Silvania Maria Mendes Vasconcelos

Oxidative stress and epilepsy: literature review.

Backgrounds. The production of free radicals has a role in the regulation of biological function, cellular damage, and the pathogenesis of central nervous system conditions. Epilepsy is a highly prevalent serious brain disorder, and oxidative stress is regarded as a possible mechanism involved in epileptogenesis. Experimental studies suggest that oxidative stress is a contributing factor to the onset and evolution of epilepsy. Objective. A review was conducted to investigate the link between oxidative stress and seizures, and oxidative stress and age as risk factors for epilepsy. The role of oxidative stress in seizure induction and propagation is also discussed. Results/Conclusions. Oxidative stress and mitochondrial dysfunction are involved in neuronal death and seizures. There is evidence that suggests that antioxidant therapy may reduce lesions induced by oxidative free radicals in some animal seizure models. Studies have demonstrated that mitochondrial dysfunction is associated with chronic oxidative stress and may have an essential role in the epileptogenesis process; however, few studies have shown an established link between oxidative stress, seizures, and age.

Behavioral alterations and pro-oxidant effect of a single ketamine administration to mice.

A growing body of evidence has pointed to the ionotropic glutamate N-methyl-d-aspartate receptor (NMDA) as an important player in the etiology of psychopathologies, including anxiety and major depression. Clinical findings suggest that ketamine may be used for the treatment of major depression. There is evidence that reactive oxygen species also play an important role in the pathogenesis of many diseases, particularly those which are neurological and psychiatric in nature. This study examined the behavioral and oxidative stress alterations after a single administration of ketamine (5, 10 and 20mg/kg i.p.) in mice. Ketamine presented a significant anxiogenic effect in the elevated plus-maze model of anxiety, also increasing locomotor activity. In the forced swimming and tail suspension tests, a significant decrease in immobility time after ketamine administration was observed. In addition to the behavioral changes induced by ketamine, this drug also increased lipid peroxidation, nitrite content and catalase activity, while decreased GSH levels in mice prefrontal cortex. In conclusion, our results confirm the antidepressant effects of ketamine, also showing a pro-oxidant effect of this drug.

Gastroprotection of (-)-α-bisabolol on acute gastric mucosal lesions in mice: the possible involved pharmacological mechanisms

(‐)‐α‐Bisabolol is an unsaturated, optically active sesquiterpene alcohol obtained by the direct distillation essential oil from plants such as Vanillosmopsis erythropappa and Matricaria chamomilla. (‐)‐α‐Bisabolol has generated considerable economic interest, since it possesses a delicate floral odor and has been shown to have anti‐septic and anti‐inflammatory activity. The aim of this work was to evaluate the gastroprotective action of (‐)‐α‐bisabolol on ethanol and indomethacin‐induced ulcer models in mice, and further investigate the pharmacological mechanisms involved in this action. The oral administration of (‐)‐α‐bisabolol 100 and 200 mg/kg was able to protect the gastric mucosa from ethanol (0.2 mL/animal p.o.) and indomethacin‐induced ulcer (20 mg/kg p.o.). Administration of l‐NAME (10 mg/kg i.p.), glibenclamide (10 mg/kg i.p.) or indomethacin (10 mg/kg p.o.) was not able to revert the gastroprotection promoted by (‐)‐α‐bisabolol 200 mg/kg on the ethanol‐induced ulcer. Dosage of gastric reduced glutathione (GSH) levels showed that ethanol and indomethacin reduced the content of non‐protein sulfhydryl (NP‐SH) groups, while (‐)‐α‐bisabolol significantly decreased the reduction of these levels on ulcer‐induced mice, but not in mice without ulcer. In conclusion, gastroprotective effect on ethanol and indomethacin‐induced ulcer promoted by (‐)‐α‐bisabolol may be associated with an increase of gastric sulfydryl groups bioavailability leading to a reduction of gastric oxidative injury induced by ethanol and indomethacin.

The contributions of antioxidant activity of lipoic acid in reducing neurogenerative progression of Parkinson's disease: a review.

