RESUMO
The Wistar Audiogenic Rat (WAR) strain is a genetic model of epilepsy, specifically brainstem-dependent tonic-clonic seizures, triggered by acute auditory stimulation. Chronic audiogenic seizures (audiogenic kindling) mimic temporal lobe epilepsy, with significant participation of the hippocampus, amygdala, and cortex. The objective of the present study was to characterize the mitochondrial energy metabolism in hippocampus and cortex of WAR and verify its relationship with seizure severity. Hippocampus of WAR naïve (no seizures) presented higher oxygen consumption in respiratory states related to the maximum capacities of phosphorylation and electron transfer system, elevated mitochondrial density, lower GSH/GSSG and catalase activity, and higher protein carbonyl and lactate contents, compared with their Wistar counterparts. Audiogenic kindling had no adding functional effect in WAR, but in Wistar, it induced the same alterations observed in the audiogenic strain. In the cortex, WAR naïve presented elevated mitochondrial density, lower GSH/GSSG and catalase activity, and higher protein carbonyl levels. Chronic acoustic stimulation in Wistar induced the same alterations in cortex and hippocampus. Mainly in the hippocampus, WAR naïve presented elevated mRNA expression of glucose, lactate and excitatory amino acids transporters, several glycolytic enzymes, lactate dehydrogenase, and Na+/K+ ATPase in neurons and in astrocytes. In vivo treatment with mitochondrial uncoupler 2,4-dinitrophenol (DNP) or N-acetylcysteine (NAC) in WAR had no effect on mitochondrial metabolism, but lowered oxidative stress. Unlike DNP, NAC downregulated all enzyme genes involved in glucose and lactate uptake, and metabolism in neurons and astrocytes. Additionally, it was able to reduce brainstem seizure severity in WAR. In conclusion, in WAR naïve animals, both cerebral cortex and hippocampus display elevated mitochondrial density and/or activity associated with oxidative damage, glucose and lactate metabolism pathways upregulation, and increased Na+/K+ ATPase mRNA expression. Only in vivo treatment with NAC was able to reduce seizure severity of kindled WARs, possibly via down regulation of glucose/lactate metabolism. Taken together, our results are a clear contribution to the field of mitochondrial metabolism associated to epileptic seizures.
RESUMO
Oxidative stress can be regarded as an imbalance between the amount of reactive oxygen species (ROS) and the ability of a biological system to eliminate the toxic species and repair the resulting damages. Since the germinating seeds and the resulted seedlings are rich in enzymes, whereas the treatment with chemicals affects much the seed germination, producing also ROS, we evaluate here the influence of 2,4-dinitrophenol (DNP) and potassium iodate (KIO3) on wheat germination (Triticum aestivum L.) and seedlings growth. Germination rate, the masses and heights of the 7 day old seedlings, as well as the activity of some enzymes involved in the oxidative stress such as peroxidase, catalase and superoxide dismutase were measured seven days after the chemical treatment. The treatment of the wheat seeds with 10-5 - 10-3 M solutions of DNP resulted in a relative concentration-dependent inhibition of the germination, with a concomitant stimulation of the weight and height of viable seedlings. The Gasparom variety treated with 10-5 M KIO3 showed a slight increase in the germination rate in comparison with the control batch. The two tested substances determined a significantly modified response of the oxidative stress enzymes, especially in the seeds treated with 10-4 and 10-3 M solutions.
RESUMO
BACKGROUND: Type 2 diabetes (T2D) and heart failure (HF) are associated with high levels of skeletal muscle (SkM) oxidative stress (OS). Health benefits attributed to flavonoids have been ascribed to antioxidation. However, for flavonoids with similar antioxidant potential, end-biological effects vary widely suggesting other mechanistic venues for reducing OS. Decreases in OS may follow the modulation of key regulatory pathways including antioxidant levels (e.g. glutathione) and enzymes such as mitochondrial superoxide dismutase (SOD2) and catalase. METHODS: We examined OS-related alterations in SkM in T2D/HF patients (as compared vs. healthy controls) and evaluated the effects of three-month treatment with (-)-epicatechin (Epi) rich cocoa (ERC). To evidence Epi as the mediator of the improved OS profile we examined the effects of pure Epi (vs. water) on SkM OS regulatory systems in a mouse model of insulin resistance and contrasted results vs. normal mice. RESULTS: There were severe alterations in OS regulatory systems in T2D/HF SkM as compared with healthy controls. Treatment with ERC induced recovery in glutathione levels and decreases in the nitrotyrosilation and carbonylation of proteins. With treatment, key transcriptional factors translocate into the nucleus leading to increases in SOD2 and catalase protein expression and activity levels. In insulin resistant mice, there were alterations in muscle OS and pure Epi replicated the beneficial effects of ERC found in humans. CONCLUSIONS: Major perturbations in SkM OS can be reversed with ERC in T2D/HF patients. Epi likely mediates such effects and may provide an effective means to treat conditions associated with tissue OS.
Assuntos
Cacau , Catequina/administração & dosagem , Diabetes Mellitus Tipo 2/metabolismo , Insuficiência Cardíaca/metabolismo , Músculo Esquelético/metabolismo , Estresse Oxidativo/fisiologia , Idoso , Animais , Bebidas , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Músculo Esquelético/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Projetos PilotoRESUMO
El presente artículo busca adelantar un análisis libre de la evolución del desarrollo del Sistema General de Seguridad Social en Salud, desde su implementación mediante la promulgación de la Ley 100 de 1993 y las posteriores normas que la han complementado.En su primera parte realiza un breve recorrido por el sistema, tomando como puntos de referencia los principios fundamentales establecidos para el mismo, tanto en la constitución nacional, como dentro de la misma Ley 100, para luego continuar con una visión crítica de la misma, buscando determinar las principales fallas y puntos álgidos por donde la corrupción la ha flagelado, al igual que ubicando los actores que se han beneficiado, lo mismo que los grandes perdedores tanto en el desarrollo del sistema como en sus resultados.Una vez concluido el proceso de crítica y análisis, el artículo deja en claro una posición respecto al Sistema General de Seguridad Social, en cuanto a las lógicas estructurales que lo fundamentan y adicionando un juicio digno de un mas amplio debate, sobre el papel adelantado por los profesionales de la salud, tanto en la ejecución del mismo, como en su participación como agentes activos generadores de cambio.
This article wants to make a free analysis about thedevelopment of the General Social Security Systemfrom the moment it was implemented by virtue ofLaw 30, 1993 and further complementaryregulations. First of all, it briefly analysis the system,taking as a reference the established principles, theNational Constitution, and the Law 100; then, itcontinues with a critical view of it in order to determinethe main failures and decisive points wherecorruption has severely criticized it; it has alsolocated some actors who have taken advantage of it,and some others who have been losers both in thedevelopment of the system and in its results. Oncethe process of criticism and analysis has beenconcluded, this article presents a clear position aboutthe General Social Security Health System, regardingstructural logic it is based on, and it also adds ajudgment worthy of a broader discussion on therole of the health professionals, both in their performanceand as active actors to generate a change.