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Lipoic acid effects on glutamate and taurine concentrations in rat hippocampus after pilocarpine-induced seizures

Efeitos do ácido lipóico nas concentrações de glutamato e taurina no hipocampo de ratos após convulsões induzidas por pilocarpina

Abstracts

Pilocarpine-induced seizures can be mediated by increases in oxidative stress and by cerebral amino acid changes. The present research suggests that antioxidant compounds may afford some level of neuroprotection against the neurotoxicity of seizures in cellular level. The objective of the present study was to evaluate the lipoic acid (LA) effects in glutamate and taurine contents in rat hippocampus after pilocarpine-induced seizures. Wistar rats were treated intraperitoneally (i.p.) with 0.9% saline (Control), pilocarpine (400 mg/kg, Pilocarpine), LA (10 mg/kg, LA), and the association of LA (10 mg/kg) plus pilocarpine (400 mg/kg), that was injected 30 min before of administration of LA (LA plus pilocarpine). Animals were observed during 24 h. The amino acid concentrations were measured using high-performance liquid chromatograph (HPLC). In pilocarpine group, it was observed a significant increase in glutamate content (37%) and a decrease in taurine level (18%) in rat hippocampus, when compared to control group. Antioxidant pretreatment significantly reduced the glutamate level (28%) and augmented taurine content (32%) in rat hippocampus, when compared to pilocarpine group. Our findings strongly support amino acid changes in hippocampus during seizures induced by pilocarpine, and suggest that glutamate-induced brain damage plays a crucial role in pathogenic consequences of seizures, and imply that strong protective effect could be achieved using lipoic acid through the release or decrease in metabolization rate of taurine amino acid during seizures.

seizures; pilocarpine; amino acids; hippocampus; glutamate; taurine


As convulsões induzidas pela pilocarpina podem ser mediadas através do aumento do estresse oxidativo cerebral e das alterações na concentração dos aminoácidos. O presente estudo sugere que compostos antioxidantes podem produzir neuroproteção contra a neurotoxicidade em nível celular causada pelas convulsões. O objetivo deste estudo foi avaliar os efeitos do ácido lipóico (AL) no conteúdo de glutamato e taurina no hipocampo de ratos durante convulsões induzidas por pilocarpina. Ratos Wistar foram tratados por via intraperitoneal com solução salina 0,9% (controle), pilocarpina (400 mg/kg, pilocarpina), AL (10 mg/kg) e com a associação de AL (10 mg/kg); 30 min após com pilocarpina (400 mg/kg), que foi injetada 30 min após a administração de AL (AL + pilocarpina). Os animais foram observados durante 24 horas. As concentrações de aminoácidos foram determinadas por HPLC. No hipocampo dos ratos do grupo pilocarpina foi observado um aumento significativo de 37% na concentração de glutamato e uma diminuição de 18% no nível de taurina, quando comparado ao grupo controle. O pré-tratamento com o antioxidante reduziu significativamente o nível de glutamato em 28% e aumentou em 32% os níveis de taurina no hipocampo dos ratos, quando comparado ao grupo pilocarpina. Nossos resultados sugerem que ocorrem alterações na concentração dos aminoácidos no hipocampo de ratos durante as convulsões induzidas por pilocarpina, e que o glutamato pode desempenhar um papel crucial na fisiopatologia das convulsões, e que o efeito protetor poderia ser alcançado com pré-tratamento com ácido lipóico, provavelmente pelo aumento da liberação ou redução da taxa de metabolização dos aminoácidos durante as convulsões.

convulsões; pilocarpina; aminoácidos; hipocampo; glutamato; taurina


ARTICLE

Lipoic acid effects on glutamate and taurine concentrations in rat hippocampus after pilocarpine-induced seizures

Efeitos do ácido lipóico nas concentrações de glutamato e taurina no hipocampo de ratos após convulsões induzidas por pilocarpina

Pauline Sousa dos SantosI; Lidianne Mayra Lopes CampêloI; Rizângela Lyne Mendes de FreitasII; Chistiane Mendes FeitosaI; Gláucio Barros SaldanhaII; Rivelilson Mendes de FreitasI

