RESUMO
BACKGROUND: The current research on Alzheimer's disease is mainly focused in the post-mortem characterization of pathological and biochemical alterations in the brain. The finding of peripheral markers that could be associated with the changes observed in the Alzheimer's brain would be of interest in this field. The aim of the present study was to evaluate the state of different peripheral markers of oxidative stress in probable Alzheimer patients and compare them with a group of healthy individuals. DESIGN: The determinations made include the plasma total antioxidant capacity (TRAP) and tert-butyl hydroperoxide-initiated chemiluminescence and catalase activity in erythrocytes from 18 patients with probable Alzheimer's disease and 18 matched control subjects with normal cognitive function. RESULTS: TRAP was decreased in Alzheimer patients by 24% (control group 308 micromol L-1 Trolox, SEM 34, n = 18). tert-Butyl hydroperoxide-initiated chemiluminescence and catalase activity showed an increase in erythrocytes from Alzheimer patients by 52% (control group 116 700 cps mg-1 haemoglobin, SEM 6690) and 75% (control group 2.55 pmol mg-1 protein, SEM 0.39, n = 18) respectively. CONCLUSION: Oxidative stress in the blood of probable Alzheimer patients could be a reflection of the brain condition and suggests that oxygen free radicals could be partially responsible of the damage observed in this disease.
Assuntos
Doença de Alzheimer/sangue , Antioxidantes/análise , Catalase/sangue , Eritrócitos/fisiologia , Estresse Oxidativo , Idoso , Doença de Alzheimer/psicologia , Antioxidantes/metabolismo , Biomarcadores/sangue , Eritrócitos/efeitos dos fármacos , Feminino , Hemoglobinas/análise , Humanos , Medições Luminescentes , Masculino , Valores de Referência , terc-Butil Hidroperóxido/farmacologiaRESUMO
The oxidative stress in human erythrocytes was studied in asymptomatic and symptomatic patients infected by the human immunodeficiency virus (HIV), and patients with the acquired immunodeficiency syndrome (AIDS). tert-Butyl hydroperoxide initiated chemiluminescence, superoxide dismutase and catalase activities, and total glutathione were evaluated in the erythrocytes and the total antioxidant capacity in the plasma of control, patients infected with HIV that have not yet developed acquired immunodeficiency syndrome, and patients in the later stage of AIDS. tert-Butyl hydroperoxide initiated chemiluminescence was increased by 33% in asymptomatic (stage A1) and symptomatic patients (stage B2) infected with HIV and 82% for patients with AIDS (stage B3) (P < 0.05). While catalase activity did not show any difference between patients and controls, other indices showed differences that, in some cases, reached statistical significance. Superoxide dismutase activity was increased by 24% in stages A1 and B2 of HIV infection and 65% in patients in stage B3 (P < 0.05). Glutathione was decreased by 20% in stages A1 and B2, and by 32% in stage B3 patients (P < 0.05). Total plasma antioxidant capacity was increased in 30 and 57% for the asymptomatic and AIDS patients groups, respectively (P < 0.05). The data indicate that erythrocyte's oxidative stress is associated with the progressive development of HIV disease. Parameters indicating oxidative stress could be an interesting form to screen the evolution of these patients and their response to anti-oxidant therapies.
