Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.154
Filtrar
1.
Toxicol Lett ; 338: 85-96, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33309997

RESUMO

Disruption of neurite outgrowth is a marker for neurotoxicity. Persistent organic pollutants (POPs) are potential developmental neurotoxicants. We investigated their effect on neurite outgrowth in PC12 rat pheochromocytoma cells, in absence or presence of nerve growth factor (NGF), an inducer of neuronal differentiation. Cells were exposed for 72 h to a defined mixture of POPs with chemical composition and concentrations based on blood levels in the Scandinavian population. We also evaluated perfluorooctane sulfonic acid (PFOS) alone, the most abundant compound in the POP mixture. Only higher concentrations of POP mixture reduced tetrazolium salt (MTT) conversion. High-content analysis showed a decrease in cell number, but no changes for nuclear and mitochondrial cellular health parameters. Robust glutathione levels were observed in NGF-differentiated cells. Live imaging, using the IncuCyte ZOOM platform indicated ongoing cell proliferation over time, but slower in presence of NGF. The pollutants did not inhibit neuritogenesis, but rather increased NGF-induced neurite length. PFOS induced neurite outgrowth to about 50 % of the level seen with the POP mixture. Neither the POP mixture nor PFOS affected neurite length in the absence of NGF. Our observations indicate that realistic complex mixtures of environmental pollutants can affect neuronal connectivity via NGF-induced neurite outgrowth.


Assuntos
Ácidos Alcanossulfônicos/toxicidade , Poluentes Ambientais/toxicidade , Fluorcarbonetos/toxicidade , Fator de Crescimento Neural/farmacologia , Neuritos/efeitos dos fármacos , Crescimento Neuronal/efeitos dos fármacos , Síndromes Neurotóxicas/etiologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Glutamato-Cisteína Ligase/genética , Glutamato-Cisteína Ligase/metabolismo , Glutationa/metabolismo , Neuritos/metabolismo , Neuritos/patologia , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Células PC12 , Ratos , Fatores de Tempo
2.
Life Sci ; 266: 118876, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33310035

RESUMO

Prenatal exposure to arsenic is demonstrated to elevate the risk of brain damage and neurological disorders in the fetus, mainly due to its ability for crossing through the placental barriers. Increase in oxidative stress, inflammation, and DNA damage is main mechanisms of arsenic-induced neurotoxicity. Therefore, this study aimed to evaluate the neuroprotective effects of melatonin, as a potent anti-oxidant and anti-inflammatory agent against arsenic toxicity in the brains of male offspring rats. Pregnant mother rats were randomly assigned into four groups including group I, as control, group II received 10 mg/kg melatonin, group III received arsenic at 50 mg/kg, and group IV received melatonin and arsenic. After a two-month period, oxidative stress, DNA damage, inflammation and apoptosis were assessed in the male offspring rats. Exposure to arsenic significantly increased the pro-inflammatory and oxidative factors resulting in DNA damage and apoptosis in the brain tissues of offspring rats in comparison to controls (p < 0.05). Exogenous administration of melatonin showed a significant increase in the tissue levels of acetylcholine esterase, decrease in the lactate dehydrogenase and myeloperoxidase, when compared to arsenic group (p < 0.05). Melatonin also overcame the arsenic-induced oxidative stress and suppressed inflammation, DNA damage and apoptosis. Our results suggested that melatonin may be a promising neuro-protective agent and momentous therapy for the treatment of arsenic-toxicity in clinical conditions.


