RESUMO
Neoflavonoids, which are classified as 4-arylcoumarin (neoflavone), 3,4-dihydro-4-arylcoumarin and neoflavene, have been the subject of a number of studies with respect to their therapeutic potential and, despite promising in vitro, ex vivo and in vivo pharmacological activities, there is a lack of studies demonstrating their toxicological properties. Therefore, this study aims to evaluate the acute (14 days) and repeated-dose (28 days) toxicity of synthetic neoflavonoid 7-acetoxy-4-aryl-3,4-dihydrocoumarin in Swiss mice through parameters related to changes in body weight, food and water intake, hematological and biochemical parameters. Toxicity studies using acute doses (300 and 2000â¯mg/kg) and repeated doses (250, 500 and 1000â¯mg/kg) orally were carried out as per Organization for Economic Co-operation and Development (OECD) guidelines 423 and 407, respectively. Based on the results of this study, treatment with 7-acetoxy-4-aryl-3,4-dihydrocoumarin was found to not cause clinical adverse symptoms and mortality in any animal used in the acute and repeated-dose toxicity study. In addition, no significant changes were observed in body weight and internal organs, food and water intake, hematological and biochemical parameters, compared to control group. Therefore, these results provide an initial understanding regarding the toxicity profile of 7-acetoxy-4-aryl-3,4-dihydrocoumarin, which can be considered a neoflavonoid with toxicity seen at doses higher than 2000â¯mg/kg in Swiss mice.
Assuntos
Cumarínicos/toxicidade , Animais , Artemia/efeitos dos fármacos , Feminino , Masculino , Camundongos , Testes de Toxicidade Aguda , Testes de Toxicidade SubagudaRESUMO
The study investigated the prevalence of legal and/or illegal drugs among students enrolled in Health Sciences Courses (HSC) at a university located in the Quixadá municipality, State of Ceará. The study was conducted through a questionnaire administered to 345 HSC students. The resulting profile was of single white females, ages 16-20 years old, unemployed, with a household income of 2-4 minimum wage salaries. The vast majority does not use any legal or illegal drugs. However, 39 and 16% use alcohol and cocaine, especially for the high, and mainly because of peer pressure during social events. The majority of the students self-medicate. The study suggests that alcohol and drug use within this population is alarming and that new surveys need to be conducted.
O trabalho investigou a prevalência do uso de drogas lícitas e/ou ilícitas entre os universitários dos Cursos de Ciências da Saúde de uma instituição de ensino superior do município de Quixadá, Ceará. O estudo foi realizado por meio de um questionário aplicado entre 345 universitários dos Cursos de Ciências da Saúde em questão. O perfil dos universitários estudados é de mulheres na faixa etária de 16 a 20 anos, solteiras, brancas, que não exerciam atividade remunerada, com renda familiar de 2 a 4 salários-mínimos. A grande maioria não fazia uso de nenhuma droga lícita ou ilícita. Entretanto, entre 39 e 16% fazia uso do álcool e da cocaína, respectivamente, devido, em especial, à sensação de alegria, e, principalmente, pela influência dos amigos em eventos sociais. A maioria dos universitários pratica automedicação. O estudo realizado sugere que o problema de uso de drogas e álcool nessa população é preocupante e novos levantamentos precisam ser realizados.
El trabajo investigó la superioridad del uso de drogas lícitas y/o ilícitas entre los universitarios de los Cursos de Ciencias de la Salud (CCS) de una institución de enseñanza superiora del municipio de Quixadá, Ceará. El estudio fue realizado por medio de un cuestionario aplicado entre 345 universitarios del CCS en cuestión. El perfil de los universitarios estudiados es de mujeres con banda etaria de 16 a 20 años, solteras, blancas, que no ejercen actividad remunerada con renta familiar de 2 a 4 salarios mínimos. La grande mayoría no hace uso de ninguna droga lícita o ilícita. Mientras, 39 y 16% hace uso del alcohol y de la cocaína, respectivamente, debido en especial a la sensación de alegría, y principalmente por la influencia de los amigos en eventos sociales. La mayoría de los universitarios practica automedicación. El estudio realizado sugiere que el problema de uso de drogas y alcohol en esa población es preocupante y nuevos levantamientos necesitan ser realizados.