IPrograma de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Tecnologia Farmacêutica, Laboratório de Pesquisa em Neuroquímica Experimental, Universidade Federal do Piauí (NTF/LAPNEX/UFPI), Teresina PI, Brazil

IILaboratório de Patologia Clínica, Fortaleza CE, Brazil

Correspondence Correspondence: Rivelilson Mendes de Freitas Curso de Farmácia / Centro de Ciências da Saúde do Campus Universitário Ministro Petrônio Portella 64049-550 Teresina PI - Brasil E-mail: rivelilson@pq.cnpq.br

ABSTRACT

Pilocarpine-induced seizures can be mediated by increases in oxidative stress and by cerebral amino acid changes. The present research suggests that antioxidant compounds may afford some level of neuroprotection against the neurotoxicity of seizures in cellular level. The objective of the present study was to evaluate the lipoic acid (LA) effects in glutamate and taurine contents in rat hippocampus after pilocarpine-induced seizures. Wistar rats were treated intraperitoneally (i.p.) with 0.9% saline (Control), pilocarpine (400 mg/kg, Pilocarpine), LA (10 mg/kg, LA), and the association of LA (10 mg/kg) plus pilocarpine (400 mg/kg), that was injected 30 min before of administration of LA (LA plus pilocarpine). Animals were observed during 24 h. The amino acid concentrations were measured using high-performance liquid chromatograph (HPLC). In pilocarpine group, it was observed a significant increase in glutamate content (37%) and a decrease in taurine level (18%) in rat hippocampus, when compared to control group. Antioxidant pretreatment significantly reduced the glutamate level (28%) and augmented taurine content (32%) in rat hippocampus, when compared to pilocarpine group. Our findings strongly support amino acid changes in hippocampus during seizures induced by pilocarpine, and suggest that glutamate-induced brain damage plays a crucial role in pathogenic consequences of seizures, and imply that strong protective effect could be achieved using lipoic acid through the release or decrease in metabolization rate of taurine amino acid during seizures.

Key words: seizures, pilocarpine, amino acids, hippocampus, glutamate, taurine.

RESUMO

As convulsões induzidas pela pilocarpina podem ser mediadas através do aumento do estresse oxidativo cerebral e das alterações na concentração dos aminoácidos. O presente estudo sugere que compostos antioxidantes podem produzir neuroproteção contra a neurotoxicidade em nível celular causada pelas convulsões. O objetivo deste estudo foi avaliar os efeitos do ácido lipóico (AL) no conteúdo de glutamato e taurina no hipocampo de ratos durante convulsões induzidas por pilocarpina. Ratos Wistar foram tratados por via intraperitoneal com solução salina 0,9% (controle), pilocarpina (400 mg/kg, pilocarpina), AL (10 mg/kg) e com a associação de AL (10 mg/kg); 30 min após com pilocarpina (400 mg/kg), que foi injetada 30 min após a administração de AL (AL + pilocarpina). Os animais foram observados durante 24 horas. As concentrações de aminoácidos foram determinadas por HPLC. No hipocampo dos ratos do grupo pilocarpina foi observado um aumento significativo de 37% na concentração de glutamato e uma diminuição de 18% no nível de taurina, quando comparado ao grupo controle. O pré-tratamento com o antioxidante reduziu significativamente o nível de glutamato em 28% e aumentou em 32% os níveis de taurina no hipocampo dos ratos, quando comparado ao grupo pilocarpina. Nossos resultados sugerem que ocorrem alterações na concentração dos aminoácidos no hipocampo de ratos durante as convulsões induzidas por pilocarpina, e que o glutamato pode desempenhar um papel crucial na fisiopatologia das convulsões, e que o efeito protetor poderia ser alcançado com pré-tratamento com ácido lipóico, provavelmente pelo aumento da liberação ou redução da taxa de metabolização dos aminoácidos durante as convulsões.

