Brain mitochondrial alterations after chronic alcohol consumption.

The aim of this study was to demonstrate the existence of alterations in glutathione and cholesterol homeostasis in brain mitochondria from alcoholic rats. Glutathione concentration decreased, whereas oxidized glutathione and cholesterol contents increased in these organelles, suggesting the ethanol-induced generation of reactive oxygen species, and the impairment of mitochondrial uptake of glutathione, possibly due to the increase in cholesterol deposition. The release of apoptogenic proteins was increased after stimulating mitochondria from the brain of alcoholic rats with atractyloside. As a conclusion, chronic alcohol consumption might sensitize brain mitochondria to apoptotic stimuli, and promote the subsequent release of apoptotic proteins.

Lutein prevents the effect of high glucose levels on immune system cells in vivo and in vitro.

Diabetic patients present an increased susceptibility to frequent and protracted infections. The recognition of an impaired immune system has implications for the diagnosis, treatment and outcome of infections. Nuclear Factor kappa B (NF-kappaB) is a redox sensitive transcription factor involved in immune response, cell proliferation and apoptosis that has been associated to the development of diabetic complications. Herein we study the effects of high glucose on oxidative stress markers (malondialdeyde and glutathione contents) and NF-kappaB activity in U937 cells (a human promonocytic cell line). Furtheremore effects of lutein treatment in lymphocytes from diabetic rats was studied. The results show that high glucose induces oxidative stress in immune system cells, both in vitro and in vivo, as well as an increase in their NF-kappaB activity. It is also showed that lutein, a natural antioxidant without hypoglycemiant properties, is able to prevent all the alterations observed. Thus, this study confirms the role of oxidative stress in the immune system impairment described in diabetes, and allows the proposal of antioxidants for the clinical management of the diabetes-associated susceptibility to infections.

[Chronic ethanol feeding induces oxidative stress in the rat retina: treatment with the antioxidant ebselen]. / Estrés oxidativo en la retina de la rata inducido por la administración crónica de etanol: tratamiento con el antioxidante ebselen.

PURPOSE: To assess the involvement of biochemical and functional changes to the retina after chronic ethanol intake in adult rats, and the capacity of the antioxidant ebselen to prevent these changes. METHODS: Male Sprague-Dawley rats were used in the study. They were fed an ethanol-containing liquid diet, whereas a control group was given an ethanol-free isocaloric diet. After six weeks of experiment, the eyes were extracted and homogenized without the lens, and markers of oxidative stress were assayed, i.e., glutathione (GSH) and malondialdehyde (MDA) as an intracellular antioxidant and a lipid peroxidation product, respectively. Moreover, retinal function was assessed by electroretinogram (ERG). RESULTS: The retinal MDA concentration was significantly increased in the ethanol-fed animals compared to controls, whereas the GSH content was significantly reduced in the ethanol-fed group compared to controls. Ethanol also induced a decrease in ERG b-wave amplitude. Ebselen treatment restored the MDA and GSH concentrations and ERG b-wave amplitude to control values. CONCLUSION: These results indicate that chronic alcohol consumption alone and without the influence of nutritional factors alters the retinal redox status as well as its function (ERG). Further studies are required to better understand the protective mechanism of ebselen in this experimental model of chronic alcoholism.

Available lysine content in human milk: stability during manipulation prior to ingestion.

UNLABELLED: Available lysine content is an indicator of protein quality and nutritional value of milk. Many studies have examined the effects of extraction, treatment and storage of human milk upon its components, though no references are found regarding the possible changes in milk quality as defined by its content in essential amino acids such as lysine. The present study investigates the available lysine content in human milk and the variations in lysine resulting from milk manipulation as follows: (a) Cold storage (refrigeration at 4 degrees C for 48 hours, and frozen for 15 days at -20 degrees C); (b) Thermal treatment under conditions of low (Holder)(63 degrees C/30 minutes) and high pasteurization (75 degrees C/15 seconds). The results obtained show a decrease in milk lysine concentration after storage in both refrigerated and frozen samples. Pasteurization causes a highly significant loss of available lysine. The lysine losses were greater on applying low pasteurization versus the more gentle conditions of high pasteurization. CONCLUSIONS: While manipulation through cold storage or thermal treatment does not affect the protein content of human milk, its protein quality is modified. When human milk must be subjected to hygienization, it is preferable to apply high temperature treatment (75 degrees C, 15 seconds) than habitual pasteurization (63 degrees C, 30 minutes).