Assuntos
Arsênico/toxicidade , Inflamação/tratamento farmacológico , Melatonina/farmacologia , Fármacos Neuroprotetores/farmacologia , Síndromes Neurotóxicas/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Apoptose , Feminino , Inflamação/induzido quimicamente , Inflamação/patologia , Masculino , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/patologia , Gravidez , Ratos , Ratos Wistar , Transdução de Sinais
3.
Int J Nanomedicine ; 15: 5299-5315, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32884256

RESUMO

Purpose: Zinc oxide nanoparticles (ZnONPs) are one of the most important nanomaterials that are widely used in the food, cosmetic and medical industries. Humans are often exposed to ZnONPs via inhalation, and they may reach the brain where neurotoxic effects could occur via systemic distribution. However, the mechanisms underlying how ZnONPs produce neurotoxic effects in the brain remain unclear. In this study, we aimed to investigate the novel mechanism involved in ZnONPs-induced neurotoxicity. Methods and Results: We demonstrated for the first time that pulmonary exposure to ZnONPs by intratracheal instillation could trigger ferroptosis, a new form of cell death, in the neuronal cells of mouse cerebral cortex. A similar phenomenon was also observed in cultured neuron-like PC-12 cell line. By using a specific inhibitor of ferroptosis ferrostatin-1 (Fer-1), our results showed that inhibition of ferroptosis by Fer-1 could significantly alleviate the ZnONPs-induced neuronal cell death both in vivo and in vitro. Mechanistic investigation revealed that ZnONPs selectively activated the JNK pathway and thus resulted in the ferroptotic phenotypes, JNK inhibitor SP600125 could reverse lipid peroxidation upregulation and ferroptotic cell death induced by ZnONPs in PC-12 cells. Conclusion: Taken together, this study not only demonstrates that pulmonary exposure of ZnONPs can induce JNK-involved ferroptotic cell death in mouse cortex and PC-12 cells, but also provides a clue that inhibition of ferroptosis by specific agents or drugs may serve as a feasible approach for reducing the untreatable neurotoxicity induced by ZnONPs.


Assuntos
Ferroptose/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Neurônios/efeitos dos fármacos , Síndromes Neurotóxicas/patologia , Óxido de Zinco/toxicidade , Administração por Inalação , Animais , Antracenos/farmacologia , Morte Celular/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/patologia , Cicloexilaminas/farmacologia , Ferroptose/fisiologia , Peroxidação de Lipídeos/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Nanopartículas Metálicas/administração & dosagem , Camundongos Endogâmicos C57BL , Neurônios/patologia , Síndromes Neurotóxicas/etiologia , Células PC12 , Fenilenodiaminas/farmacologia , Ratos , Óxido de Zinco/administração & dosagem
4.
Pesqui. vet. bras ; 40(6): 443-450, June 2020. ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1135645

RESUMO

Poisonous plants are a significant cause of death among adult cattle in Brazil. Plants that affect the central nervous system are widely spread throughout the Brazilian territory and comprise over 30 toxic species, including the genus Ipomoea, commonly associated with a lysosomal storage disease and a tremorgenic syndrome in livestock. We describe natural and experimental Ipomoea pes caprae poisoning in cattle from a herd in the Northside of Rio de Janeiro, Brazil. Affected cattle presented episodes of severe ataxia, abnormal posture followed by falling, muscular tremor, contraction, and spasticity, more prominent in the limbs, intensified by movement and forthcoming, and recumbence. Grossly, a substantial amount of leaves and petioles were found in the rumen. Histopathological examination showed degenerative neuronal changes, mostly in cerebellar Purkinje cells, which were confirmed with Bielschowsky silver. The characteristic clinical changes and mild histological lesion strongly suggested a tremorgenic syndrome. Lectin- immunohistochemistry evaluation reinforced this hypothesis; all lectins tested failed to react with affect neurons and Purkinje cells, which ruled out an underlying lysosomal storage disease. One calf given I. pes caprae leaves experimentally developed clinical signs similar to natural cases. On the 28th day of the experiment, the plant administration was suspended, and the calf recovered within four days. I. pes caprae's spontaneous tremorgenic syndrome in cattle is conditioned to exclusive feeding for several months. We were able to experimentally reproduce toxic clinical signs 12 days following the ingestion.(AU)


