Brain oxidative stress in rat with chronic iron or copper overload.

Male rats of 80-90 g that were fed 42 days with a commercial rodent diet of 2780 kcal/100 g and received chronic overloads of either Fe(II) or Cu(II) in the drinking water. The two metals produced brain oxidative stress and damage with marked increases in the indicators of oxidative processes: in vivo brain surface chemiluminescence (the sensitive organ non-invasive assay for oxidative free radical reactions), and the ex vivo processes of phospholipid peroxidation and protein oxidation. Brain redox imbalance was also indicated by marked decreases in the cellular indicators of oxidative metabolic stress: reduced glutathione (GSH) content and reduced/oxidized glutathione ratio (GSH/GSSG). Brain decreased GSH content has a central role in the biochemical oxidative processes associated with Fe and Cu chronic damage. The understanding of biochemical oxidative imbalances in the rat brain with chronic Fe(II) or Cu(II) overloads may be useful for the establishment of pharmacological therapies for human pathologies associated to Fe and Cu cellular imbalances.

Redox dyshomeostasis in the experimental chronic hepatic overloads with iron or copper.

Male rats of 80-90 g were overloaded with either Fe(II) or Cu(II) for 42 days by high concentrations of FeCl2 or CuSO4 in the drinking water. The animals were fed with a commercial rodent diet of 2780 kcal/100 g. Both metal treatments led to a liver redox imbalance and dyshomeostasis with oxidative stress and damage and the concomitant enhancement of oxidative processes as indicated by in vivo surface liver chemiluminescence, the sensitive and organ non-invasive assay for oxidative free radical reactions, and by ex vivo determined processes of phospholipid peroxidation and protein oxidation. In parallel, marked decreases in the antioxidant defense were observed. Liver reduced glutathione (GSH) content and the reduced/oxidized glutathione ratio (GSH/GSSG) were early indicators of oxidative metabolic disturbance upon the metal overloads. Thus, GSH plays a central role in the defense reactions involved in the chronic toxicity of Fe and Cu. Chronic overloads of Fe or Cu in rats afford an experimental animal model of hemochromatosis and of Wilson's disease, respectively. These two animal models could be useful in the study and development of the beneficial effects of pharmacological interventions in the two human diseases.

Enfermedad de Alzheimer y deterioro cognitivo asociado a la diabetes mellitus de tipo 2: relaciones e hipótesis / Alzheimer disease and cognitive impairment associated with diabetes mellitus type 2: Associations and a hypothesis

Introducción: Varios estudios epidemiológicos han demostrado que los pacientes de diabetes mellitus de tipo 2 presentan un aumento de riesgo para adquirir enfermedad de Alzheimer, pero las relaciones entre ellas no están aclaradas. Desarrollo: Ambas enfermedades presentan similares anormalidades metabólicas: Alteraciones en el metabolismo de la glucosa, irregularidades en los receptores para la señalización de la insulina, estrés oxidativo, anomalías en la conformación de proteínas y depósitos de β-amiloide. A través del desarrollo de investigaciones experimentales en las últimas 2 décadas, han sido postuladas diversas hipótesis. Una de las más llamativas relaciona los daños microvasculares de la polineuritis diabética con los cambios que se producen en el sistema nervioso central en la enfermedad de Alzheimer. Otra hipótesis considera que en ambas enfermedades la evolución del deterioro cognitivo está vinculada con el estado de estrés oxidativo sistémico. Más recientemente, en pacientes con enfermedad de Alzheimer con diabetes mellitus de tipo 2 concomitante, se ha comprobado la existencia de atenuación en el deterioro cognitivo y la normalización en los valores de variables bioquímicas marcadoras del estrés oxidativo. Los fármacos antidiabéticos podrían ejercer un efecto favorable sobre la glucólisis, sus productos finales y otras alteraciones metabólicas. Conclusiones:Los pacientes diabéticos presentan mayor riesgo para desarrollar Alzheimer, pero, paradójicamente, las alteraciones bioquímicas y el deterioro cognitivo resultan menores que en los grupos de pacientes dementes sin diabetes mellitus. La mejor comprensión de las patogenias que interactúan en estas enfermedades quizás sustente nuevas estrategias terapéuticas conducentes a disminuir o detener la progresión de los deterioros

