or Ramipril, survival rates of rats with experimental myocardial infarction were marginally increased (68.2% and 71.4%) compared with saline (61.5%). The ratios of infarct size to left ventricular size in both PSME-and Ramipril-treated rats were significantly less than that in the saline-treated group. Activity of cardiac antioxidant enzyme superoxide dismutase (SOD) was significant higher while level of Thiobarbituric acid-reactive substances (TBARs) was lower in the PSME treated group. Purified and standardized Chinese herb could provide an alternative regimen for the prevention of ischemic heart disease.
Assuntos
Antioxidantes/uso terapêutico , Infarto do Miocárdio/complicações , Isquemia Miocárdica/tratamento farmacológico , Fitoterapia , Pirogalol/análogos & derivados , Salvia miltiorrhiza/química , Análise de Variância , Animais , Benzotiazóis , Dano ao DNA/efeitos dos fármacos , Medicamentos de Ervas Chinesas/uso terapêutico , Cromatografia Gasosa-Espectrometria de Massas , Masculino , Isquemia Miocárdica/etiologia , Ramipril/uso terapêutico , Ratos , Ratos Wistar , Espectrofotometria , Ácidos Sulfônicos , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Remodelação Ventricular/efeitos dos fármacosRESUMO
Our current study was to test the hypothesis that the extract of Herba leonuri (HL) would have antioxidant and cardioprotective effects on ischemic myocardium. The extract of HL (400 mg/kg/day) was administered orally (daily) starting from 1 week before and continuing until 3 weeks after myocardial infarction (MI). Surviving rats were sacrificed at different time points to obtain left ventricles for biochemical assays. Our study demonstrates for the first time that HL does have antioxidant effects both in vitro and in vivo. The antioxidant effects of HL are exerted only under the condition of oxidative stress, by selectively preserving the activities of superoxide dismutase and glutathione peroxidase, as well as depressing the formation of malondialdehyde, especially in the acute phase of acute MI. Its effects of scavenging free radicals and inhibiting the formation of reactive oxygen species may play a key role in protecting the endogenous antioxidant system from oxidative stress in vivo.