RESUMO
The objectives of this study were (1) to evaluate the capacity of human plasma that had been obtained from healthy adult volunteers before and after they ingested vitamin E or C to inhibit induced lipoperoxidation in vitro (antioxidant capacity of plasma [ACP]), and (2) to compare the efficiency of these vitamins with that of a commercial mixture of antioxidant vitamins, cofactors, and minerals (MAOx). Seventy-nine healthy individuals between 19 and 23 y of age were randomly assigned to 1 of 4 groups. Each received a daily dose of antioxidants for 7 d: vitamin C (n=18; 500 mg), vitamin E (n=21; 400 IU), vitamins C and E (n=19), or MAOx (n=21; 1.2 g). ACP and plasma malondialdehyde were measured at 4 and 24 h and 7 d. ACP increased significantly (P<.05) in all 4 groups within 4 h of antioxidant intake, and this effect was sustained throughout supplementation. Plasma ACP increased significantly over basal values in the group taking MAOx; relative increases were 42%, 44%, and 55% at 4 h, 24 h, and 7 d, respectively (P<.001). Smaller increases in plasma ACP were observed in the vitamin C group (25%, 32%, and 36%) and, specifically, in the vitamin E group (17%, 24%, and 28%) (P<.05). The mixture of vitamins and minerals was comparatively more efficient than vitamin C or E alone, presumably because MAOx contains various antioxidant compounds with different redox potentials, leading to the possible development of chain reactions.
Assuntos
Antioxidantes/metabolismo , Antioxidantes/uso terapêutico , Ácido Ascórbico/uso terapêutico , Vitamina E/uso terapêutico , Vitaminas/uso terapêutico , Administração Oral , Adulto , Antioxidantes/administração & dosagem , Ácido Ascórbico/administração & dosagem , Feminino , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Vitamina E/administração & dosagem , Vitaminas/administração & dosagemAssuntos
Antioxidantes/uso terapêutico , Suplementos Nutricionais , Recém-Nascido de muito Baixo Peso , Retinopatia da Prematuridade/prevenção & controle , Vitamina E/uso terapêutico , Administração Oral , Antioxidantes/administração & dosagem , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Recém-Nascido , Masculino , Estresse Oxidativo , Soluções , Vitamina E/administração & dosagemRESUMO
Peroxynitrite, the product of the reaction between *NO and O2*-, is a strong oxidant and nitrating molecule, and it has been recently consideredas a component of some important signaling pathways. Herein, we report the effect of peroxynitrite on glucose uptake in 3T3-L1 adipocytes. Peroxynitrite stimulated glucose uptake and this effect was inhibited by citochalasin B, indicating the participation of facilitated GLUT transporters. Peroxynitrite-induced glucose uptake was not related to intracellular ATP, nor to external or internal calcium, but it was inhibited by the phosphatidylinositol 3-kinase (PI3-K) inhibitor, wortmannin. Additionally, we also found that peroxynitrite did not activate the insulin receptor nor the PI3-K downstream signaling protein kinase B (PKB/Akt). The dose-dependent inhibitory action of wortmannin suggests that peroxynitrite activates glucose transport without affecting GLUT transporters translocation.
Assuntos
Adipócitos/enzimologia , Glucose/farmacocinética , Ácido Peroxinitroso/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Células 3T3-L1 , Trifosfato de Adenosina/metabolismo , Androstadienos/farmacologia , Animais , Cálcio/metabolismo , Sobrevivência Celular , Citocalasina B/farmacologia , Relação Dose-Resposta a Droga , Glucose/metabolismo , Camundongos , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , WortmaninaRESUMO
[This corrects the article DOI: 10.1111/j.1752-8062.2012.00391.x.].