Palavras-chave: convulsões, pilocarpina, aminoácidos, hipocampo, glutamato, taurina.

Systemic injection of pilocarpine in rodents is an experimental model largely used to study the pathophysiology of seizures and to identify potential therapeutic agents for treatment of epilepsy. This seizures model demonstrates the potent pro-convulsant effect of pilocarpine and reproduces the behavioral, electroencephalographic and neurochemical alterations associated with seizures that are similar to those of temporal lobe epilepsy in humans1-3. Other researches suggest permanent changes in the concentration of the brain neurotransmitters during seizures and status epilepticus (SE) induced by pilocarpine4-9. An increase in dopamine level, a decrease in serotonin (5-HT) content, and also an excessive increase in concentration of 3,4-hydroxyphenylacetic acid (DOPAC) may occur in hippocampus and frontal cortex of adult rats during SE induced by pilocarpine10.

Studies have demonstrated that the installation of seizures requires cholinergic stimulation, but some other neurotransmitter systems appear to be responsible for propagation and maintenance of seizures11. Although changes in concentrations of brain amino acid during seizures might be either a cause or a consequence of the ongoing epileptic activity, we have investigated the levels of glutamate and tyrosine during pilocarpine-induced seizures, as a first step in determining the possible role of these neurotransmitters during the propagation and maintenance of limbic seizures.

The amino acids are involved in several physiological events, including brain development and ageing, in physiological integration among brain structures, and in the processes of learning and memory12. Neurotransmitter systems alterations can be implicated in seizures due an increase in their oxidative metabolism or by a decrease in their syntheses and/or release7,9. Epileptic activity can occur through a wide range of local neurochemical changes that affects several neurotransmitters, such as adenosine, norepinephrine, dopamine, 5-HT, glutamate, γ-amino butyric (GABA), aspartate, tyrosine, taurine and glutamine11,13-15.

Studies have demonstrated changes in mobilization rate of amino acid in hippocampus of rats during seizures13. In addition, little is known about the effects of antioxidant compounds in amino acid concentration in hippocampus of adult rats after seizures pilocarpine-induced. Despite the fact that several studies clearly indicate the importance of amino acids in epileptic phenomenon16,17, it is important to verify the effects of antioxidant drugs in cerebral amino acid levels during seizures. Based on these facts, there is an increasing evidence of the involvement of augmented glutamatergic transmission during seizures pilocarpine-induced. We have decided to investigate the effects of lipoic acid in glutamate and taurine concentrations in the hippocampus of adult rats after seizures pilocarpine- induced.

METHOD

Male Wistar rats (250-280g; 2-month-old) were used. Animals were housed in cages with free access to food and water and were kept with standard light-dark cycle (lights on at 07:00h a.m.). The experimental protocols were approved by the Faculty Ethics Committee. The experiments were performed according to the Guide for the care and use of laboratory of the US Department of Health and Human Services, Washington, DC (1985). All doses are expressed in milligrams per kilogram and were administered in a volume of 10 ml/kg injected intraperitoneally (i.p.).

In a set of experiments, the animals were divided in four groups and treated with lipoic acid (10 mg/kg, i.p., n=20) or 0.9% saline (i.p., n=20) and 30 min later, they received pilocarpine hydrochloride (400 mg/kg, i.p.). The treatments previously described represent the LA plus pilocarpine and pilocarpine groups, respectively. The third and fourth groups received alone 0.9% saline (i.p., n=20, control group) and lipoic acid (10 mg/kg, i.p., n=20, LA group), respectively. After the treatments the animals were observed during 24 h to determinations of behavioral changes, such as appearance of peripheral cholinergic reactions, such as miosis, piloerection, chromodacryorrhea, diarrhea, masticatory and stereotyped movements, seizures, status epilepticus and mortality rate. The survivors were killed by decapitation and their brains dissected on ice to remove hippocampus to amino acid determinations. The pilocarpine group was constituted by those rats that presented seizures; SE for a period longer than 30 min and that did not died during 24 h.