Assuntos
Humanos , Masculino , Feminino , Estudantes , Universidades , Drogas Ilícitas , Estudos Transversais , Transtornos Relacionados ao Uso de Substâncias , Alcoolismo/epidemiologia , Consumo de Álcool na FaculdadeRESUMO
Alpha-tocopherol has numerous nonenzymatic actions and is a powerful liposoluble antioxidant. The objective of the present study was to evaluate the neuroprotective effects of alpha-tocopherol in rats against oxidative stress caused by pilocarpine-induced seizures. Wistar rats were intraperitoneally treated with 0.9% saline (control group), alpha-tocopherol (200 mg/kg, alpha-tocopherol group), pilocarpine (400 mg/kg, pilocarpine group), or the combination of alpha-tocopherol (200 mg/kg) and pilocarpine (400 mg/kg, i.p.; alpha-tocopherol plus pilocarpine group). After the treatments, all groups were observed for 24 h. The superoxide dismutase (Mn-SOD) and catalase activities, lipid peroxidation and nitrite concentrations were measured using spectrophotometrically methods. To clarify the mechanism of alpha-tocopherol on oxidative stress in pilocarpine model, Western blot analysis of Mn-SOD and catalase in rat striatum were performed. In the pilocarpine group, rats showed a significant increase in lipid peroxidation and nitrite levels. However, there were no alterations on Mn-SOD activity. On the other hand, the catalase activity augmented in pilocarpine group. In the alpha-tocopherol and pilocarpine co-administered rats, antioxidant treatment significantly reduced the lipid peroxidation level and nitrite content and increased the Mn-SOD and catalase activities in rat striatum after seizures. Pilocarpine, alpha-tocopherol plus pilocarpine and alpha-tocopherol groups did not affect of the Mn-SOD and catalase mRNA or protein levels. Our findings strongly support the hypothesis that oxidative stress occurs in striatum during pilocarpine-induced seizures, indicating that brain damage induced by the oxidative process plays a crucial role in seizures pathogenic consequences, which implies that strong protective effect could be achieved using alpha-tocopherol.
Assuntos
Neostriado/efeitos dos fármacos , Neostriado/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Pilocarpina/efeitos adversos , Convulsões/induzido quimicamente , Convulsões/metabolismo , alfa-Tocoferol/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Catalase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Neostriado/patologia , Nitritos/metabolismo , Ratos , Ratos Wistar , Convulsões/tratamento farmacológico , Convulsões/patologia , Superóxido Dismutase/metabolismo , Fatores de Tempo , alfa-Tocoferol/uso terapêuticoRESUMO
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.
Assuntos
Antioxidantes/farmacologia , Ácido Glutâmico/metabolismo , Hipocampo/efeitos dos fármacos , Convulsões/metabolismo , Taurina/metabolismo , Ácido Tióctico/farmacologia , Animais , Cromatografia Líquida de Alta Pressão , Hipocampo/química , Masculino , Pilocarpina , Ratos , Ratos Wistar , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológicoRESUMO
The antioxidant and antinociceptive activities of Citrus limon essential oil (EO) were assessed in mice or in vitro tests. EO possesses a strong antioxidant potential according to the scavenging assays. Moreover, it presented scavenger activity against all in vitro tests. Orally, EO (50, 100, and 150 mg/kg) significantly reduced the number of writhes, and, at highest doses, it reduced the number of paw licks. Whereas naloxone antagonized the antinociceptive action of EO (highest doses), this suggested, at least, the participation of the opioid system. Further studies currently in progress will enable us to understand the action mechanisms of EO.
