RESUMO
Our working hypothesis is that brain neurotrophins and brain Na(+),K(+)-ATPase may be strongly associated with the occurrence of depression in animals subjected to chronic unpredictable mild stress (CUMS). Still, we believe that chrysin, a natural and bioactive flavonoid found in honey and some plants, can provide satisfactory effects on antidepressant therapy. Thus, we aimed to evaluate the effect of CUMS on brain-derived neurotropic factor (BDNF) and nerve growth factor (NGF) levels as well as the Na(+),K(+)-ATPase activity in the hippocampus and prefrontal cortex of female mice. We also aimed to examine the effect of a 28-day oral treatment with chrysin (5 or 20mg/kg) in female mice subjected to CUMS, comparing to the effect of fluoxetine. Results showed that CUMS applied for 28days induced a decrease in BDNF and NGF levels as well as in the Na(+),K(+)-ATPase activity. CUMS also promoted a depressive status in the swimming forced test (FST), in the sucrose preference test, and in corticosterone levels. Chrysin (20mg/kg) and fluoxetine also occasioned the up-regulation of BDNF and NGF levels in non-stressed mice and in mice subjected to CUMS. CUMS decreased non-protein thiol (NPSH) levels and increased reactive oxygen species (ROS) levels. In response to these changes, the glutathione reductase (GR), glutathione peroxidase (GPx) and catalase (CAT) activities were increased in mice exposed to CUMS. Chrysin and fluoxetine treatments protected against all these alterations, suggesting the involvement of the antioxidant function in the antidepressant effect of chrysin and fluoxetine. In conclusion, CUMS decreased BDNF and NGF levels as well as the Na(+),K(+)-ATPase activity in mice. Chrysin presented antidepressant effect in mice on behavioral, neurotrophic and biochemistry parameters equivalent to fluoxetine. Furthermore, we suggest that the up-regulation of BDNF and NGF levels is a mechanism possibly involved in the antidepressant effect of chrysin in mice.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipocampo/metabolismo , Fator de Crescimento Neural/metabolismo , Córtex Pré-Frontal/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Estresse Psicológico/metabolismo , Animais , Antidepressivos/farmacologia , Antioxidantes/farmacologia , Catalase/metabolismo , Doença Crônica , Corticosterona/metabolismo , Transtorno Depressivo/tratamento farmacológico , Transtorno Depressivo/metabolismo , Modelos Animais de Doenças , Feminino , Flavonoides/farmacologia , Fluoxetina/farmacologia , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Hipocampo/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Córtex Pré-Frontal/efeitos dos fármacos , Estresse Psicológico/tratamento farmacológico , Incerteza , Regulação para Cima/efeitos dos fármacosRESUMO
Parkinson's disease (PD) is characterized by progressive dopamine (DA) depletion in the striatum. Exercise has been shown to be a promising non-pharmacological approach to reduce the risk of neurodegeneration diseases. This study was designed to investigate the potential neuroprotective effect of swimming training (ST) in a mouse model of PD induced by 6-hydroxydopamine (6-OHDA) in mice. The present study demonstrated that a 4-week ST was effective in attenuating the following impairments resulting from 6-OHDA exposure: (i) depressive-like behavior in the tail suspension test; (ii) increase in the number of falls in the rotarod test; (iii) impairment on long-term memory in the object recognition test; (iv) increase of the reactive species and interleukin 1-beta (IL-1ß) levels; (v) inhibition of the glutathione peroxidase (GPx) activity; (vi) rise of the glutathione reductase (GR) and glutathione S-transferase (GST) activities and vii) decrease of DA, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels. The mechanisms involved in this study are the modulation of GPx, GR and GST activities as well as IL-1ß level in a PD model induced by 6-OHDA, protecting against the decrease of DA, DOPAC and HVA levels in the striatum of mice. These findings reinforce that one of the effects induced by exercise on neurodegenerative disease, such as PD, is due to antioxidant and anti-inflammatory properties. We suggest that exercise attenuates cognitive and motor declines, depression, oxidative stress, and neuroinflammation induced by 6-OHDA supporting the hypothesis that exercise can be used as a non-pharmacological tool to reduce the symptoms of PD.
Assuntos
Terapia por Exercício/métodos , Hidroxidopaminas/toxicidade , Doença de Parkinson/etiologia , Doença de Parkinson/reabilitação , Natação/fisiologia , Animais , Catalase/metabolismo , Citrato (si)-Sintase/metabolismo , Corpo Estriado/enzimologia , Depressão/etiologia , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Elevação dos Membros Posteriores , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/enzimologia , Doença de Parkinson/fisiopatologia , Desempenho Psicomotor , Reconhecimento Psicológico , Teste de Desempenho do Rota-RodRESUMO
In this study, we investigated the effects of 2,2'-dithienyl diselenide (DTDS), an organoselenium compound, against seizures induced by kainic acid (KA) in rats. Rats were pretreated with DTDS (50 or 100 mg/kg) by oral route 1 h before KA injection (10 mg/kg, intraperitoneal). Our results showed that DTDS (100 mg/kg) was effective in increasing latency for the onset of the first clonic seizure episode induced by KA, as well as in decreasing the appearance of seizures and the Racine's score. DTDS also caused a decrease in the excitatory electroencephalographic (EEG) changes, resulting from KA exposure in hippocampus and cerebral cortex of rats. Besides, elevated reactive species (RS) and carbonyl protein levels and Na(+), K(+)-ATPase activity in hippocampus of rats treated with KA were ameliorated by DTDS (50 and 100 mg/kg). Lastly, as evidenced by Cresyl-Violet stain, DTDS (100 mg/kg) elicited a protective effect against KA-induced neurodegeneration in rat hippocampus 7 days after KA injection. In conclusion, the present study showed that DTDS attenuated KA-induced status epilepticus in rats and the subsequent hippocampal damage.