RESUMO
Pebisut is a biological adhesive composed of naturally occurring carbohydrates combined with zinc oxide (ZnO) initially used as a coadjutant for healing of anastomoses. Likewise some works demonstrated that carbohydrate complexes exerts anti-inflammatory activity and it is widely known that ZnO modulate inflammation. However, the direct effects of Pebisut on isolated cells and acute inflammatory responses remained to be investigated. The present study evaluated anti-inflammatory effect of Pebisut using lipopolysaccharide (LPS) stimulated human mononuclear cells, chemotaxis, and cell infiltration in vivo in a murine model of peritonitis. Our data show that human cells treated with different dilutions of Pebisut release less IL-6, IL-1 ß , and IL-8 after LPS stimuli compared with the control treated cells. In addition, Pebisut lacked chemotactic activity in human mononuclear cells but was able to reduce chemotaxis towards CCL2, CCL5, and CXCL12 that are representative mononuclear cells chemoattractants. Finally, in a murine model of peritonitis, we found less number of macrophages (F4/80(+)) and T lymphocytes (CD3(+)) in peritoneal lavages from animals treated with Pebisut. Our results suggest that Pebisut has anti-inflammatory activity, which might have a beneficial effect during anastomoses healing or wounds associated with excessive inflammation.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Carboidratos/farmacologia , Peritonite/tratamento farmacológico , Óxido de Zinco/farmacologia , Animais , Quimiotaxia/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Lipopolissacarídeos/toxicidade , Macrófagos Peritoneais/metabolismo , Macrófagos Peritoneais/patologia , Masculino , Camundongos , Peritonite/induzido quimicamente , Peritonite/patologia , Linfócitos T/metabolismo , Linfócitos T/patologiaRESUMO
In a subanalysis on the metformin, arterial function, intima-media thickness, and nitroxidation in the metabolic syndrome (MEFISTO)(8) (an open-label fashion, with 1 year of 850 mg daily of metformin) subjects' samples, we measured the paraoxonase 1 (PON1) activity in 39 patients that finished the study and relate values with high density lipoprotein (HDL). The comparative PON1 activities at the beginning and at the end of the study were 5.528 ± 0.588 and 4.743 ± 0.619 nmol/mg protein/min (NS) for control group and 3.229 ± 0.403 and 5.135 ± 0.585 nmol/mg protein/min (p < 0.02) for the metformin group. Our data showed an enhance of PON1 activity in patients with metabolic syndrome treated with metformin, although in them, the raise of HDL concentration was less than control patients, suggesting that the increase in quality (measured here as PON1 activity) could be at least as important as an increase in its concentration. Our results point out that there is a relationship among PON1 activity and the reduction of carotideal intima-media thickness.
Assuntos
Arildialquilfosfatase/metabolismo , Hipoglicemiantes/uso terapêutico , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/enzimologia , Metformina/uso terapêutico , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Humanos , Lipoproteínas HDL/sangue , Síndrome Metabólica/sangueRESUMO
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an inflammatory disease that is characterized by a progressive and irreversible decline in lung function and is caused primarily by chronic exposure to tobacco and to wood smoke. It is linked to oxidative stress and to an up-regulation of airway arginases and is also associated with alterations in platelets and erythrocytes. In the present study, arginase activity was studied in platelets and erythrocytes of 2 groups of COPD patients: 31 tobacco ex-smokers and 27 patients who had been exposed to wood smoke. A total of 15 healthy controls were also included. METHODS: Plasma, platelets, and erythrocytes were obtained from the blood samples. Levels of the oxidative stress biomarkers, carbonyls and malondialdehyde, were measured in the plasma, and arginase activity was quantified in platelets and erythrocytes. RESULTS: In both groups of COPD patients, an increase in the oxidative stress biomarkers was found. Platelet arginase activity in both COPD groups was 2-fold higher than that in the control group. In the erythrocytes, the arginase activity increased 1.7-fold over the control only in the wood smoke-induced COPD group. DISCUSSION AND CONCLUSIONS: These results suggest that the increase in arginase activity in platelets and erythrocytes participates in the alteration in nitric oxide metabolism in COPD patients and that there may be some differences between the tobacco smoke- and wood smoke-induced COPD.
Assuntos
Arginase/metabolismo , Plaquetas/enzimologia , Eritrócitos/enzimologia , Doença Pulmonar Obstrutiva Crônica/enzimologia , Fumaça/efeitos adversos , Fumar/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Estudos de Casos e Controles , Ativação Enzimática/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Doença Pulmonar Obstrutiva Crônica/etiologia , Fumar/efeitos adversos , MadeiraRESUMO
Injury to red blood cell (RBC) membrane by oxidative stress is of clinical importance in chronic obstructive pulmonary disease (COPD) which leads to oxidative stress (OE) during disease progression. Here, we studied the impact of this stress on injury to RBC membrane. Blood samples from both healthy volunteers (HV, n = 11) and controlled COPD patients (n=43) were divided according to their GOLD disease stage (I=7, II=21, III=10, IV=5). Plasma levels of paraoxonase (PON) activity, protein carbonyls (PC), conjugate dienes, lipohydroperoxides (LPH) and malondialdehyde (MDA) were determined and the PTPase, and the oxidative parameters were measured in RBC ghosts. Plasma from patients with COPD showed an increased oxidation of lipids and proteins, that correlated with the disease progression. PON activity decreased from GOLD stages II to IV and correlated with an increase in LPH (p less than 0.0001, r = -0.8115). There was evidence of an increase in the oxidative biomarkers in RBCs, while the PTPase activity was diminished in stage III and IV of COPD. In conclusion, OE-induced injury associated with COPD is associated with an oxidative damage to the RBC membrane, with a concomitant decrease in the PTPase activity and altered function of anionic exchanger (AE1).