[Oxidative stress in a model of experimental diabetic retinopathy: the utility of peroxinytrite scavengers]. / Estrés oxidativo en un modelo de retinopatía diabética experimental II: utilidad de agentes secuestrantes de peroxinitritos.

PURPOSE: The retina is the neurosensorial tissue of the eye and is extremely rich in polyunsaturated lipid membranes. This feature makes it especially sensitive to oxygen and/or nitrogen activated species and lipid peroxidation. Several authors have postulated the importance of superoxide (O2-) and peroxynitrite production in the development of diabetic complications. In the present study, we have used two different antioxidants, ebselen and lutein, that present as a common feature their peroxynitrite scavenging capacity, to ameliorate the oxidative stress that exists in the retina in diabetic patients. METHODS: Hyperglycemia was accomplished by the intraperitoneal injection of Alloxan in a mouse model of diabetic retinopathy. Malondialdehyde (MDA) and glutathione (GSH) concentrations in eye homogenates (without the lens) were determined. We also recorded serial electroretinograms (ERG) and measured latency and implicit times. RESULTS: The MDA concentration increased and the GSH concentration decreased in the eyes of the diabetic animals. Treatment with ebselen and lutein restored the MDA and GSH concentrations to control values. Latency and implicit times were not affected by the diabetes. CONCLUSION: New studies are required to better understand the protective mechanism of ebselen and lutein in this model of experimental diabetic retinopathy.

[Oxidative stress in a model for experimental diabetic retinopathy: treatment with antioxidants]. / Estrés oxidativo en un modelo de retinopatía diabética experimental: tratamiento con antioxidantes.

PURPOSE: Diabetic retinopathy is the primary cause of blindness in developed countries, and though strict glycemic control is desirable to prevent complications, this is not always achievable. Thus, adjunctive therapies are needed to help in preventing or delaying the onset of diabetic complications. We have studied the biochemical and functional changes in the retina of diabetic mice, and the ability of ebselen and lutein, two antioxidants, to reverse these effects, using as a comparison the effect of insulin therapy. METHODS: Alloxan injection was used to achieve hyperglycemia. Malondialdehyde (MDA) concentration in blood and glutathione peroxidase (GPx) activity in eye homogenate were measured. Serial electroretinograms (ERG) were recorded. RESULTS: MDA concentration in the blood was high in diabetic animals. GPx activity in eye homogenate decreased in the diabetic conditions. Maximal electroretinogram amplitude decreased in diabetic animals with respect to controls. Ebselen and lutein restored MDA levels, GPx activity and ERG amplitude, and had no effect on glycemia. CONCLUSION: These results call for further studies on ebselen or lutein as adequate adjunctive therapies for diabetes.

[Chronic ethanol feeding induces oxidative stress in the optic nerve of rats]. / Estrés oxidativo en el nervio óptico de la rata inducido por la administración crónica de etanol.

PURPOSE: To assess the involvement of oxidative stress in optic nerves after chronic intake of ethanol in adult rats, when compared to animals fed with an ethanol-free isocaloric diet. METHODS: Male Sprague-Dawley rats were used throughout the study. They were fed an ethanol-containing liquid diet, whereas the pair-fed group was given an ethanol-free isocaloric diet. After six weeks of the experiment, optic nerves were extracted and markers of oxidative stress were assayed, i.e., antioxidants such as glutathione and lipid peroxidation products such as malondialdehyde (MDA). RESULTS: The GSH content in the optic nerves of ethanol-fed animals was significantly reduced, and the concentration of MDA was significantly higher in this group when compared with the pair-fed group. Time-course of body weight of animals in both groups varied identically throughout the six weeks of the experiment. CONCLUSION: The increase in lipid peroxidation products (MDA), together with the decrease in cellular antioxidants (GSH) confirm, in this experimental model, the involvement of oxidative stress in ethanol-induced toxicity of the optic nerves of rats. In view of the body weight time course, the influence of nutritional status on the parameters studied could also be discarded (Arch Soc Esp Oftalmol 2002; 77: 263-268).

Lipoic acid lessens Th1-mediated inflammation in lipopolysaccharide-induced uveitis reducing selectively Th1 lymphocytes-related cytokines release.