Assuntos
Hipocampo/fisiopatologia , Fármacos Neuroprotetores/uso terapêutico , Síndromes Neurotóxicas/patologia , Síndromes Neurotóxicas/prevenção & controle , Compostos Organosselênicos/uso terapêutico , Tiofenos/uso terapêutico , Timidina/análogos & derivados , Compostos de Tritil/uso terapêutico , Análise de Variância , Animais , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Interações Medicamentosas , Eletroencefalografia , Glutationa Peroxidase/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Ácido Caínico/toxicidade , Masculino , Fármacos Neuroprotetores/química , Síndromes Neurotóxicas/complicações , Síndromes Neurotóxicas/etiologia , Neurotoxinas/toxicidade , Compostos Organosselênicos/química , Estresse Oxidativo/efeitos dos fármacos , Carbonilação Proteica/efeitos dos fármacos , Ratos , Ratos Wistar , Tempo de Reação/efeitos dos fármacos , Convulsões/etiologia , Convulsões/prevenção & controle , ATPase Trocadora de Sódio-Potássio/metabolismo , Compostos de Sulfidrila/metabolismo , Tiofenos/química , Timidina/química , Timidina/uso terapêutico , Compostos de Tritil/químicaRESUMO
Organoselenium compounds display important antioxidant activity and many biological activities interesting from pharmacological point of view. The aim of this study was to evaluate the hepatoprotective effect of p-methoxyl-diphenyl diselenide, a disubstituted diaryl diselenide, on acute liver injury induced by D-galactosamine (D-GalN) and lipopolysaccharide (LPS) in mice. The animals received p-methoxyl-diphenyl diselenide (10, 50 and 100 mg/kg; per oral, p.o.) and 1 h after d-GalN (500 mg/kg) and LPS (50 microg/kg) were administered by intraperitoneal route (i.p.). Twenty-four hours after LPS/d-GalN exposure the animals were euthanized to the biochemical and histological analysis. Pretreatment with p-methoxyl-diphenyl diselenide (50 and 100 mg/kg; p.o.) protected against the increase in aspartate aminotransferase (AST) activity induced by LPS/d-GalN exposure in mice. p-Methoxyl-diphenyl diselenide at the doses of 50 and 100 mg/kg protected against the increase in alanine aminotransferase (ALT) activity induced by LPS/D-GalN exposure. In this study, no alteration in ascorbic acid levels was observed in livers of mice exposed to LPS/D-GalN. Glutathione-S-transferase (GST) activity was stimulated by LPS/D-GalN exposure and p-methoxyl-diphenyl diselenide, at all doses, protected against this alteration. p-Methoxyl-diphenyl diselenide was effective in ameliorating inhibition of catalase activity induced by LPS/d-GalN exposure. Histological data showed that sections of livers from LPS/D-GalN-treated mice presented massive hemorrhage, inflammatory cells and necrosis. p-Methoxyl-diphenyl diselenide significantly attenuated LPS/D-GalN-induced hepatic histopathological alterations. Based on the results, we suggest the hepatoprotective effect of p-methoxyl-diphenyl diselenide on acute liver injury induced by LPS/d-GalN exposure in mice.
Assuntos
Antioxidantes/uso terapêutico , Derivados de Benzeno/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Falência Hepática Aguda/prevenção & controle , Compostos Organosselênicos/uso terapêutico , Administração Oral , Alanina Transaminase/metabolismo , Animais , Antioxidantes/farmacologia , Ácido Ascórbico/metabolismo , Aspartato Aminotransferases/metabolismo , Derivados de Benzeno/farmacologia , Catalase/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Relação Dose-Resposta a Droga , Galactosamina , Glutationa Transferase/metabolismo , Injeções Intraperitoneais , Lipopolissacarídeos , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/patologia , Masculino , Camundongos , Compostos Organosselênicos/farmacologiaRESUMO
The aim of the present study was to evaluate pharmacological and toxicological properties of (Z)-2-(methylthio)-1-(butyltelluro)-1-phenylethene 1a, (Z)-1-(4-methylphenylsulfonyl)-2-(phenyltelluro)-2-phenylethene 1b, (Z)-2-(butyltelluro)-1-(benzylthio)-1-heptene 1c and (Z)-2-(phenylthio)-1-(butyltelluro)-1-phenylethene 1d. In vitro, vinylic telluride derivatives 1a, 1d and 1c were more effective in reducing lipid peroxidation than compound 1b. The maximal inhibitory effect of vinylic telluride derivatives on lipid peroxidation was in the following order: 1a = 1d > 1c > 1b. Compound 1b was more potent in inhibiting delta-ALA-D activity (delta-aminolevulinate dehydratase) than compounds 1c and 1d. Based on the in vitro properties presented by compounds 1a (an antioxidant) and 1b (a pro-oxidant), toxicological parameters were assessed in vivo and ex vivo in rats. Calculated LD50 of compounds 1a and 1b, administered by oral route, were 20.5 and 1.44 micromol kg(-1), respectively. Compound 1b induced behavioral alterations in the open field test. Renal and spleenic delta-ALA-D activities were inhibited in rats treated orally with compound 1a. Compound 1b stimulated delta-ALA-D activity in liver and spleen of rats. Rats treated with compound 1b had increased hepatic, renal and spleenic lipid peroxidation. Renal and hepatic markers were not altered when compounds 1a and 1b were administered to rats at doses of around LD50, while compound 1a at high doses changed aspartate aminotransferase activity and urea levels. Based on in vitro results, this study demonstrated that compounds 1a and 1d are promising antioxidant compounds. Ex vivo data reinforce compound 1a as a promising drug for more detailed pharmacological studies.