Assuntos
Eritrócitos/metabolismo , Infecções por HIV/metabolismo , Estresse Oxidativo/fisiologia , Adulto , Antioxidantes/metabolismo , Catalase/sangue , Catalase/metabolismo , Feminino , Radicais Livres/metabolismo , Glutationa/sangue , Glutationa/metabolismo , Humanos , Medições Luminescentes , Masculino , Peróxidos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/sangue , Superóxido Dismutase/metabolismo , terc-Butil HidroperóxidoRESUMO
A study of several elements of the antioxidative system: Cu-Zn superoxide dismutase (SOD), catalase (CAT), glutathione system (GLU), chemiluminescence (CHE), and antioxidant capacity (AOX), was conducted in 20 demented probable Alzheimer's (DAT), and 15 vascular demented (VD) patients, 19 control (C) subjects, and 11 relatives (F) of one DAT patient. A significant association was found between the variables of the antioxidant system, measured in blood samples, and the neurological pathologies VD and DAT: Kruskal-Wallis test; p = 0.0006 (p = 0.014 when the analysis did not include SOD). This demonstrated that VD and DAT diseases are accompanied by oxidative disorders. The VD and DAT diseases are differentially distinguishable by changes in blood profiles. A graphical method for classification, the Principal Components Analysis (PCA), distinguished between demented and non-demented subjects on the basis of their laboratory variables. A numerical method, Discriminant Functions (DF), constructed to separate the clinical groups on the basis of the same variables, obtained relatively high percentages of success: 92% of demented were detected against healthy subjects; of the latter 82% have been correctly identified as non-demented. Discrimination between VD and DAT patients was achieved for 100% of VD and 86% of DAT patients. DF were similarly successful in detecting the healthy condition of DAT relatives. Possible different mechanisms involved in H2O2 elimination in DAT and VD patients are proposed, where CAT is the responsible enzyme of this reaction in DAT patients, while in VD this function would be achieved mainly through the action of GLU. It seems that SOD levels are stable, at least, within one year. Variations appear to be linked with clinical changes.
Assuntos
Doença de Alzheimer/sangue , Doença de Alzheimer/enzimologia , Antioxidantes/metabolismo , Doenças Vasculares/sangue , Doenças Vasculares/enzimologia , Idoso , Doença de Alzheimer/diagnóstico , Biomarcadores , Catalase/sangue , Interpretação Estatística de Dados , Diagnóstico Diferencial , Eritrócitos/enzimologia , Saúde da Família , Radicais Livres , Glutationa/metabolismo , Humanos , Medições Luminescentes , Estresse Oxidativo/fisiologia , Superóxido Dismutase/sangue , Doenças Vasculares/diagnósticoRESUMO
We studied nitrogen radical nitric oxide (.NO) release and reactive oxygen species (ROS) production by isolated neutrophils after phorbol myristate acetate (PMA) stimulation in 12 newly diagnosed and nine treated Parkinson's disease (PD) patients and 10 age-matched healthy controls. Neutrophils of both groups of PD patients had an elevated PMA-activated release of .NO [61 and 57%, respectively, higher than that of controls (p < 0.05)]. In contrast, H2O2 release was only significantly increased by 56% in chronically treated patients. In agreement, the maximum rate of luminol-dependent chemiluminescence, which partly represents O2- H2O2- .NO interactions, was increased only in the treated group. When other blood markers of oxidative stress were compared, only erythrocyte catalase activity was decreased in both PD patient series by 33 and 39%, respectively (p < 0.05), whereas plasma antioxidant capacity and erythrocyte superoxide dismutase activity levels were decreased only in treated PD patients. This study suggests that neutrophils express a primary alteration of .NO release in PD patients, whereas H2O2 and oxidative-stress parameters are more probably related to the evolution of PD or to effects of treatment with L-dopa.