A intoxicação por plantas tóxicas está entre as três causas de morte mais importantes em bovinos adultos no Brasil. O grupo das plantas que causam alterações neurológicas, muito bem representada no país, encerra mais de trinta espécies tóxicas, entre as quais do gênero Ipomoea, amplamente distribuídas no território brasileiro. As plantas tóxicas desse gênero podem causar doenças do armazenamento ou síndrome tremorgênica. Descrevem-se a intoxicação natural e reprodução experimental por Ipomoea pes caprae em bovinos, verificada no norte do Estado do Rio de Janeiro. Foram observados episódios de intensa ataxia locomotora, postura anormal seguida de queda, incapacidade de levantar-se, tremores, contrações, espasticidades musculares nos membros, intensificados após estimulação ou a simples aproximação e decúbito. Nos bovinos afetados há mais de 6 meses, os sinais clínicos tornavam-se permanentes. À necropsia havia apenas significativa quantidade de folhas e pecíolos da planta no rúmen. O estudo histopatológico evidenciou lesões neuronais degenerativas principalmente nos neurônios de Purkinje. A impregnação argêntica pela técnica de Bielschowsky ratificou esses achados microscópicos. As lesões histológicas sutis associadas ao quadro clínico indicam que trata-se de intoxicação tremorgênica. O fato de não haver nenhum armazenamento intracitoplasmático, confirmado pelo resultado do estudo lectino-histoquímico (não houve afinidade das lectinas Con-A, WGA e sWGA e de outras lectinas empregadas aos neurônios de Purkinje e outros neurônios afetados), é suficiente para descartar a possibilidade de tratar-se de doença do armazenamento. No bezerro intoxicado experimentalmente verificaram-se sinais clínicos semelhantes, entretanto, com a interrupção do fornecimento da planta no 28º dia, os sinais clínicos desapareceram após quatro dias. I. pes caprae causa síndrome tremorgênica espontânea em bovinos, quando ingerida como alimentação exclusiva durante períodos prolongados (muitos meses). Experimentalmente, os primeiros sinais clínicos da intoxicação foram reproduzidos após 12 dias de ingestão da planta.(AU)


Assuntos
Animais , Bovinos , Intoxicação por Plantas/veterinária , Intoxicação por Plantas/epidemiologia , Doenças dos Bovinos , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/patologia , Ipomoea/envenenamento , Tremor/etiologia , Tremor/veterinária , Síndromes Neurotóxicas/veterinária
5.
Sci Rep ; 10(1): 7283, 2020 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-32350290

RESUMO

Earlier studies showed that endogenous estrogens have neuroprotective effect against oxidative damage. The present study seeks to investigate the protective effect of various endogenous estrogen metabolites against oxidative neurotoxicity in vitro and in vivo. Using immortalized mouse hippocampal neuronal cells as an in vitro model, 4-hydroxyestrone, an estrone metabolite with little estrogenic activity, is found to have the strongest neuroprotective effect against oxidative neurotoxicity among 25 endogenous estrogen metabolites tested, and its protective effect is stronger than 17ß-estradiol. Similarly, 4-Hydroxyestrone also exerts a stronger protective effect than 17ß-estradiol against kanic acid-induced hippocampal oxidative damage in rats. Neuroprotection by 4-hydroxyestrone involves increased cytoplasmic translocation of p53 resulting from SIRT1-mediated deacetylation of p53. Analysis of brain microsomal enzymes shows that estrogen 4-hydroxylation is the main metabolic pathway in the central nervous system. Together, these results show that 4-hydroxyestrone is an endogenous neuroestrogen that can strongly protect against oxidative neuronal damage.


Assuntos
Hipocampo/metabolismo , Hidroxiestronas/farmacologia , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Linhagem Celular Transformada , Estradiol/farmacologia , Hipocampo/patologia , Masculino , Camundongos , Neurônios/patologia , Síndromes Neurotóxicas/tratamento farmacológico , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Ratos , Ratos Sprague-Dawley
6.
Chemosphere ; 256: 127069, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32447111