Assuntos
Analgésicos/antagonistas & inibidores , Antioxidantes/farmacologia , Citrus , Sequestradores de Radicais Livres/farmacologia , Óleos Voláteis/administração & dosagem , Dor/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Administração Oral , Analgésicos/análise , Animais , Antioxidantes/análise , Citrus/química , Modelos Animais de Doenças , Sequestradores de Radicais Livres/análise , Masculino , Camundongos , Naloxona , Óleos Voláteis/isolamento & purificação , Medição da Dor , Extratos Vegetais/análise , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , RutaceaeRESUMO
This study was aimed at investigating the anticonvulsant activity of lipoic acid (LA) against pilocarpine-induced seizures as well as the effects of this metabolic antioxidant on the hippocampal extracellular concentrations of amino acid neurotransmitters glutamate, aspartate, glycine and glutamate and γ-aminobutyric acid (GABA). In vivo microdialysis demonstrated that an intraperitoneal administration of pilocarpine induced a pronounced increment of hippocampal glutamate and aspartate concentrations, whereas no significant change was observed in the levels of glycine or GABA. LA (10, 20 or 30 mg/kg) pretreatment completely blocked pilocarpine-evoked increases in extracellular glutamate and aspartate concentrations. Significant reductions in hippocampal GABA and glycine concentrations were also observed although not as pronounced as those shown by glutamate and aspartate. Based on the finding that LA protected rats against pilocarpine-induced seizures, it could be suggested that the reduction in inhibitory amino acid neurotransmitters levels was comparatively minor and offset by a more pronounced reduction in glutamate and aspartate extracellular concentrations. Therefore, the fact that LA could drastically reduce pilocarpine-induced increases in glutamate and aspartate should account, at least partly, for its anticonvulsant activity observed in pilocarpine-induced seizure in rats.
Assuntos
Aminoácidos Excitatórios/líquido cefalorraquidiano , Hipocampo/metabolismo , Pilocarpina/farmacologia , Convulsões/metabolismo , Ácido Tióctico/farmacologia , Animais , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Ácido Aspártico/líquido cefalorraquidiano , Diálise/métodos , Ácido Glutâmico/líquido cefalorraquidiano , Glicina/líquido cefalorraquidiano , Hipocampo/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Convulsões/induzido quimicamente , Convulsões/mortalidade , Convulsões/fisiopatologia , Convulsões/prevenção & controle , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/metabolismo , Estado Epiléptico/mortalidade , Estado Epiléptico/fisiopatologia , Estado Epiléptico/prevenção & controle , Análise de Sobrevida , Ácido Tióctico/uso terapêutico , Ácido gama-Aminobutírico/líquido cefalorraquidianoRESUMO
Alpha-lipoic acid has some neuroprotective properties, but this action has not been investigated in models of epilepsy. The aim of the present study was to investigate the protective efficacy of α-lipoic acid (lipoic acid) against pilocarpine-induced cell death through the caspase-dependent or -independent mitochondrial apoptotic pathways. Wistar rats were injected intraperitoneally with 0.9% saline (control group), pilocarpine (400 mg/kg, pilocarpine group) alone, or α-lipoic acid (20 mg/kg) in association with pilocarpine (400 mg/kg) 30 min before administration of α-lipoic acid. After the treatments all groups were observed for 24 h. Cell death was reduced in lipoic acid-treated rats. Cytosolic translocation of cytochrome c and subsequent activation of caspase-3 were reduced by lipoic acid treatment. AIF nuclear translocation and subsequent large-scale DNA fragmentation were also decreased in lipoic acid-treated rats. Our study suggests that lipoic acid inhibits both caspase-dependent and -independent apoptotic pathways and may be neuroprotective against hippocampal damage during pilocarpine-induced seizures.