Inflammation results in the production of free radicals. We evaluated the anti-inflammatory and antioxidant capacity of lipoic acid in an experimental uveitis model upon a subcutaneous injection of endotoxin into Lewis rats. The role of oxidative stress in the endotoxin-induced uveitis model is well-known. Besides, the Th1 response classically performs a central part in the immunopathological process of experimental autoimmune uveitis. Exogenous sources of lipoic acid have been shown to exhibit antioxidant and anti-inflammatory properties. Our results show that lipoic acid treatment plays a preventive role in endotoxin-induced oxidative stress at 24 h post-administration and reduced Th1 lymphocytes-related cytokines by approximately 50-60%. Simultaneously, lipoic acid treatment caused a significant reduction in uveal histopathological grading and in the protein concentration in aqueous humors, but not in cellular infiltration.

Estrés oxidativo en la retina de la rata inducido por la administración crónica de etanol: tratamiento con el antioxidante ebselen / Chronic ethanol feeding induces oxidative stress in the rat retina: treatment with the antioxidant ebselen

Objetivo: Establecer la existencia de cambios bioquímicos y funcionales en la retina tras la administración crónica de etanol en ratas adultas, y estudiar la capacidad del antioxidante ebselen para corregir estos efectos. Métodos: Se utilizaron ratas macho Sprague-Dawley, que fueron alimentadas con una dieta líquida con etanol, mientras el grupo control recibió una dieta isocalórica libre de etanol. Después de seis semanas, los ojos fueron extraídos y homogenizados sin cristalino, y se determinaron parámetros relevantes en la modulación del estrés oxidativo, tales como el contenido de glutation (GSH) y de malondialdehído (MDA) como antioxidante intracelular y producto de la peroxidación de lípidos, respectivamente. Además, se comprobó la funcionalidad de la retina mediante electrorretinograma (ERG). Resultados: La concentración de MDA en la retina fue significativamente mayor en el grupo alimentado con etanol, mientras el contenido de GSH fue significativamente menor en este grupo, al compararlo con el grupo control. El etanol también indujo una disminución de la onda b del ERG. El tratamiento con ebselen fue capaz de corregir los valores de MDA, GSH y la amplitud de la onda b en el ERG hasta valores control. Conclusión: Estos resultados indican que la ingesta crónica de etanol como único factor etiológico, altera el estado redox de la retina así como su función (ERG), descartando la influencia del estado nutricional. Aun así, son necesarios nuevos estudios para confirmar el mecanismo protector del ebselen en este modelo del alcoholismo crónico

Purpose: To assess the involvement of biochemical and functional changes to the retina after chronic ethanol intake in adult rats, and the capacity of the antioxidant ebselen to prevent these changes. Methods: Male Sprague-Dawley rats were used in the study. They were fed an ethanol-containing liquid diet, whereas a control group was given an ethanol-free isocaloric diet. After six weeks of experiment, the eyes were extracted and homogenized without the lens, and markers of oxidative stress were assayed, i.e., glutathione (GSH) and malondialdehyde (MDA) as an intracellular antioxidant and a lipid peroxidation product, respectively. Moreover, retinal function was assessed by electroretinogram (ERG). Results: The retinal MDA concentration was significantly increased in the ethanol-fed animals compared to controls, whereas the GSH content was significantly reduced in the ethanol-fed group compared to controls. Ethanol also induced a decrease in ERG b-wave amplitude. Ebselen treatment restored the MDA and GSH concentrations and ERG bwave amplitude to control values. Conclusion: These results indicate that chronic alcohol consumption alone and without the influence of nutritional factors alters the retinal redox status as well as its function (ERG). Further studies are required to better understand the protective mechanism of ebselen in this experimental model of chronic alcoholism

Estrés oxidatico en un modelo de retinopatía diabética experimental II: utilidad de agentes secuestrantes de peroxinitritos / Oxidative stress in a model of experimental diabetic retinopathy: the utility of peroxinytrite scavengers