RESUMO

Pesticides are proposed as one reason for the worldwide decline in the reptile. Effects of pesticides on food intake and organ toxicity could affect wildlife populations dynamics. To explore the hepatotoxicity of alpha-cypermethrin (ACP) in reptiles, we designed a tri-trophic food chain with three concentrations (0, 2, and 20 mg/kgwet weight). Although the enzymes changes were similar between male and female lizards, the significant variations in anti-oxidative enzymes' activities, lactic dehydrogenase activities and acetylcholine esterase activities in liver and kidney suggesting that oxidative stress, decreased metabolic ability and neurotoxicity on lizards. The results of hepatic metabolomics showed that ACP could affect amino acid, energy and lipid metabolism on lizards. Comparing with female lizards, there were more significant changes of metabolites in male lizards. The histopathology analysis in the liver (such as hepatic lobule congestion and hepatocyte vacuolation) and kidney (such as renal tubule necrosis and glomerulus necrosis), dose- and gender dependent changes of lesions suggested the functions of organ were damaged. In summary, the reduction of detoxification and elimination capacities of the liver and kidney showed dose/gender-dependent in lizards.


Assuntos
Praguicidas/toxicidade , Piretrinas/toxicidade , Animais , Doença Hepática Induzida por Substâncias e Drogas/patologia , Relação Dose-Resposta a Droga , Feminino , Cadeia Alimentar , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Lagartos/metabolismo , Masculino , Síndromes Neurotóxicas/patologia , Estresse Oxidativo/fisiologia , Praguicidas/metabolismo
7.
Toxicology ; 438: 152442, 2020 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-32278051

RESUMO

Bisphenol A (BPA) is a well-known endocrine disruptor used to manufacture polycarbonate plastics and epoxy resins. BPA exposure especially occupational perinatal exposure to has been linked to numerous adverse effects for the offspring. Available data have shown that perinatal exposure to BPA contributes to neurodegenerative pathological changes; however, the potential mechanisms remain unclear. This study attempted to investigate the long-term consequences of perinatal exposure to BPA on the offspring mouse brain. The pregnant mice were given either a vehicle control or BPA (2, 10, 100 µg/kg/d) from day 6 of gestation until weaning (P6-PND21, foetal and neonatal exposure). At 3, 6 and 9 months of age, the neurotoxic effects in the offspring in each group were investigated. We found that the spine density but not the dendritic branches in the hippocampus were noticeably reduced at 6 and 9 months of age. Meanwhile, p-Tau, the characteristic protein for tauopathy, was dramatically increased in both the hippocampus and cortex at 3-9 months of age. Mechanically, the balance of kinase and protein phosphatase, which plays critical roles in p-Tau regulation, was disturbed. It indicated that GSK3ß and CDK5, two critical kinases, were activated in most of the BPA perinatal exposure group, while protein phosphatase 2A (PP2A), one of the important phosphatases, regulated p-Tau expression through its demethylation, methylation and phosphorylation. Taken together, the present study may be translatable to the human occupational BPA exposure due to a similar exposure level. BPA perinatal exposure causes long-term adverse effects on the mouse brain and may be a risk factor for tauopathies, and the CDK5/GSK3ß/PP2A axis might be a promising therapeutic target for BPA-induced neurodegenerative pathological changes.


Assuntos
Compostos Benzidrílicos/toxicidade , Córtex Cerebral/efeitos dos fármacos , Quinase 5 Dependente de Ciclina/metabolismo , Disruptores Endócrinos/toxicidade , Glicogênio Sintase Quinase 3 beta/metabolismo , Hipocampo/efeitos dos fármacos , Síndromes Neurotóxicas/etiologia , Fenóis/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Proteína Fosfatase 2/metabolismo , Proteínas tau/metabolismo , Animais , Córtex Cerebral/enzimologia , Córtex Cerebral/patologia , Espinhas Dendríticas/efeitos dos fármacos , Espinhas Dendríticas/enzimologia , Espinhas Dendríticas/patologia , Feminino , Idade Gestacional , Hipocampo/enzimologia , Hipocampo/patologia , Masculino , Exposição Materna , Camundongos Endogâmicos C57BL , Síndromes Neurotóxicas/enzimologia , Síndromes Neurotóxicas/patologia , Fosforilação , Gravidez
8.
Toxicology ; 438: 152461, 2020 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-32278788