Immediately after rats were decapitated, the hippocampus, striatum and frontal cortex were removed on an ice-chilled plate, weighed, and stored at -120ºC. Tissues were ultrasonically homogenized in a 0.1 M solution of HClO4 containing 0.02% HSER (10 µg/ml) (as internal standard for amino acids) in a proportion of 15 µg solution for each milligram wet tissue. The samples were then centrifuged at 11.000×g at 4ºC for 40 min. the supernatant as filtered and injected into high-performance liquid chromatograph (HPLC) system. HPLC system was used simultaneously to analyze amino acids18.

Amino acid determination was performed after a pre-column derivatization procedure. The reagent was prepared by dissolving 27 mg OPA in 1 ml methanol followed by 5 µl mercaptoethanol (BME) and 9 ml 0.1M sodium tetraborate (pH 9.3). This OPA/BME stock solution was diluted threefold in tetraborate just before the use. Precolumn amino acid derivatization was accomplished by mixing 50 µl samples with 100 µl working OPA/BME reagent at exactly 2 min before its injection into the analytical column.

Gradient HPLC system, used to analyze amino acids, was composed of two pumps linked to a programmable gradient controller (Milton Roy), coupled with an electrochemical detector (potential +0.9V; Spark Holland). A rheodyne injector with a 20 µl loop was connected to a Lichorospher 100 RP-18, 5 µm (125×4mm) columns, with a flow rate of 1ml/ min. Amino acids were eluted with a gradient solvent system as described by Joseph and Davies19.

Mobile phase A contained sodium phosphate 0.05M (pH 5.5) buffer plus 0.03% NaCl/methanol 20%. Mobile phase B consisted of sodium phosphate 0.05M (pH 5.5) buffer plus 0.03% NaCl/methanol 80%. Standard mixtures of amino acids were injected at the beginning and of each set of six analyses to control the performance of system. Amino acid recoveries were made after addition of 200 µg of taurine and glutamate to 10 ml of 0.1 M of HClO4 containing 0.02% of Na2S2O5 and 100 µg of HSER. Tissues were then homogenized in this solution, and amino acids were quantified. The recovery of amounts added was determined by subtracting the amount originally in the tissue. The values obtained were expressed as mmol/g tissue wet weight.

Results are expressed as means ±S.E.M. for the number of experiments, with all measurements performed in duplicate. The Student-Newman-Keuls test was used for multiple comparisons of means of two groups of data. Differences were considered significant at p<0.05. Differences in experimental groups were determined by two-tailed analysis of variance.

RESULTS

According to our previous studies3,20, immediately after pilocarpine administration, animals persistently had behavioral changes, including initial akinesia, ataxic lurching, peripheral cholinergic signs (miosis, piloerection, chomodacryorrhea, diarrhea and masticatory automatisms), stereotyped movements (continuous sniffing, paw licking, rearing and wet dog shakes that persisted for 10-15 min), clonic movements of forelimbs, head bobbing and tremors. These behavioral changes progressed to motor limbic seizures as previously described by Turski et al.3. Pilocarpine induced the first seizure at 35.00±0.70 min. Limbic seizures persisted for 30-50 min evolving to SE in all rats. In the latter experiments, 60% of animals died during the 24 h observation period. The animals pre-treated with lipoic acid 30 min before with pilocarpine (LA plus pilocarpine) developed cholinergic reactions, stereotyped movements and tremors; 10% (02/20) had seizures, 10% (02/20) built up to status epilepticus and no one animal died. Table shows that lipoic acid (10 mg/kg) administration before pilocarpine treatment reduced by 50% the percentage of animals that seized (p<0.0001), increased latency (154%) to the first seizure (89.00±1.95 min) (p<0.0001) and increased (60%) the survival (p<0.0001) when compared to the pilocarpine only group. None of the control animals (saline or lipoic acid) showed seizures.

Effects of lipoic acid in glutamate and taurine concentrations in hippocampus of adult rats during seizures induced by pilocarpine are presented in Figures 1 and 2. Glutamate level was markedly increased in pilocarpine group, when compared with corresponding values for the control group [T(14)=3.860; p<0.0017]. During acute phase of seizures induced by pilocarpine, it was observed a significant (18%) decrease in taurine content [T(14)=2.416; p<0.0300], when compared with corresponding values for the control group.