Introduction: Epidemiological studies have demonstrated that patients with diabetes mellitus have an increased risk of developing Alzheimer disease, but the relationship between the 2 entities is not clear. Development: Both diseases exhibit similar metabolic abnormalities: disordered glucose metabolism, abnormal insulin receptor signalling and insulin resistance, oxidative stress, and structural abnormalities in proteins and β-amyloid deposits. Different hypotheses have emerged from experimental work in the last two decades. One of the most comprehensive relates the microvascular damage in diabetic polyneuritis with the central nervous system changes occurring in Alzheimer disease. Another hypothesis considers that cognitive impairment in both diabetes and Alzheimer disease is linked to a state of systemic oxidative stress. Recently, attenuation of cognitive impairment and normalisation of values in biochemical markers for oxidative stress were found in patients with Alzheimer disease and concomitant diabetes. Antidiabetic drugs may have a beneficial effect on glycolysis and its end products, and on other metabolic alterations. Conclusions: Diabetic patients are at increased risk for developing Alzheimer disease, but paradoxically, their biochemical alterations and cognitive impairment are less pronounced than in groups of dementia patients without diabetes. A deeper understanding of interactions between the pathogenic processes of both entities may lead to new therapeutic strategies that would slow or halt the progression of impairment

Alzheimer disease and cognitive impairment associated with diabetes mellitus type 2: associations and a hypothesis.

INTRODUCTION: Epidemiological studies have demonstrated that patients with diabetes mellitus have an increased risk of developing Alzheimer disease, but the relationship between the 2 entities is not clear. DEVELOPMENT: Both diseases exhibit similar metabolic abnormalities: disordered glucose metabolism, abnormal insulin receptor signalling and insulin resistance, oxidative stress, and structural abnormalities in proteins and ß-amyloid deposits. Different hypotheses have emerged from experimental work in the last two decades. One of the most comprehensive relates the microvascular damage in diabetic polyneuritis with the central nervous system changes occurring in Alzheimer disease. Another hypothesis considers that cognitive impairment in both diabetes and Alzheimer disease is linked to a state of systemic oxidative stress. Recently, attenuation of cognitive impairment and normalisation of values in biochemical markers for oxidative stress were found in patients with Alzheimer disease and concomitant diabetes. Antidiabetic drugs may have a beneficial effect on glycolysis and its end products, and on other metabolic alterations. CONCLUSIONS: Diabetic patients are at increased risk for developing Alzheimer disease, but paradoxically, their biochemical alterations and cognitive impairment are less pronounced than in groups of dementia patients without diabetes. A deeper understanding of interactions between the pathogenic processes of both entities may lead to new therapeutic strategies that would slow or halt the progression of impairment.

The oxidative stress induced in vivo by Shiga toxin-2 contributes to the pathogenicity of haemolytic uraemic syndrome.

Typical haemolytic uraemic syndrome (HUS) is caused by Shiga toxin (Stx)-producing Escherichia coli infections and is characterized by thrombotic microangiopathy that leads to haemolytic anaemia, thrombocytopenia and acute renal failure. Renal or neurological sequelae are consequences of irreversible tissue damage during the acute phase. Stx toxicity and the acute inflammatory response raised by the host determine the development of HUS. At present there is no specific therapy to control Stx damage. The pathogenic role of reactive oxygen species (ROS) on endothelial injury has been largely documented. In this study, we investigated the in-vivo effects of Stx on the oxidative balance and its contribution to the development of HUS in mice. In addition, we analysed the effect of anti-oxidant agents as therapeutic tools to counteract Stx toxicity. We demonstrated that Stx induced an oxidative imbalance, evidenced by renal glutathione depletion and increased lipid membrane peroxidation. The increased ROS production by neutrophils may be one of the major sources of oxidative stress during Stx intoxication. All these parameters were ameliorated by anti-oxidants reducing platelet activation, renal damage and increasing survival. To conclude, Stx generates a pro-oxidative state that contributes to kidney failure, and exogenous anti-oxidants could be beneficial to counteract this pathogenic pathway.