RESUMO

The α-Synuclein (α-syn) and tau have synergistic effects on neurodegenerative diseases induced by environmental factors or genetic mutation. Thus, we investigated the role of α-syn and tau in neurodegeneration induced by chronic methamphetamine (METH) exposure (1.0∼20.0 mg/kg/d body weight, for 14 consecutive days). Here, we present a mice model with evidences of α-syn and tau participating in toxicology in chronic METH. METH increased α-syn level in the stratum oriens, pyramidal layer, stratum radiatum and stratum moleculare of hippocampal CA1, CA2 and CA3, polymorph layer of hippocampal dentate gyrus (DG), and substantia nigra (SN). The subcellular locations of the upregulated α-syn were mainly found in mitochondria and axons. The METH upregulated α-syn may directly induce mitochondrial damage, myelin sheath destruction, and synaptic failure. Also, the excess α-syn might indirectly promote tau phosphorylation through tau kinase GSK3ß and CDK5, leading to microtubule depolymerization and eventually fusion deficit of autophagosome and lysosome. In the in vitro experiment, the autophagic vacuoles failed to fuse with the lysosome. The neuropathology induced by both the direct and indirect effects of α-syn could be alleviated by α-syn knockout. Taking together, these results indicate that the α-syn mediates the neurodegenerative process induced by chronic METH and that reducing α-syn might be a potential approach to protect the toxic effects of METH and also be, to a broader view, of therapeutic value in neurodegenerative diseases.


Assuntos
Hipocampo/metabolismo , Degeneração Neural , Neurônios/metabolismo , Síndromes Neurotóxicas/prevenção & controle , Substância Negra/metabolismo , alfa-Sinucleína/deficiência , Animais , Autofagia , Axônios/metabolismo , Axônios/ultraestrutura , Células Cultivadas , Quinase 5 Dependente de Ciclina/metabolismo , Modelos Animais de Doenças , Glicogênio Sintase Quinase 3 beta/metabolismo , Hipocampo/ultraestrutura , Lisossomos/metabolismo , Lisossomos/ultraestrutura , Masculino , Metanfetamina , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Neurônios/ultraestrutura , Síndromes Neurotóxicas/genética , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Fosforilação , Substância Negra/ultraestrutura , Fatores de Tempo , alfa-Sinucleína/genética , Proteínas tau/metabolismo
9.
Ecotoxicol Environ Saf ; 195: 110479, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32199213

RESUMO

Cypermethrin (CYP), a class II synthetic pyrethroid, is used to control household insects. CYP can cross the blood-brain barrier to exert neurotoxicity through changes in sodium ion channels. Selenium is an essential component of glutathione peroxidise enzyme; in addition, it shows a potential anti-inflammatory property. The present study aimed to investigate the neuroprotective role of Nano-Se on CYP-induced neurotoxicity. Twenty-four adult male Wister rats were randomly divided into three groups: a) control, b) CYP (1mg/kg) administered orally for 21 days, c) CYP (1mg/kg) administered orally for 21 days and Nano-Se (2.5 mg/kg) given once a day three times a week for three weeks). Locomotor activity was assessed using open field test then rats were sacrificed under anaesthesia, and their brains were dissected out and processed for biochemical and histopathological studies. Histological examination of CYP-treated rats demonstrated some degenerative changes; besides, CYP affected rat locomotor activity. CYP-treated rats showed increased levels of malondialdehyde (MDA), TNF-α and IL-1ß in addition to the reduction of glutathione (GSH) levels and gamma-Aminobutyric acid (GABA). Nano-Se restored normal behavioural function and significantly attenuated CYP-evoked degenerative changes. Nano-Se increased levels of GABA and glutathione; on the other hand, it significantly prevented the rise in the levels of MDA, TNF-α and IL-1ß. Therefore, Nano-Se demonstrated both anti-oxidant and anti-inflammatory potential. Nano-Se may be suggested to be a prospective candidate to ameliorate CYP-induced neurotoxicity.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Inseticidas/toxicidade , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Piretrinas/toxicidade , Selênio/farmacologia , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Citocinas/metabolismo , Glutationa/metabolismo , Masculino , Malondialdeído/metabolismo , Nanopartículas/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Síndromes Neurotóxicas/tratamento farmacológico , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Ratos , Ratos Wistar , Selênio/uso terapêutico , Ácido gama-Aminobutírico/metabolismo
10.
Oxid Med Cell Longev ; 2020: 2963020, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32215171