Assuntos
Proteína 1 de Troca de Ânion do Eritrócito/metabolismo , Biomarcadores/sangue , Membrana Eritrocítica/metabolismo , Proteínas Tirosina Fosfatases/metabolismo , Doença Pulmonar Obstrutiva Crônica/sangue , Progressão da Doença , Membrana Eritrocítica/enzimologia , Humanos , Doença Pulmonar Obstrutiva Crônica/patologiaRESUMO
BACKGROUND: The Mexico City Metropolitan Area is densely populated, and toxic air pollutants are generated and concentrated at a higher rate because of its geographic characteristics. It is well known that exposure to particulate matter, especially to fine and ultra-fine particles, enhances the risk of cardio-respiratory diseases, especially in populations susceptible to oxidative stress. The aim of this study was to evaluate the effect of fine particles on the respiratory burst of circulating neutrophils from asthmatic patients living in Mexico City. METHODS: In total, 6 subjects diagnosed with mild asthma and 11 healthy volunteers were asked to participate. Neutrophils were isolated from peripheral venous blood and incubated with fine particles, and the generation of reactive oxygen species was recorded by chemiluminescence. We also measured plasma lipoperoxidation susceptibility and plasma myeloperoxidase and paraoxonase activities by spectrophotometry. RESULTS: Asthmatic patients showed significantly lower plasma paraoxonase activity, higher susceptibility to plasma lipoperoxidation and an increase in myeloperoxidase activity that differed significantly from the control group. In the presence of fine particles, neutrophils from asthmatic patients showed an increased tendency to generate reactive oxygen species after stimulation with fine particles (PM2.5). CONCLUSION: These findings suggest that asthmatic patients have higher oxidation of plasmatic lipids due to reduced antioxidant defense. Furthermore, fine particles tended to increase the respiratory burst of blood human neutrophils from the asthmatic group.On the whole, increased myeloperoxidase activity and susceptibility to lipoperoxidation with a concomitant decrease in paraoxonase activity in asthmatic patients could favor lung infection and hence disrupt the control of asthmatic crises.
RESUMO
Lipid peroxidation induced by reactive oxygen species might modify circulating biomolecules because of the formation of alpha,beta-unsaturated or dicarbonylic aldehydes. In order to investigate the interaction between a lipoperoxidation product, acrolein, and a circulating protein, insulin, the acrolein-insulin adduct was obtained. To characterize the adduct, gel filtration chromatography, sodium dodecylsulfate-polyacrylamide gel electrophoresis and carbonyl determination were performed. Induction of hypoglycemia in the rat and stimulation of glucose uptake by 3T3 adipocytes were used to evaluate the biological efficiency of the adduct compared with that of native insulin (Mackness, B., Quarck, R., Verte, W., Mackness, M., and Holvoet, P. (2006) Arterioscler., Thromb. Vasc. Biol. 26, 1545-1550). Formation of the acrolein-insulin complex in vitro increased the carbonyl group concentration from 2.5 to 22.5 nmol/mg of protein, and it formed without intermolecular aggregates (Halliwell, B., and Whiteman, M. (2004) Br. J. Pharmacol. 142, 231-255. The hypoglycaemic effect 18 min after administration to the rat is decreased by 25% (Robertson, R. P. (2004) J. Biol. Chem. 279, 42351-42354. An adduct concentration of 94 nM, compared to 10 nM for native insulin, was required to obtain the A 50% (concentration needed to obtain 50% of maximum transport of glucose uptake by 3T3 adipocytes). In conclusion, formation of the acrolein-insulin adduct modifies the structure of insulin and decreases its hypoglycemic effect in rat and glucose uptake by 3T3 adipocytes. These results help explain how a toxic aldehyde prone to be produced in vivo can structurally modify insulin and change its biological action.