Propósito: La retina es el tejido neurosensorial del ojo y es extremadamente rica en membranas con lípidos poliinsaturados. Esta característica la hace especialmente sensible a los radicales libres derivados de oxígeno o nitrógeno y a la peroxidación lipídica. Diversos autores postulan la importancia de la producción de superóxido (O2– ) y peroxinitrito en el desarrollo de las complicaciones de la diabetes. En este trabajo hemos empleado dos antioxidantes, ebselen y luteína, que presentan la característica común de ser secuestrantes de peroxinitrito, para evitar el estrés oxidativo que la hiperglucemia induce en la retina.Métodos: La hiperglucemia se consiguió mediante la inyección de Aloxana. Se determinaron la concentración de malondialdehído (MDA) y de glutation (GSH) en homogenado de ojo. También se realizaron electrorretinogramas (ERG) de todos los animales y se midió el tiempo de latencia y de culminación.Resultados: La concentración de MDA aumentó y la de GSH disminuyó en los animales diabéticos. Los tratamientos con ebselen y luteína corrigieron las concentraciones de MDA y de GSH. El tiempo de latencia y de culminación del ERG no se ve afectado por la diabetes.Conclusión: Se requieren nuevos estudios para confirmar el mecanismo protector del ebselén y la luteína en este modelo de diabetes experimental

Purpose: The retina is the neurosensorial tissue of the eye and is extremely rich in polyunsaturated lipid membranes. This feature makes it especially sensitive to oxygen and/or nitrogen activated species and lipid peroxidation. Several authors have postulated the importance of superoxide (O2– ) and peroxynitrite production in the development of diabetic complications. In the present study, we have used two different antioxidants, ebselen and lutein, that present as a common feature their peroxynitrite scavenging capacity, to ameliorate the oxidative stress that exists in the retina in diabetic patients. Methods: Hyperglycemia was accomplished by the intraperitoneal injection of Alloxan in a mouse model of diabetic retinopathy. Malondialdehyde (MDA) and glutathione (GSH) concentrations in eye homogenates (without the lens) were determined. We also recorded serial electroretinograms (ERG) and measured latency and implicit times. Results: The MDA concentration increased and the GSH concentration decreased in the eyes of the diabetic animals. Treatment with ebselen and lutein restored the MDA and GSH concentrations to control values. Latency and implicit times were not affected by the diabetes. Conclusion: New studies are required to better understand the protective mechanism of ebselen and lutein in this model of experimental diabetic retinopathy

Estrés oxidativo en un modelo de retinopatía diabética experimental: tratamiento con antioxidantes / Oxidative Stress in a Model for Experimental Diabetic Retinopathy: Treatment with Antioxidants

Propósito: La retinopatía diabética es la primera causa de ceguera en países desarrollados, aunque lo mejor para prevenir las complicaciones es un adecuado control glucémico, este no siempre se puede conseguir. Por tanto, es necesario el uso de terapias coadyuvantes que ayuden a prevenir o retrasar la aparición de complicaciones propias de la diabetes. Se han estudiado los cambios bioquímicos y funcionales que ocurren en la retina de ratones diabéticos, y la capacidad del ebselen y la luteína, dos antioxidantes de corregir estos efectos, comparándolos con la terapia insulínica. Métodos: La hiperglucemia se consiguió mediante la inyección de Aloxana. Se determinaron la concentración sérica de Malondialdehído (MDA) y la actividad glutation peroxidasa (GPx) en homogenado de ojo. También se realizaron electroretinogramas (ERG) de todos los animales. Resultados: La concentración sérica de MDA aumentó y la actividad GPx disminuyó en los animales diabéticos. La amplitud máxima del electroretinograma disminuyó en los animales diabéticos con respecto a los controles. Los tratamientos con Ebselen y luteína corrigieron los valores de MDA, actividad GPx y amplitud en el ERG, sin tener ningún efecto sobre la glucemia. Conclusión: Estos resultados inducen nuevos estudios sobre el ebselen y la luteína como adecuadas terapias coadyuvantes en la diabetes(AU)

Purpose: Diabetic retinopathy is the primary cause of blindness in developed countries, and though strict glycemic control is desirable to prevent complications, this is not always achievable. Thus, adjunctive therapies are needed to help in preventing or delaying the onset of diabetic complications. We have studied the biochemical and functional changes in the retina of diabetic mice, and the ability of ebselen and lutein, two antioxidants, to reverse these effects, using as a comparison the effect of insulin therapy. Methods: Alloxan injection was used to achieve hyperglycemia. Malondialdehyde (MDA) concentration in blood and glutathione peroxidase (GPx) activity in eye homogenate were measured. Serial electroretinograms (ERG) were recorded. Results: MDA concentration in the blood was high in diabetic animals. GPx activity in eye homogenate decreased in the diabetic conditions. Maximal electroretinogram amplitude decreased in diabetic animals with respect to controls. Ebselen and lutein restored MDA levels, GPx activity and ERG amplitude, and had no effect on glycemia. Conclusion: These results call for further studies on ebselen or lutein as adequate adjunctive therapies for diabetes(AU)

