RESUMEN
Male rats of 80-90â¯g that were fed 42â¯days with a commercial rodent diet of 2780â¯kcal/100â¯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.
Asunto(s)
Encéfalo/metabolismo , Cobre/metabolismo , Hierro/metabolismo , Metales/metabolismo , Animales , Glutatión/metabolismo , Peroxidación de Lípido , Estrés Oxidativo , RatasRESUMEN
Male rats of 80-90â¯g were overloaded with either Fe(II) or Cu(II) for 42â¯days by high concentrations of FeCl2 or CuSO4 in the drinking water. The animals were fed with a commercial rodent diet of 2780â¯kcal/100â¯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.
Asunto(s)
Cobre/metabolismo , Homeostasis , Sobrecarga de Hierro/metabolismo , Hierro/metabolismo , Hígado/metabolismo , Animales , Enfermedad Crónica , Humanos , Hígado/patología , Masculino , Oxidación-Reducción , Ratas , Ratas Sprague-DawleyRESUMEN
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.
Asunto(s)
Síndrome Hemolítico-Urémico/etiología , Estrés Oxidativo , Toxina Shiga II/metabolismo , Acetilcisteína/farmacología , Animales , Cisteína/análogos & derivados , Cisteína/farmacología , Modelos Animales de Enfermedad , Glutatión/metabolismo , Peroxidación de Lípido , Masculino , Malondialdehído/metabolismo , Ratones , Oxidación-Reducción/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Escherichia coli Shiga-Toxigénica/metabolismoRESUMEN
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.
Asunto(s)
Mucosa Gástrica/efectos de los fármacos , Estrés Oxidativo , Sesquiterpenos/química , Etanol/toxicidad , Humanos , Mediadores de Inflamación/metabolismo , Plantas Medicinales/química , Sesquiterpenos/uso terapéutico , Gastropatías/inducido químicamente , Gastropatías/tratamiento farmacológicoRESUMEN
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.
Asunto(s)
Enfermedad de Alzheimer/sangre , Glucemia/análisis , Demencia Vascular/sangre , Diabetes Mellitus Tipo 2/sangre , Hemoglobina Glucada/análisis , Insulina/sangre , Anciano , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/patología , Encéfalo/patología , Demencia Vascular/complicaciones , Demencia Vascular/patología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/patología , Femenino , Humanos , Imagen por Resonancia Magnética , MasculinoRESUMEN
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.
Asunto(s)
Antiulcerosos/farmacología , Antioxidantes/farmacología , Artemisia , Lactonas/farmacología , Plantas Medicinales , Sesquiterpenos/farmacología , Úlcera Gástrica/tratamiento farmacológico , Antiulcerosos/uso terapéutico , Antioxidantes/uso terapéutico , Argentina , Etanol/efectos adversos , Mucosa Gástrica/metabolismo , Humanos , Lactonas/uso terapéutico , Medicina Tradicional , Estrés Oxidativo/efectos de los fármacos , Sesquiterpenos/uso terapéutico , Solventes/efectos adversos , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/metabolismoRESUMEN
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
Asunto(s)
Humanos , Antiulcerosos , Antioxidantes , Artemisia , Lactonas , Plantas Medicinales , Sesquiterpenos , Úlcera Gástrica , Antiulcerosos , Antioxidantes , Argentina , Lactonas , Medicina Tradicional , Estrés Oxidativo , SesquiterpenosRESUMEN
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.