Post hoc comparison of means indicated a significant decreases of 28% in hippocampal glutamate level [T(12)=3.277; p<0.0066] of rats pretreated with lipoic acid, when compared with the pilocarpine group. Post hoc comparison of means indicated a significant (32%) increase in hippocampal taurine content of rats pretreated with lipoic acid [T(12)=4.876; p<0.0004], when compared to pilocarpine group.

DISCUSSION

Changes in amino acid brain concentration are, of course, crude approximations of changes which may be occurring at the synaptic level. Furthermore, some of these amino acids have metabolic roles in brain, in addition to their as neurotransmitter functions6. The changes we have found do appear to be secondary to any general derangement produced by seizures in amino acid metabolism, for several reasons. We observed an increase in glutamate and a decrease in taurine in hippocampus of rats during seizures.

Several amino acids have been associated with the mechanism of pilocarpine-induced seizures18. Significant differences in tyrosine and glutamate contents were evident in hippocampus during the installation of seizures induced by pilocarpine. Other studies have shown that during the chronic phase of pilocarpine-induced seizures, the GABA, dopamine and glutamine levels in hippocampus were increased, suggesting that a neuronal release may occur and under the same conditions, decreased aspartate and glutamate levels18 were verified.

Our work showed that hippocampal glutamate and taurine levels, increased and decreased during acute phase of seizures, respectively, suggesting that these amino acids can have a important function during installation of seizures. Therefore, it is likely that the amino acids studied can be interconnected in epileptic activity. In support to this finding, an increase in hippocampal glutamate content was observed by Cavalheiro et al.17, suggesting an idea of decreases in oxidative metabolism and cellular death observed in hippocampal neurons during the chronic phase of seizures in rats. On the other hand, the taurine level in hippocampus of rats was not altered during chronic phase of seizures induced by pilocarpine. In contrast of these findings, Yablonsky-Alter et al.21 reported an increase in the release of neuroprotective amino acid taurine in the striatum rats treated with cocaine.

In the present study we have examined whether the pretreatment with lipoic acid can reverse the alterations observed in glutamate and taurine in hippocampus of adult rats after seizures induced by pilocarpine. Generation of reactive oxygen species is currently viewed as one of the process through which epileptic activity exert their deleterious effects on brain22. These reactive oxygen species in the absence of an efficient cellular defence mechanism cause peroxidation of membrane poly unsaturated fatty acids. Brain is particularly susceptible to peroxidation due to simultaneous presence of high levels of poly unsaturated fatty acids and iron23, which is the target of free radical damage. It has been demonstrated that seizures induced by pilocarpine produces changes in oxidative metabolism and interacts with glutamatergic receptors to produced part of its stimulatory action on the central nervous system24-27. The fall in glutamate content, after pretreatment with lipoic acid, is most readily explained as a consequence of inhibiting their release or increasing their metabolization28-30. Moreover, the lipoic acid can reduce the metabolization rate and/or augment the release and syntheses of neuroprotective taurine, suggesting a protective action of this amino acid against the excitotoxicity mediated by glutamate during seizures.

Our results clearly show that the cholinergic receptors are stimulated by pilocarpine administration during installation of seizures; moreover, several neurotransmitter systems can be involved also in initiation and in propagation and maintenance processes during establishment of seizures. Therefore, lipoic acid represents a possible neuroprotective agent against the risks of acute phase of seizures induced by pilocarpine. Results suggest the involvement in lipoic acid action mechanism of the neuroprotective amino acid (taurine) during seizures induced by pilocarpine in rats. Lipoic acid could provide further insights for neuroprotection and may lead to the development of effective therapeutic strategies against epilepsy in humans.

ACKNOWLEDGEMENTS - We would like to thank Stenio Gardel Maia for her technical assistance.