Brain mitochondrial alterations after chronic alcohol consumption

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The aim of this study was to demonstrate the existence of alterations in glutathione and cholesterol homeostasis in brain mitochondria from alcoholic rats. Glutathione concentration decreased, whereas oxidized glutathione and cholesterol contents increased in these organelles, suggesting the ethanol-induced generation of reactive oxygen species, and the impairment of mitochondrial uptake of glutathione, possibly due to the increase in cholesterol deposition. The release of apoptogenic proteins was increased after stimulating mitochondria from the brain of alcoholic rats with atractyloside. As a conclusion, chronic alcohol consumption might sensitize brain mitochondria to apoptotic stimuli, and promote the subsequent release of apoptotic proteins (AU)

Lutein prevents the effect of high glucose levels on immune system cells in vivo and in vitro

Diabetic patients present an increased susceptibility to frequent and protractedinfections. The recognition of an impaired immune system has implications for thediagnosis, treatment and outcome of infections. Nuclear Factor kappa B (NF-êB) isa redox sensitive transcription factor involved in immune response, cell proliferationand apoptosis that has been associated to the development of diabetic complications.Herein we study the effects of high glucose on oxidative stress markers (malondialdeydeand glutathione contents) and NF-êB activity in U937 cells (a humanpromonocytic cell line). Furtheremore effects of lutein treatment in lymphocytesfrom diabetic rats was studied. The results show that high glucose induces oxidativestress in immune system cells, both in vitro and in vivo, as well as an increase in theirNF-êB activity. It is also showed that lutein, a natural antioxidant without hypoglycemiantproperties, is able to prevent all the alterations observed. Thus, this studyconfirms the role of oxidative stress in the immune system impairment described indiabetes, and allows the proposal of antioxidants for the clinical management of thediabetes-associated susceptibility to infections (AU)

No disponible

Localization of bcl-2 in the mouse brain: An anatomical study by immunohistochemistry

The presence of bcl-2 has been demonstratedin neurons of the developing adult brain ofdifferent species, including humans, the monkey,rat, rabbit and mice. Although bcl-2 expression in mouse embryo and its distribution in the central nervous system during development have been described in the cerebellar cortex and hippocampus, its distributionin the entire adult mouse brain has not yet been described. In the present work we describe bcl-2 expression in the mouse brain by immunohistochemistry and we compare it with other species showing similar patterns. We found that limbic areas have the highestbcl-2 density, suggesting a protective role ofthis protein in these regions (AU)

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Estrés oxidativo en el nervio óptico de la rata inducido por la administración crónica de etanol / Chronic ethanol feeding induces oxidative stress in the optic nerve of rats

Objetivo: Establecer la existencia de estrés oxidativo en el nervio óptico después de la administración crónica de etanol en ratas adultas, en comparación con ratas alimentadas con dieta isocalórica libre de etanol. Métodos: Se utilizaron ratas macho de la raza Sprague-Dawley, que fueron alimentadas con una dieta líquida con etanol, mientras que el grupo control recibió una dieta isocalórica libre de etanol. Después de seis semanas, se extrajeron los nervios ópticos y se determinaron parámetros relevantes en la modulación del estrés oxidativo, tales como antioxidantes -contenido de glutatión (GSH)- además de productos derivados de la peroxidación lipídica -malondialdehído (MDA). Resultados: El contenido de GSH en el nervio óptico fue significativamente menor en el grupo alimentado con etanol, mientras que la concentración de MDA fue significativamente mayor en este grupo comparado con el grupo control. Los pesos de ambos grupos oscilaron de forma idéntica durante las seis semanas de experimento. Conclusiones: El incremento de los productos de peroxidación lipídica junto con el descenso de los antioxidantes celulares, confirman en este modelo experimental la implicación del estrés oxidativo en la toxicidad del etanol en el nervio óptico de rata, y descartan la influencia del estado nutricional sobre los parámetros estudiados (AU)