Graziela de Oliveira Schmitt

Induction of lipid peroxidation and decrease of antioxidant defenses in symptomatic and asymptomatic patients with X-linked adrenoleukodystrophy.

Patients affected by X‐linked adrenoleukodystrophy (X‐ALD) present a progressive brain and peripheral demyelination and adrenal cortex insufficiency, associated with accumulation of the very long chain fatty acids (VLCFA) hexacosanoic acid (C26:0) and tetracosanoic acid (C24:0) in different tissues and biological fluids. X‐ALD is characterized by heterogeneous clinical phenotypes. Seven clinical variants have been described for this genetic disorder, being the childhood cerebral form (CCER), adrenomyeloneuropathy (AMN) and asymptomatic the most common clinical forms. In a previous work, we showed evidence that oxidative stress is involved in the pathophysiology of X‐ALD symptomatic patients. In the present study, we compared oxidative stress parameters, namely thiobarbituric acid reactive substances (TBA‐RS) and total antioxidant status (TAS), in plasma from patients with CCER, AMN and in asymptomatic X‐ALD patients. It was observed that symptomatic and asymptomatic X‐ALD patients presented a significant increase of plasma TBA‐RS measurement, indicating a stimulation of lipid peroxidation. Furthermore, lipid peroxidation was higher in AMN, as compared to CCER and asymptomatic patients. We also observed that the total antioxidant defenses (TAS) were decreased in symptomatic but not in asymptomatic X‐ALD patients. Therefore, it may be presumed that asymptomatic patients seem to be protected against oxidative stress because of their normal antioxidant defenses and that other factors besides oxidative damage may be responsible for the severity of the symptoms in X‐ALD and need to be investigated.

Oxidative stress parameters in diabetic rats submitted to forced swimming test: the clonazepam effect

Diabetes-associated depression may occur due to changes in the quality of life imposed by treatment, or may be a consequence of the biochemical changes accompanying the disease. We evaluated the oxidative stress from diabetic animals submitted to an experimental model of depression and the effects of clonazepam. Male Wistar rats were induced to diabetes with streptozotocin and submitted to forced swimming test. Clonazepam was administered 24, 5 and 1 h before test. The animals were sacrificed by decapitation, and plasma and erythrocytes were separated, as well as hippocampus, cortex and striatum. Reactive species of thiobarbituric acid (TBARS) and total antioxidant reactivity (TAR) as well as antioxidant enzyme activities catalase (CAT) and superoxide dismutase (SOD) were evaluated. Results showed a significant increase of TBARS and a significant decrease of TAR in plasma from diabetic animals, which was altered by clonazepam. There were no effects of CAT and SOD activities in erythrocytes from tested animals. The results observed in hippocampus showed a significant increase of TBARS from diabetic rats, altered by clonazepam, and no one alteration was verified in TAR. The significant increase of TBARS and the significant decrease of TAR in cortex from diabetic rats were not altered by clonazepam administration. There were no alterations of TBARS and TAR in striatum from tested animals. Besides, clonazepam reverses the immobility in diabetic rats. Considering the action of clonazepam, it is suggested that it could be an alternative therapeutic for depression to diabetic patients, once it could give a protection against free radicals.

Oxidative stress is induced in female carriers of X-linked adrenoleukodystrophy

X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disease biochemically characterized by the accumulation of very long chain fatty acids (VLCFA), particularly hexacosanoic (C26:0) and tetracosanoic acids (C24:0) in different tissues and in biological fluids and clinically characterized by central and peripheral demyelination and adrenal insufficiency. A considerable number of heterozygotes (HTZ) for X-ALD develop neurological symptoms like spinal cord involvement resembling milder forms of adrenomyeloneuropathy. However, the mechanisms of brain damage in hemizygotes and heterozygotes X-ALD individuals are poorly understood. Considering that oxidative stress was involved in various neurodegenerative disorders and that in a previous study we showed evidence that oxidative stress is probably involved in the pathophysiology of X-ALD symptomatic patients, in the present study we evaluated various oxidative stress parameters, namely thiobarbituric acid-reactive substances (TBA-RS), total antioxidant status (TAS) and total antioxidant reactivity (TAR) in plasma of HTZ individuals for X-ALD. It was observed that female carriers present a significant increase of TBA-RS measurement, indicating a stimulation of lipid peroxidation, as well as a decrease of TAR, reflecting a deficient capacity to rapidly handle an increase of reactive species. These results indicate that oxidative stress is involved in the pathophysiology of heterozygotes for X-ALD.

Erythrocyte glutathione peroxidase activity and plasma selenium concentration are reduced in maple syrup urine disease patients during treatment

Maple syrup urine disease (MSUD) is an inherited disorder caused by a deficiency of the branched‐chain α‐keto acid dehydrogenase complex activity. In the present study we evaluated selenium levels in plasma from MSUD patients at diagnosis and under treatment and the activities of glutathione peroxidase, catalase and superoxide dismutase in erythrocytes from treated patients. We verified that MSUD patients present a significant selenium deficiency at diagnosis, which becomes more pronounced during treatment, as well as a decrease of erythrocyte glutathione peroxidase activity during treatment. In contrast, erythrocyte catalase and superoxide dismutase activities were not altered in these patients. Our present results suggest that the reduction of an important antioxidant enzyme activity may be partially involved in the pathomechanisms of this disorder and that plasma selenium levels must be corrected through dietary supplementation in MSUD patients.