ABSTRACT This work reviews the evidence of the mechanism of neuronal degeneration in Parkinsons disease (PD) and the neuroprotective effect of lipoic acid and its use in the treatment of PD. PD is characterized by slow and progressive degeneration of dopaminergic neurons of the substantia nigra pars compacta, leading to reduction of the striatal dopaminergic terminals. It is known that several factors influence neuronal damage. Among these factors, oxidative stress, immune system activity, microglial cells, and apoptotic mechanisms are of major importance. Currently, several antioxidants have been studied with the aim of reducing/slowing the progression of neurodegenerative processes. Lipoic acid is considered a universal antioxidant because it is an amphipathic substance. Lipoic acid and its reduced form, dihidrolipoic acid, act against reactive oxygen species, reducing oxidative stress. Therefore, this antioxidant has been used in the treatment of many diseases, including a new perspective for the treatment of Parkinsons disease.

Melatonin: Pharmacological Aspects and Clinical Trends

ABSTRACT Melatonin, N-acetyl-5-methoxytryptamine, the major hormone produced by the pineal gland under the influence of the dark/light cycle, has been shown to have a large number of therapeutic possibilities. It has been utilized in several countries for circadian rhythm disorders, sleep disturbances, jet lag, and sleep–wake cycle disturbances in blind people, and shift workers. In our mechanism of act, the Gi protein-coupled metabotropic melatonin receptors MT1 and MT2 are the primary mediators of the physiological actions of melatonin. This hormone plays an important role in the regulation of physiological and neuroendocrine functions, such as synchronization of seasonal reproductive rhythms and entrainment of circadian cycles. In addition to its chronobiological role, several pharmacological effects of melatonin have been reported in mammals including sedative, antioxidant, anxiolytic, antidepressant, anticonvulsant, and analgesic activities. There is some evidence from clinical trials that melatonin can be helpful in that event. Current trends of pharmacological functions of melatonin pointed out its use in the treatment of neurodegenerative and neoplastic diseases. These effects and uses of melatonin are mentioned but further confirmatory studies are needed in most of them.

CSC, an adenosine A2A receptor antagonist and MAO B inhibitor, reverses behavior, monoamine neurotransmission, and amino acid alterations in the 6-OHDA-lesioned rats

The present work showed the effects of 8-(-3-chlorostyryl)-caffeine (CSC), an A(2A) receptors antagonist and MAO B inhibitor, on behavior and biochemical alterations in 6-OHDA-lesioned rats. Male Wistar rats (280 g) were injected with CSC (1 and 5 mg/kg, i.p.) alone or combined with l-DOPA (50 mg/kg+benserazide 12.5 mg/kg), starting 6 days after the striatal 6-OHDA lesions, and once daily for the next 7 days. Fourteen days after the 6-OHDA lesion (and 24 h after CSC or vehicle), the number of net body rotations/h (after the apomorphine challenge) was recorded and, at the next day, animals were sacrificed. The ipsilateral striatum was used for HPLC measurements of monoamines and amino acids or for determination of nitrite contents and lipid peroxidation. Results showed that the increase in body rotation, induced by the 6-OHDA lesion, after the apomorphine challenge, was significantly and dose-dependently reversed by CSC. Furthermore, the decreased striatal levels of DA and metabolites, in the 6-OHDA-lesioned rats, were reversed after CSC treatment, and these effects were potentiated after the combination with l-DOPA. Similar results were observed with NE, 5-HT and 5-HIAA. While glutamate and GABA were increased in the 6-OHDA-lesioned group, CSC alone or mainly combined with l-DOPA reversed these alterations. In addition, the CSC treatment of 6-OHDA-lesioned rats reversed the increased nitrite formation and lipid peroxidation induced by 6-OHDA. In conclusion, CSC by means of its dual action as A(2A) antagonist and MAO-B inhibitor reversed behavior and biochemical alterations, observed in the 6-OHDA-lesioned rats, pointing out to its potential benefit for the treatment of PD.