Assuntos
Acroleína/metabolismo , Adipócitos/metabolismo , Glucose/metabolismo , Hipoglicemiantes/metabolismo , Hipoglicemiantes/farmacologia , Insulina/metabolismo , Insulina/farmacologia , Células 3T3 , Adipócitos/efeitos dos fármacos , Animais , Hipoglicemiantes/química , Insulina/química , Peroxidação de Lipídeos , Masculino , Camundongos , Ratos , Ratos Sprague-DawleyRESUMO
La ovulación es un complejo proceso que además de gonadotropinas y esteroides requiere mediadores locales como las citocinas, que también participan en la respuesta inflamatorio. De interés particular es el sistema de la interleucina-1 (IL-1), que al parecer es un intermediario de las gonadotropinas en el proceso ovulatorio. El ovario cuenta con el sistema completo de IL-1 que incluye: ligandos, receptores y el antagonista del receptor. A la IL-1 se le atribuye la inducción de diversos eventos asociados con la ovulación como son: la producción de prostaglandinas, de progesterona, del activador del plasminógeno, glicosaminoglicanos y del aumento preovulatorio de la permeabilidad vascular. El principal efector de la interleucina-1 es el óxido nítrico. El interés de esta revisión es valorar la localización tisular y la acción de la IL-1 en el folículo preovulatorio y su dinámica vascular; así como analizar los mecanismos propuestos para la acción de la IL-1 como modulador de los eventos que llevan a la ruptura folicular.
Assuntos
Interleucina-1 , Ovulação/fisiologia , Óxido Nítrico/fisiologia , Fase Folicular , GonadotropinasRESUMO
La ingestión de etanol durante el embarazo ha sido considerada como una buen probada causa de efectos teratológicos en el embrión. El conjunto de alteraciones en el crecimiento y morfogénesis del producto son incluidas en el llamado síndrome de alcoholismo fetal (Fetal Alcohol Syndrome, FAS), caracterizado por deficiencia en el crecimiento, disfunción del SNC, anormalidades faciales y malformaciones de daño y las posibilidades de diagnóstico temprano son consideradas en la presente revisión.
Assuntos
Humanos , Gravidez , Feminino , Etanol/efeitos adversos , Transtornos do Espectro Alcoólico FetalRESUMO
La distribución de las poliaminas es universal y su concentración varía de un tejido otro. Su presencia está asociada con los procesos decrecimiento, multiplicación y diferenciación celulares normales. El metabolismo de estas moléculas se ha estudiado en el semen humano, testículos, epidídimo y próstata. Las poliaminas se han asociado con los procesos de capacitación espermática y fertilización. Algunos estudios de inhibición sugieren que las poliminas pueden estar involucradas en la regulación de procesos de posfertilización. Su detección oportuna en orina puede conducir al tratamiento de casos de prostatitis en una etapa curable
Assuntos
Humanos , Masculino , Poliaminas Biogênicas/fisiologia , Genitália Masculina/fisiologia , Reprodução/fisiologia , Prostatite/fisiopatologia , Sêmen/fisiologia , Espermatozoides/fisiologiaRESUMO
Twenty-one adult volunteers (aged 27-32 years), who had been living in Mexico City for four continuous months (physicians working as fellows) were studied the first and sixteenth week of their stay in order to learn the effect of the pollutants contained in Mexico City's atmosphere on some serum biochemical parameters. The activity of serum superoxide dismutase (SOD) decreased after 16 weeks in comparison with the values obtained the first week (109.6 to 56.9 mU/mg protein; 50 percent less). In contrast, the inhibitory capacity of serum vs. induced in vitro lipoperoxidation increased in relation to the length of stay (22 percent). The serum levels of thiobarbituric-reactive material also decreased in almost 30 percent (from 6.10 to 4.12 nmol). The other lipoperoxides measured were unchanged (chromolipids and diene conjugation). We propose that this may be as a result of the adaptive capacity of the human orgnaisms, within a pollutant atmosphere in which the ozone levels might participate in a decrease of SOD activity during chronic exposure, to air pollution
Assuntos
Humanos , Adulto , Poluentes Atmosféricos/farmacologia , Exposição Ambiental , Oxirredução , Ozônio/farmacologia , Peroxidação de Lipídeos , Superóxido Dismutase/sangue , MéxicoRESUMO
Hemos analizado las propiedades de los sitios de unión a 17-ß-esradiol, del tipo y libres y unidos del tipo II, en el citosol de endometrio de rata, en el día cinco de embarazo; las muestras corrsponden a endometrio receptivo al blastocisto (ER), endometrio no receptivo (ENR) y a endometrio de cuerno uterino ovariectomizado (EOv) de las mimas ratas embarazadas. El sitio de unión tipo II, ocupado por el esteroide, fue cuantificado por análisis de intercambio (incubado a 25-C durante 12 h). La constante de discociación obtenida al incubar a 4 o 25-C son semejantes para cad uno de los sitios de unión en las tres muestras de endodmetrio; la capacidad de unión (fentomoles/mg de proteínas) de los sitios de unión tipo I y tipo II y la relación entre sitios ocupados y no ocupados de tipo II por estadiol endógeno, parece ser característico para cada uno de los tres endometrios analizados
Assuntos
Ratos , Animais , Implantação do Embrião , Endométrio/fisiologia , Estradiol/fisiologia , Progesterona/fisiologia , Receptores de Estradiol/metabolismo , Receptores de Progesterona/metabolismo , Sítios de Ligação , MéxicoRESUMO
Se pensó por mucho tiempo que las citocinas sintetizadas por el útero y la placenta eran producidas exclusivamente por y para actuar sobre las células linfohematopoyéticas. Si bien muchas de estas citocinas modulan la fase efectora del sistema inmune, en el tracto reproductor femenino, sus principales células blanco y sitios de síntesis no son las células epiteliales uterinas, las células deciduales y el trofoblasto parecen ser la fuente principal de las citocinas. Esto sugiere dos alternativas no necesariamente exclusivas: o que estas células son extensiones que regulan al sistema inmune o que estos factores modulan el crecimiento y diferenciación de los tejidos uterinos y embrionarios. En el presente trabajo se analizan los sitios de síntesis, las células blanco y las posibles funciones de la citocinas durante la gestación temprana.