Assuntos
Caspases/metabolismo , Morte Celular/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Pilocarpina/toxicidade , Convulsões/prevenção & controle , Ácido Tióctico/farmacologia , Animais , Western Blotting , Hipocampo/enzimologia , Hipocampo/fisiopatologia , Masculino , Ratos , Ratos Wistar , Convulsões/induzido quimicamente , Convulsões/patologiaRESUMO
The objective of the study was to evaluate the caffeic acid (CA) effects against the oxidative stress (OS) observed during seizures. Wistar rats were intraperitoneally treated with either 0.9% saline (control), CA (4 mg/kg), pilocarpine (400 mg/kg, pilocarpine group), or the association of CA (4 mg/kg) plus pilocarpine (400 mg/kg). The thiobarbituric-acid-reacting substances and the hippocampal nitrite content were significantly increased (89 and 94%, respectively) in pilocarpine group when compared with control. There were marked decreases in lipid peroxidation level (43%) and nitrite content (45%) in CA group when compared with pilocarpine group. There were no marked alterations in superoxide dismutase (SOD) and catalase (CAT) activities in pilocarpine group; however, the SOD and CAT activities were significantly increased (35 and 51%, respectively) after CA pretreatment. Our findings strongly support the hypothesis that OS was indeed generated in hippocampus. CA pretreatment can reduces the OS produced by seizures.
Assuntos
Ácidos Cafeicos/farmacologia , Epilepsia/induzido quimicamente , Epilepsia/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Modelos Animais de Doenças , Epilepsia/fisiopatologia , Masculino , Degeneração Neural/tratamento farmacológico , Degeneração Neural/metabolismo , Degeneração Neural/fisiopatologia , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/fisiologia , Ratos , Ratos WistarRESUMO
In the present study we investigated the effects of lipoic acid (LA) on acetylcholinesterase (AChE), glutathione peroxidase (GPx) and Na+, K+-ATPase activities in rat hippocampus during seizures. Wistar rats were treated with 0.9% saline (i.p., control group), lipoic acid (20 mg/kg, i.p., LA group), pilocarpine (400 mg/kg, i.p., P400 group), and the association of pilocarpine (400 mg/kg, i.p.) plus LA (20 mg/kg, i.p.), 30 min before of administration of P400 (LA plus P400 group). After the treatments all groups were observed for 1 h. In P400 group, there was a significant increase in GPx activity as well as a decrease in AChE and Na+, K+-ATPase activities after seizures. In turn, LA plus P400 abolished the appearance of seizures and reversed the decreased in AChE and Na+, K+-ATPase activities produced by seizures, when compared to the P400 seizing group. The results from the present study demonstrate that preadministration of LA abolished seizure episodes induced by pilocarpine in rat, probably by increasing AChE and Na+, K+-ATPase activities in rat hippocampus.
Assuntos
Acetilcolinesterase/metabolismo , Antioxidantes/farmacologia , Glutationa Peroxidase/metabolismo , Hipocampo/enzimologia , Convulsões/enzimologia , ATPase Trocadora de Sódio-Potássio/metabolismo , Ácido Tióctico/farmacologia , Animais , Hipocampo/efeitos dos fármacos , Masculino , Pilocarpina , Ratos , Ratos Wistar , Convulsões/induzido quimicamenteRESUMO
In the present study we investigated the effects of lipoic acid (LA) on acetylcholinesterase (AChE), glutathione peroxidase (GPx) and Na+, K+-ATPase activities in rat hippocampus during seizures. Wistar rats were treated with 0.9 percent saline (i.p., control group), lipoic acid (20 mg/kg, i.p., LA group), pilocarpine (400 mg/kg, i.p., P400 group), and the association of pilocarpine (400 mg/kg, i.p.) plus LA (20 mg/kg, i.p.), 30 min before of administration of P400 (LA plus P400 group). After the treatments all groups were observed for 1 h. In P400 group, there was a significant increase in GPx activity as well as a decrease in AChE and Na+, K+-ATPase activities after seizures. In turn, LA plus P400 abolished the appearance of seizures and reversed the decreased in AChE and Na+, K+-ATPase activities produced by seizures, when compared to the P400 seizing group. The results from the present study demonstrate that preadministration of LA abolished seizure episodes induced by pilocarpine in rat, probably by increasing AChE and Na+, K+-ATPase activities in rat hippocampus.