Assuntos
Neutrófilos/fisiologia , Óxido Nítrico/fisiologia , Estresse Oxidativo , Doença de Parkinson/fisiopatologia , Espécies Reativas de Oxigênio/metabolismo , Antiparkinsonianos/administração & dosagem , Carbidopa/administração & dosagem , Catalase/sangue , Quimioterapia Combinada , Eritrócitos/enzimologia , Feminino , Radicais Livres , Humanos , Peróxido de Hidrogênio/sangue , Levodopa/administração & dosagem , Medições Luminescentes , Masculino , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , Superóxido Dismutase/sangueRESUMO
CONCLUSION: Production of excited oxygen species is earlier in the liver than in the pancreas and could contribute to damage in a reflux model. Treatment with SOD could attenuate 59% light emission in pancreas, but did not modify serum enzyme levels or pancreatic edema, resulting as an insufficient isolated therapy. Unexpectedly, it was found an increased plasma antioxidant capacity that was related to total bilirubin levels, and declined at late stages probably denoting other circulating antioxidant consumption. BACKGROUND: Oxidative stress has been shown to play a role in different models of acute pancreatitis, although it has not been studied in the severe necrohemorrhagic model produced by closed duodenal loop pancreatitis. METHODS: We studied Sprague Dawley female rats in two groups: a closed duodenal loop pancreatitis group and a control, sham-operated group. In order to evidence the oxygen excited species production, in situ spontaneous chemiluminescence from living and naturally perfused pancreas and liver was measured at 0, 0.5, 1.5, 3, 6, 12, and 24 h after the duodenal ligature. Blood pancreatic amylase and aminotransferases levels were determined as expression of tissue damage in pancreas and liver. At the same time, plasma antioxidant capacity was measured by the peroxyl radical trapping capability of plasma samples compared to that of Trolox (synthetic analog of vitamin E), and results are expressed as Trolox equivalence. Bovine superoxide dismutase (SOD) was administered to attenuate oxygen free radicals activity at the beginning of the peroxidation chain and also as a therapeutic tool. RESULTS: The experimental procedure induced a severe pancreatitis, as evidenced by pancreatic enzymes that rose markedly in the early hours of disease and remained heightened throughout the experiment. The results show early light emission from the liver at 3 h and peak levels at 12 h, whereas in the pancreas, luminescence increased at 6 h and doubled later at 12 h, both returning to control levels at 24 h.
Assuntos
Estresse Oxidativo/fisiologia , Pancreatite/fisiopatologia , Doença Aguda , Alanina Transaminase/sangue , Amilases/sangue , Animais , Antioxidantes/farmacocinética , Cromanos/farmacocinética , Feminino , Medições Luminescentes , Neutrófilos/metabolismo , Pancreatite/sangue , Pancreatite/tratamento farmacológico , Ratos , Superóxido Dismutase/uso terapêutico , Superóxidos/metabolismoRESUMO
In this article the spontaneous chemiluminescence and the steady-state concentration of hydrogen peroxide were determined in rat liver as indicators of oxidative stress in the tissue. Hydroperoxide-initiated chemiluminescence and the activity of antioxidant enzymes (catalase, superoxide dismutase and glutathione peroxidase) were also measured to evaluate antioxidant defenses and serum activity of lactate dehydrogenase and aspartate aminotransferase. Mitochondrial morphology and mitochondrial respiratory control ratio were measured as indicators of cell and mitochondrial damage. Xanthine dehydrogenase and xanthine oxidase activities were determined as a possible source of oxyradicals. No significant changes were observed after 10 or 30 min of vena cava occlusion in any of the measured parameters. In contrast, 10 min of occlusion followed by 10 min of reperfusion increased chemiluminescence (from 18 +/- 3 to 32 +/- 5 cps/cm2), hydrogen peroxide (from 0.10 +/- 0.01 to 0.17 +/- 0.01 mumol/L), lactate dehydrogenase (from 80 +/- 2 to 330 +/- 30 U/L), and aspartate aminotransferase (from 42 +/- 2 to 100 +/- 10 U/L). Liver reperfusion was also associated with mitochondrial swelling and decreased mitochondrial respiratory control (from 5.6 +/- 0.3 to 2.6 +/- 0.1). The activity of the antioxidant enzymes and xanthine oxidase was instead without change. After 30 min of vena cava occlusion and 10 min of reperfusion a more marked increase in chemiluminescence (37 +/- 5 cps/cm2), hydrogen peroxide (0.30 +/- 0.01 mumol/L), lactate dehydrogenase (730 +/- 10 U/L) and aspartate aminotransferase (140 +/- 10 U/L) was observed. No further changes were found in either mitochondrial morphology or respiratory control (2.4 +/- 0.1) in isolated mitochondria.(ABSTRACT TRUNCATED AT 250 WORDS)