Received 8 September 2010

Received in final for 12 November 2010

Accepted 19 November 2010

Support This work was supported in part by grants from the Brazilian National Research Council (CNPq), Brazil. R.M.F and C.M.F. are fellows from CNPq

  • 1. Freitas RM. The evaluation of effects of lipoic acid on the lipid peroxidation, nitrite formation and antioxidant enzymes in the hippocampus of rats after pilocarpine-induced seizures. Neurosci Lett 2009;455:140-144.
  • 2. Freitas RM, Sousa FCF, Vasconcelos SMM, Viana GSB, Fonteles MMF. Pilocarpine-induced seizures in adult rats: lipid peroxidation level, nitrite formation, GABAergic and glutamatergic receptor alterations in the hippocampus, striatum and frontal cortex. Pharmacol Biochem Behav 2004;78: 327-332.
  • 3. Turski WA, Cavalheiro EA, Schwarz M, Czuczwar SJ, Kleinronk Z, Turski L. Limbic seizures produced by pilocarpine in rats: behavioural, eletroencephalographic and neuropathological study. Behav Brain Res 1983;9:315-336.
  • 4. Ferreira PMP, Militão GCG, Freitas RM. Lipoic acid effects on lipid peroxidation level, superoxide dismutase activity and monoamines concentration in rat hippocampus. Neurosci Lett 2009;464:131-134.
  • 5. Freitas RM, Souza FCF, Vasconcelos SMM, Viana GSB, Fonteles MMF. Oxidative stress in the hippocampus after status epilepticus in rats. FEBS J 2005;272:1307-1312.
  • 6. Tomé AR, Ferreira PMP, Freitas RM. Inhibitory action of antioxidants (ascorbic acid or alfa-tocopherol) on seizures and bran damage induced by pilocarpine in rats. Arq Neuropsiquiatr 2010;68:355-361.
  • 7. Santos IMS, Freitas RLM, Saldanha GB, Tomé AR, Jordán J, Freitas RM. Alterations on monoamines concentration in rat hippocampus produced by lipoic acid. Arq Neuropsiquiatr 2010;68:362-366.
  • 8. Freitas RM, Souza FCF, Vasconcelos SMM, Viana GSB, Fonteles MMF. Acute alterations of neurotransmitters levels in striatum of young rat after pilocarpine-induced status epilepticus. Arq Neuropsiquiatr 2003;61:430-433.
  • 9. Li Z, Piao F, Liu S, et al. Preventive effects of taurine and vitamin C on renal DNA damage of mice exposed to arsenic. J Occup Health 2009;51:169-172.
  • 10. Freitas RM, Vasconcelos SMM, Souza FCF, Viana GSB, Fonteles MMF. Monoamine levels after pilocarpine-induced status epilepticus in hippocampus and frontal cortex of Wistar rats. Neurosci Lett 2004;370:196-200.
  • 11. Walton NY, Gunawan S, Treiamn D. Brain amino acid concentration changes during status epilepticus induced buy lithium and pilocarpine. Exp Neurol 1990;108:61-70.
  • 12. Ozawa S, Kamiya H, Tsuzuki K. Glutamate receptors in the mammalian central nervous system. Prog Neurobiol 1998;54:581-618.
  • 13. Costa MS, Rocha JBT, Perosa SR, Cavalheiro EA, Naffah-Mazzacoratti MG. Pilocarpine-induced status epilepticus increases glutamate release in rat hippocampal synaptosomes. Neurosci Lett 2004;356:1-4.
  • 14. De Lorenzo RJ, Kochan LD, Churn SB. Chronic inhibition of Ca+2 calmodulin kinase II activity in the pilocarpine model of epilepsy. Brain Res 2000;75:66-77.
  • 15. Montiel T, Camacho A, Estrada-Sanchez AM, Massieu L. Differential effects of the substrate inhibitor l-trans-pyrrolidine-2,4-dicarboxylate (PDC) and the non substrate inhibitor dl-threo-beta-benzyloxyaspartate (dl-TBOA) of glutamate transporters on neuronal damage and extracellular amino acid levels in rat brain in vivo. Neuroscience 2005;133:667-678.