No presente estudo nós investigamos os efeitos do ácido lipóico (AL) sobre as atividades da acetilcolinesterase (AChE), da glutationa peroxidase (GPx) e da Na+, K+-ATPase no hipocampo de ratos durante crises convulsivas. Ratos Wistar foram tratados com solução salina a 0,9 por cento (i.p., grupo controle), ácido lipóico (20 mg/kg, i.p., grupo AL), pilocarpina (400 mg/kg, i.p., grupo P400), e a associação de AL (20 mg/kg, i.p.) com a pilocarpina (400 mg/kg, i.p.), 30 min antes da administração de pilocarpina (grupo AL + P400). Após os tratamentos todos os grupos foram observados durante 1 h. No grupo P400, houve um aumento significativo na atividade da GPx, assim como uma diminuição das atividades da AChE e Na+, K+-ATPase. Por sua vez, o pré-tratamento com AL aboliu o aparecimento de convulsões e reverteu a diminuição das atividades da AChE e da Na+, K+-ATPase causadas pelas convulsões, quando comparada com o grupo P400 sozinho. Os resultados do estudo demonstram que o pré-tratamento com AL aboliu os episódios de convulsão induzido pela pilocarpina em ratos, provavelmente por meio do aumento das atividades das enzimas AChE e Na+, K+-ATPase no hipocampo de ratos.
Assuntos
Animais , Masculino , Ratos , Acetilcolinesterase/metabolismo , Antioxidantes/farmacologia , Glutationa Peroxidase/metabolismo , Hipocampo/enzimologia , Convulsões/enzimologia , ATPase Trocadora de Sódio-Potássio/metabolismo , Ácido Tióctico/farmacologia , Hipocampo/efeitos dos fármacos , Pilocarpina , Ratos Wistar , Convulsões/induzido quimicamenteRESUMO
The purposes of the present study were to verify monoamines (dopamine (DA), norepinephrine (NE), serotonin (5-HT)), and their metabolites (3,4-hydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA)) contents in rat hippocampus after lipoic acid (LA) administration. Wistar rats were treated with 0.9% saline (i.p., control group) and LA (10, 20 or 30 mg/kg, i.p., LA10, LA20 and LA30 groups, respectively). After the treatments all groups were observed for 24 h. The NE and DA levels were increased only in 20 mg/kg dose of LA in rat hippocampus. Serotonin content and in their metabolite 5-HIAA levels was decreased in same dose of LA. On the other hand, in DOPAC and HVA levels did not show any significant change. The alterations in hippocampal monoamines can be suggested as a possible of brain mechanism of action from this antioxidant. The outcome of the study may have therapeutic implications in the treatment of neurodegenerative diseases.
Assuntos
Antioxidantes/farmacologia , Monoaminas Biogênicas/metabolismo , Hipocampo/efeitos dos fármacos , Ácido Tióctico/farmacologia , Animais , Hipocampo/metabolismo , Masculino , Ratos , Ratos WistarRESUMO
The purposes of the present study were to verify monoamines (dopamine (DA), norepinephrine (NE), serotonin (5-HT)), and their metabolites (3,4-hydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA)) contents in rat hippocampus after lipoic acid (LA) administration. Wistar rats were treated with 0.9 percent saline (i.p., control group) and LA (10, 20 or 30 mg/kg, i.p., LA10, LA20 and LA30 groups, respectively). After the treatments all groups were observed for 24 h. The NE and DA levels were increased only in 20 mg/kg dose of LA in rat hippocampus. Serotonin content and in their metabolite 5-HIAA levels was decreased in same dose of LA. On the other hand, in DOPAC and HVA levels did not show any significant change. The alterations in hippocampal monoamines can be suggested as a possible of brain mechanism of action from this antioxidant. The outcome of the study may have therapeutic implications in the treatment of neurodegenerative diseases.