Bioactivity of sesquiterpenes: compounds that protect from alcohol-induced gastric mucosal lesions and oxidative damage.

Sesquiterpene lactones of the guaianolide and eudermanolide types are considered of interest because they have an effect in the regulation and prevention of oxidative damage and inflammation-mediated biological damage. Dehydroleucodine, a natural sesquiterpene isolated from Artemisia douglasiana Besser, and ilicic aldehyde, a semi-synthetic sesquiterpene lactones, showed in vivo protection in ethanol-induced gastric mucosa damage. This action was determined by in situ gastric mucosa chemiluminescence and by tissue antioxidant content.

Insulin, glucose and glycated hemoglobin in Alzheimer's and vascular dementia with and without superimposed Type II diabetes mellitus condition.

Increased concentrations of insulin, glucose and glycohemoglobin are associated with Type II diabetes mellitus (DM) and recognized as characteristic markers of the disease; in Alzheimer's (AD), Vascular dementia (VaD), and both dementia's with superimposed diabetes (AD + DM, VaD + DM) the knowledge is scarce. The sample (n = 122; males = 60; mean age = 73 +/- 7) comprised DM, AD, VaD, AD + DM, and VaD + DM patients, and healthy controls (C). The ANOVA's yielded significant differences between groups: Insulin p = 3.7 x 10(-3); Glucose p < 10(-12); Glycohemoglobin p = 9.2x10(-4). Comparisons between groups (DM vs. C, AD + DM vs. AD, VaD + DM vs. VaD, and demented DM vs. non-demented DM) resulted significant for all variables (Bonferroni's statistic, alpha = 0.05). Diabetic and diabetic demented patients presented significant increases largely different from controls (0.01 < p < 0.001), unlike the non-significant changes in their non-diabetic counterparts; linear relationships were found across all groups. The correlation's insulin/glucose and insulin/glycohemoglobin change to positive within demented groups, indicating a different performance of insulin in demented and non-demented subjects.

Antioxidant properties of natural compounds used in popular medicine for gastric ulcers.

There is evidence concerning the participation of reactive oxygen species in the etiology and physiopathology of human diseases, such as neurodegenerative disorders, inflammation, viral infections, autoimmune pathologies, and digestive system disorders such as gastrointestinal inflammation and gastric ulcer. The role of these reactive oxygen species in several diseases and the potential antioxidant protective effect of natural compounds on affected tissues are topics of high current interest. To consider a natural compound or a drug as an antioxidant substance it is necessary to investigate its antioxidant properties in vitro and then to evaluate its antioxidant functions in biological systems. In this review article, we shall consider the role of natural antioxidants derived from popular plants to reduce or prevent the oxidative stress in gastric ulcer induced by ethanol.

Antioxidant properties of natural compounds used in popular medicine for gastric ulcers

There is evidence concerning the participation of reactive oxygen species in the etiology and physiopathology of human diseases, such as neurodegenerative disorders, inflammation, viral infections, autoimmune pathologies, and digestive system disorders such as gastrointestinal inflammation and gastric ulcer. The role of these reactive oxygen species in several diseases and the potential antioxidant protective effect of natural compounds on affected tissues are topics of high current interest. To consider a natural compound or a drug as an antioxidant substance it is necessary to investigate its antioxidant properties in vitro and then to evaluate its antioxidant functions in biological systems. In this review article, we shall consider the role of natural antioxidants derived from popular plants to reduce or prevent the oxidative stress in gastric ulcer induced by ethanol

Peripheral markers of oxidative stress in probable Alzheimer patients.

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.