Differential Effects of Cocaine-Induced Seizures and Lethality on M1-Like Muscarinic and Dopaminergic D1- and D2-Like Binding Receptors in Mice Brain

SummaryThis work was designed to study the changes produced by cocaine-induced seizures and lethality on dopaminergic D1- and D2-like receptors, muscarinic M1-like binding sites, as well as acetylcholinesterase activity in mice prefrontal cortex (PFC) and striatum (ST). Binding assays were performed in brain homogenates from the PFC and ST and ligands used were [3H]-N-methylscopolamine, [3H]-NMS (in the presence of carbachol), [3H]-SCH 23390 and [3H]-spiroperidol (in presence of mianserin), for muscarinic (M1-like), D1- and D2-like receptors, respectively. Brain acetylcholinesterase (AChE) activity was also determined in these brain areas. Cocaine-induced SE decreased [3H]-SCH 23390 binding in both ST and PFC areas. A decrease in [3H]-NMS binding and an increase in [3H]-spiroperidol binding in PFC was also observed. Cocaine-induced lethality increased [3H]-spiroperidol binding in both areas and decreased [3H]-NMS binding only in PFC, while no difference was seen in [3H]-SCH 23390 binding. Neither SE, nor lethality altered [3H]-NMS binding in ST. AChE activity increased after SE in ST while after death the increase occurred in both PFC and ST. In conclusion, cocaine-induced SE and lethality produces differential changes in brain cholinergic and dopaminergic receptors, depending on the brain area studied suggesting an extensive and complex involvement of these with cocaine toxicity in central nervous system.

Care of nursing team to children with peripheral venous puncture: descriptive study

Objetivo Objetivou-se identificar os cuidados da equipe de enfermagem a crianca ante a puncao venosa periferica e descrever os sentimentos da crianca puncionada pelo profissional de enfermagem. Metodo Pesquisa exploratoria-descritiva, realizada com 59 criancas, por meio de um formulario, entre outubro/2010 a janeiro/2011 em um hospital pediatrico de Fortaleza-CE, Brasil. Resultados O medo e a dor foram os sentimentos mais relatados pelas criancas ao serem puncionadas (69,4%) pelos profissionais de enfermagem. Conclusao Concluiu-se que o medo ainda e um sentimento muito evidente entre a clientela infantil, demonstrando assim a necessidade de maior atencao ao preparo da crianca para a puncao venosa periferica. Portanto, aponta-se a relevância de maiores discussoes, capacitacao e sensibilizacao da equipe de enfermagem que atua em pediatria acerca dos cuidados a crianca sob puncao venosa periferica. Descritores : Servicos de Saude da Crianca, Cuidados de Enfermagem, Puncoes, Enfermagem. Recebido: 12/08/2011 Aprovado: 13/03/2012

Antimanic activity of minocycline in a GBR12909-induced model of mania in mice: Possible role of antioxidant and neurotrophic mechanisms

BACKGROUND Mania/hypomania is the cardinal feature of bipolar disorder. Recently, single administration of the dopamine transporter (DAT) inhibitor, GBR12909, was related to mania-like alterations. In the present study we aimed at testing behavioral and brain oxidant/neurotrophic alterations induced by the repeated administration of GBR12909 and its prevention/reversal by the mood stabilizing drugs, lithium (Li) and valproate (VAL) as well as by the neuroprotective drug, minocycline (Mino). METHODS Adult Swiss mice were submitted to 14 days protocols namely prevention and reversal. In the reversal protocol mice were given GBR12909 or saline and between days 8 and 14 received Li, VAL, Mino (25 or 50mg/kg) or saline. In the prevention treatment, mice were pretreated with Li, VAL, Mino or saline prior to GBR12909. RESULTS GBR12909 repeated administration induced hyperlocomotion and increased risk taking behavior that were prevented and reversed by the mood stabilizers and both doses of Mino. Li, VAL or Mino were more effective in the reversal of striatal GSH alterations induced by GBR12909. Regarding lipid peroxidation Mino was more effective in the prevention and reversal of lipid peroxidation in the hippocampus whereas Li and VAL prevented this alteration in the striatum and PFC. Li, VAL and Mino25 reversed the decrease in BDNF levels induced by GBR12909. CONCLUSION GBR12909 repeated administration resembles manic phenotype. Similarly to classical mood-stabilizing agents, Mino prevented and reversed GBR12909 manic-like behavior in mice. Thus, our data provide preclinical support to the design of trials investigating Minos possible antimanic effects.