O objetivo do presente estudo foi verificar a concentração das monoaminas (dopamina (DA), norepinefrina (NA), serotonina (5-HT)), e seus metabólitos (ácido 3,4-hidroxifenil (DOPAC), ácido homovanílico (HVA) e 5 ácido hydroxiindolacético (5-HIAA)) no hipocampo de ratos após administração do ácido lipóico (AL). Ratos Wistar foram tratados com solução salina 0,9 por cento (i.p., grupo controle) e AL (10, 20 ou 30 mg/kg, i.p., AL10, AL20 e AL30 grupos, respectivamente). Após os tratamentos todos os grupos foram observados durante 24 h. O conteúdo de DA no hipocampo de ratos foi aumentado apenas com AL na dose de 20 mg/kg dose. A concentração de serotonina e do seu metabólito 5-HIAA também foi diminuída com esta dose de AL. Por outro lado, os níveis de DOPAC e de HVA não mostrram nenhuma mudança significativa. As alterações na concentração das monoaminas hipocampais podem ser sugeridas como um possível mecanismo de ação cerebral deste antioxidante. O resultado do estudo pode ter implicações terapêuticas no tratamento de doenças neurodegenerativas.
Assuntos
Animais , Masculino , Ratos , Antioxidantes/farmacologia , Monoaminas Biogênicas/metabolismo , Hipocampo/efeitos dos fármacos , Ácido Tióctico/farmacologia , Hipocampo/metabolismo , Ratos WistarRESUMO
Temporal lobe epilepsy is the most common form of epilepsy in humans. Oxidative stress is a mechanism of cell death induced by seizures. Buspirone presents anxyolitic and antidepressant effects due to their ability to stimulate 5-HT(1A) receptor. We studied the buspirone effects on oxidative stress in rat hippocampus after seizures and status epilepticus (SE) induced by pilocarpine. In pilocarpine group there was a significant increase in lipid peroxidation and nitrite levels. However, no alteration was observed in superoxide dismutase and catalase activities. Buspirone pretreatment produces significantly reduction of the lipid peroxidation level (60%) and nitrite content (44%) as well as increased the superoxide dismutase (47%) and catalase (40%) activities in rat hippocampus after seizures, when compared with the pilocarpine group. The intraperitoneal injection of buspirone prior to pilocarpine suppressed the behavioral seizure occurrence. According to our results, the oxidative stress is present during seizures. Buspirone exerted anticonvulsant effects associated with the inhibition of the development of oxidative stress. These results suggest a therapeutic use potential of buspirone in epilepsy treatment.
