Oxidative stress, a state of imbalance in the production of reactive oxygen species and nitrogen, is induced by a wide variety of factors. This biochemical state is associated with systemic diseases, and diseases affecting the central nervous system. Epilepsy is a chronic neurological disorder with refractoriness to drug therapy at about 30%. Currently, experimental evidence supports the involvement of oxidative stress in seizures, in the process of their generation, and in the mechanisms associated with refractoriness to drug therapy. Hence, the aim of this review is to present information in order to facilitate the handling of this evidence and determine the therapeutic impact of the biochemical status for this pathology.
The aim was to evaluate the effect of toluene and nutritional status on levels of serotonin (5-HT), 5-hydroxytryptophan (5-HTP), Na+/K+-ATPase, total ATPase and lipid peroxidation (TBARS) in rat brain. Study was conducted with malnourished (MN), well-nourished (WN) and normal Wistar rats. Three groups were formed for each nutritional status: control group I received 0.9% NaCl; toluene (1 g/kg) was administered to group II, and 1.5 g/kg to group III. Levels of 5-HT decreased (P< 0.05) in WN toluene groups, and 5-HTP decreased (P < 0.05) in the WN 1 g toluene and MN 1.5 g toluene groups. TBARS decreased (P < 0.05) in WN toluene groups. A trend to increase in Na+/K+-ATPase was found in WN and MN toluene groups, while total ATPase increased (P < 0.05) in the WN 1.5 g toluene group. The results suggest that high concentrations of toluene in single doses induce significant changes in the serotonergic system and alter membrane fluidity more perceptibly in the brain of adult animals with regular diet than in malnourished animals.
A number of experimental and clinical reports suggest the involvement of oxidative stress in pathophysiology of epilepsy. Topiramate, a new antiepileptic drug, induces antioxidant effect in epileptic animals. However, to date, no further studies appear to be carried out in order to demonstrate the ability of topiramate to act as antioxidant. Therefore, the objective of this work was to evaluate the in vitro superoxide (O₂(·-)), hydroxyl radical (OH·), hypochlorous acid (HOCl), hydrogen peroxide (H₂O₂), singlet oxygen ((1)O₂) and peroxynitrite (ONOO(-)) scavenging capacity of topiramate in comparison with reference compounds. In addition, we investigated the possible antitumour activity of this compound in some cancer cell lines. Topiramate displays a scavenging capacity compared to the reference compound, with the exception of ONOO(-), although it was less efficient than nordihydroguaiaretic acid, dimethylthiourea, ascorbic acid, sodium pyruvate and glutathione for O₂(·-), OH·, HOCl, H₂O₂ and (1)O₂(P < 0.0001), respectively, and not induced significant growth inhibition in cancer cell lines. The direct antioxidant properties of topiramate could explain the neuroprotective effects attributed to this compound and suggest its use as chemopreventive agent in a future.
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