  • 16. Ortiz JG, Moshé SL, Sperber EF, Velisek L, Ferchmin P, Claudio OI. Plasticity of excitatory amino acid transporters in experimental epilepsy. Epilepsia 2000;41:104-110.
  • 17. Cavalheiro EA, Leite JP, Bortolotto ZA, Turski WA, Ikonomidou C, Turski L. Long-term effects of pilocarpine in rats: structural damage of the brain triggers kindling and spontaneous recurrent seizures. Epilepsia 1991;32: 778-782.
  • 18. Cavalheiro EA, Fernandes MJ, Turski L, Naffah-Mazzacoratti MG. Spontaneous recurrent seizures in rats: amino acid ad monoamine determination in the hippocampus. Epilepsia 1994;35:1-11.
  • 19. Joseph MH, Davies P. Electrochemical activity of o-phthalaldehyde-mercaptoethanol derivatives of amino acids: Application to high-performance liquid chromatographic determination of amino acids in plasma and other biological materials. J Chromatogr Biomed Appl 1983;277:125-136.
  • 20. Marinho MMF, Sousa FCF, Bruin VMS, Vale MR, Viana GSB. Effects of lithium, alone or associated with pilocarpine, on muscarinic and dopaminergic receptors and on phosphoinositide metabolism in rat hippocampus and striatum. Neurochem Int 1998;33:299-306.
  • 21. Yablonsky-Alter E, Agovic MS, Gashi E, Lidsky TI, Friedman E, Banerjee SP. Cocaine challenge enhances release of neuroprotective amino acid taurine in the striatum of chronic cocaine treated rats: a microdialysis study. Brain Res Bull 2009;20:72-79.
  • 22. Castagne V, Gastschi M, Lefevre K, Posada A, Clarke PGH. Relationship between neuronal death and cellular redox status, focus on the developing nervous system. Prog Neurophysiol 1999;59:397-423.
  • 23. Halliwell B, Gutteridge JMC. Free radicals in biology and medicine. London: Oxford Science Publications; 1999.
  • 24. Dymond AD, Crandall PH. Oxygen availability and blood flow in the temporal lobes during spontaneous epileptic seizures in men. Brain Res 1976;102:191-196.
  • 25. Khan GM, Smolders I, Ebinger G, Michotte Y. Anticonvulsant effect and neurotransmitter modulation of focal and systemic 2-chloroadenosine against the development of pilocarpine-induced seizure. Neuropharmacology 2000;39:2418-2432.
  • 26. McCord J. Superoxide radical: controversies, contradiction and paradoxes. Proc Soc Exp Biol Med 1989;209:112-117.
  • 27. Militão GCG, Ferreira PMP, Freitas RM. Effects of lipoic acid on oxidative stress in rat striatum after pilocarpine-induced seizures. Neurochem Int 2009;56:16-20.
  • 28. Jammoul F, Wang Q, Nabbout R, et al. Taurine deficiency is a cause of vigabatrin-induced retinal phototoxicity. Ann Neurol 2009;65:98-107.
  • 29. Harris RA, Joshi M, Jeoung NH, Obayashi M. Overview of the molecular and biochemical basis of branched-chain amino acid catabolism. J Nutr 2005; 135(Suppl):S1527-S1530.
  • 30. Maczurek A, Hager J, Kenklies M, et al. Lipoic acid as an anti-inflammatory and neuroprotective treatment for Alzheimer's disease. Adv Drug Deliver Rev 2008;60:1463-1470.
  • Correspondence:

    Rivelilson Mendes de Freitas
    Curso de Farmácia / Centro de Ciências da Saúde do Campus Universitário Ministro Petrônio Portella
    64049-550 Teresina PI - Brasil
    E-mail:
  • Publication Dates

    • Publication in this collection
      20 May 2011
    • Date of issue
      2011

    History

    • Accepted
      19 Nov 2010
    • Reviewed
      12 Nov 2010
    • Received
      08 Sept 2010
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