Assuntos
Buspirona/farmacologia , Hipocampo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Convulsões/tratamento farmacológico , Convulsões/fisiopatologia , Agonistas do Receptor de Serotonina/farmacologia , Animais , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/farmacologia , Buspirona/administração & dosagem , Catalase/metabolismo , Hipocampo/fisiopatologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Nitritos/metabolismo , Estresse Oxidativo/fisiologia , Pilocarpina , Ratos , Ratos Wistar , Convulsões/induzido quimicamente , Agonistas do Receptor de Serotonina/administração & dosagem , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/tratamento farmacológico , Estado Epiléptico/fisiopatologia , Superóxido Dismutase/metabolismo , Fatores de TempoRESUMO
Recent researches have shown that antioxidant compounds may have certain neuroprotective effect against the neurotoxicity of seizures at cellular level. Ubiquinone (UQ), an antioxidant compound, exhibits a wide range of therapeutic effects that are attributed to its potent antioxidant capacity. The objective of the present study was to evaluate the neuroprotective effects of UQ in rats, against the observed oxidative stress during seizures induced by pilocarpine. Wistar rats were treated with either 0.9% saline (i.p., control group), UQ (5, 10 or 20 mg/kg, i.p., UQ5, UQ10 and UQ20 groups), pilocarpine (400 mg/kg, i.p., P400 group), or co-administration of pilocarpine with UQ group rats 30 min prior to UQ administration. After the treatments all groups were observed for 24 h. The antioxidant enzymatic activities as well as the hydroperoxide concentrations were measured using spectrophotometric methods and the results were analyzed. In pilocarpine group there was a significant increase in hydroperoxides concentration and glutathione peroxidase activity. However, no alteration was observed in superoxide dismutase and catalase activities. Antioxidant treatment significantly reduced the hydroperoxide content and increased the superoxide dismutase, catalase and glutathione peroxidase activities in rat hippocampus during seizures induced by pilocarpine. Our findings strongly support the hypothesis that oxidative stress in hippocampus occurs during seizures induced by pilocarpine, which indicates that brain damage induced by the oxidative process plays a crucial role in seizures pathogenic consequences. Our result also suggests that ubiquinone can exert significant neuroprotective effects that might be useful in the treatment of neurodegenerative diseases.
Assuntos
Antioxidantes/metabolismo , Hipocampo/efeitos dos fármacos , Peróxido de Hidrogênio/metabolismo , Fármacos Neuroprotetores/farmacologia , Convulsões/tratamento farmacológico , Ubiquinona/farmacologia , Animais , Catalase/metabolismo , Relação Dose-Resposta a Droga , Glutationa Peroxidase/metabolismo , Hipocampo/enzimologia , Hipocampo/metabolismo , Masculino , Fármacos Neuroprotetores/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Pilocarpina , Ratos , Ratos Wistar , Convulsões/induzido quimicamente , Convulsões/metabolismo , Superóxido Dismutase/metabolismo , Fatores de Tempo , Ubiquinona/administração & dosagemRESUMO
Ascorbic acid has many nonenzymatic actions and is a powerful water-soluble antioxidant. It protects low density lipoproteins from oxidation and reduces harmful oxidants in the central nervous system. Pilocarpine-induced seizures have been suggested to be mediated by increases in oxidative stress. Current studies have suggested that antioxidant compounds may afford some level of neuroprotection against the neurotoxicity of seizures. The objective of the present study was to evaluate the neuroprotective effects of ascorbic acid (AA) in rats, against the observed oxidative stress during seizures induced by pilocarpine. Wistar rats were treated with 0.9% saline (i.p., control group), ascorbic acid (500 mg/kg, i.p., AA group), pilocarpine (400 mg/kg, i.p., pilocarpine group), and the association of ascorbic acid (500 mg/kg, i.p.) plus pilocarpine (400 mg/kg, i.p.), 30 min before of administration of ascorbic acid (AA plus pilocarpine group). After the treatments all groups were observed for 6h. The enzyme activities as well as the lipid peroxidation and nitrite concentrations were measured using spectrophotometric methods and the results compared to values obtained from saline and pilocarpine-treated animals. Protective effects of ascorbic acid were also evaluated on the same parameters. In pilocarpine group there was a significant increase in lipid peroxidation and nitrite level. However, no alteration was observed in superoxide dismutase and catalase activities. Antioxidant treatment significantly reduced the lipid peroxidation level and nitrite content as well as increased the superoxide dismutase and catalase activities in hippocampus of adult rats after seizures induced by pilocarpine. Our findings strongly support the hypothesis that oxidative stress in hippocampus occurs during seizures induced by pilocarpine, proving that brain damage induced by the oxidative process plays a crucial role in seizures pathogenic consequences, and also imply that a strong protective effect could be achieved using ascorbic acid.