Assuntos
Blastocisto/fisiologia , Citocinas/fisiologia , Endométrio/fisiologia , Interleucinas/fisiologia , Gravidez/fisiologia , Trofoblastos/fisiologiaRESUMO
Recent studies have focused attention on the possible role of active oxygen species on protein damage and degradation. The reactions of free radicals on biomolecules are important in physiology and pathology. A number of systems that generate free radicals catalyze the oxidative modification of proteins in two species: protein peroxides, which can consume important antioxidants; and proteinbound reducing moieties, which can reduce transition metals, and may enhace their activity in radical reactions. Protein oxidation also contributes to the pool of damaged enzymes and accumulation of abnormal and damaged proteins, which increases during aging and in various pathological states, such as atherosclerosis, cancer, etc
Assuntos
Senescência Celular/fisiologia , Oxidação Química , Espécies Reativas de Oxigênio , Radicais Livres/efeitos adversos , Oxirredução , Proteínas/metabolismoRESUMO
Los lisosomas no deben considerarse sólo orgánulos que participan en la lisis de diferentes moléculas en proceso de digestión o defensa celular, ya que participan en diversos procesos de metabolismo celular, incluyendo los regulados hormonales. La actividad lisosomal se ve alterada minutos después de la administración de hormonas tanto esteroides como peptídicas incluyendo efectos como: labilización de membranas, cambio en la estructura química de las hidrolasas (latencia estructural) y migración perinuclear de lisosomas. Estas alteraciones demuestran que la actividad lisosomal es hormino-dependiente, y que hidrolasas como fosfatasa ácida pueden esta actuando de alguna manera a nivel de des-represión génica. Por otro lado, los lisosomas pueden propagar efectos hormonales desde la superficie de las células blanco hasta el núcleo. Es muy probable que ésta propagación se efectúe por medio de poblaciones especializadas de lisosomas que bajo el efecto hormonal migran a la región perinuclear. Se ha demostrado que ciertas substancias naturales y sintéticas que estabilizan membranas pueden bloquear esos eventos de distinto grado, de tal manera, que estos restablecen la labilización lisosomal y por consiguiente impiden la liberación enzimática. De una u otra forma, por lo anteriormente descrito, el sistema lisosomal participa en los mecanismos de comunicación autocrina, paracrina y endocrina
Assuntos
Camundongos , Coelhos , Ratos , Humanos , Animais , Feminino , Estrogênios/biossíntese , Técnicas In Vitro , Lisossomos/enzimologia , Lisossomos/metabolismo , Técnicas CitológicasRESUMO
Las hormonas esteroides son moléculares muy versátiles: a pesar de estar relacionada entre sí por su estructura química, cumplen funciones muy diversas, e incluso antagónicas. Su mecanismo de acción no esta aclarado totalmente. Los estrógenos participan en la regulación de prácticamente todos los eventos reproductivos y sexuales de la hembra, sin embargo, las acciones intracelulares por las que se llevan a cabo no se conocen adecuadamente las interrogantes. Se acepta en la actualidad la existencia de un receptor citoplásmico y/o nuclear, sin aclarar satisfactoriamente cómo las hormonas llegan hasta el núcleo. Los eventos endócrinos que se expresan rápidamente (segundos) se deben a una posible interacción con la membrana celular. El propósito de esta revisión es analizar y conciliar los datos reportados sobre el mecanismo de acción de estrogenos.