RESUMO

Organophosphorus insecticides including chlorpyrifos (CPF) are mainly used for agriculture, household, and military purposes; their application is associated with various adverse reactions in animals and humans. This study was conducted to evaluate the potential neuroprotective effect of red beetroot methanolic extract (RBR) against CPF-induced cortical damage. Twenty-eight adult male Wistar albino rats were divided into 4 groups (n = 7 in each group): the control group was administered physiological saline (0.9% NaCl), the CPF group was administered CPF (10 mg/kg), the RBR group was administered RBR (300 mg/kg), and the RBR+CPF group was treated with RBR (300 mg/kg) 1 hr before CPF (10 mg/kg) supplementation. All groups were treated for 28 days. Rats exposed to CPF exhibited a significant decrease in cortical acetylcholinesterase activity and brain-derived neurotrophic factor and a decrease in glial fibrillary acidic protein. CPF intoxication increased lipid peroxidation, inducible nitric oxide synthase expression, and nitric oxide production. This was accompanied by a decrease in glutathione content and in the activities of glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase in the cortical tissue. Additionally, CPF enhanced inflammatory response, indicated by increased levels and expression of interleukin-1ß and tumor necrosis factor-α. CPF triggered neuronal apoptosis by upregulating Bax and caspase-3 and downregulating Bcl-2. However, RBR reversed the induced neuronal alterations following CPF intoxication. Our findings suggest that RBR can minimize and prevent CPF neurotoxicity through its antioxidant, anti-inflammatory, and antiapoptotic activities.


Assuntos
Antioxidantes/administração & dosagem , Beta vulgaris/química , Clorpirifos/toxicidade , Fármacos Neuroprotetores/administração & dosagem , Síndromes Neurotóxicas/prevenção & controle , Extratos Vegetais/administração & dosagem , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Inflamação , Inseticidas/toxicidade , Masculino , Fármacos Neuroprotetores/farmacologia , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Ratos , Ratos Wistar
11.
Curr Pharm Biotechnol ; 21(12): 1259-1268, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32196446

RESUMO

BACKGROUND: Ginkgo biloba extract (GbE) is known to contain several bioactive compounds and exhibits free radical scavenging activity. Parkinson's Disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons and is associated with oxidative stress, neuroinflammation and apoptosis. OBJECTIVE: The current study aimed to investigate the neuroprotective effect of GbE in a rat model of PD induced by rotenone (ROT; a neurotoxin). METHODS: Twenty-four male albino rats were randomly divided into four groups of six rats each: normal control, GbE treated, toxin control (ROT treated) and GbE+ROT group. RESULTS: Oral administration of ROT (2.5 mg/kg b.w.) for 50 days caused an increased generation of lipid peroxidation products and significant depletion of reduced glutathione, total thiol content and activities of enzymatic antioxidants, i.e., superoxide dismutase and glutathione peroxidase in the brains of treated rats. Furthermore, ROT caused an elevation in acetylcholinesterase, interleukin-1ß, interleukin- 6 and tumor necrosis factor-α and a significant reduction in dopamine in the stratum and substantia nigra. Immunohistochemical results illustrated that ROT treatment reduced the expression of tyrosine hydroxylase (TH). GbE treatment (150 mg/kg b.w./day) significantly reduced the elevated oxidative stress markers and proinflammatory cytokines and restored the reduced antioxidant enzyme activities, DA level and TH expression. These results were confirmed by histological observations that clearly indicated a neuroprotective effect of GbE against ROT-induced PD. CONCLUSION: GbE mitigated ROT-induced PD via the inhibition of free-radical production, scavenging of ROS, and antioxidant enhancement.


Assuntos
Encéfalo/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Síndromes Neurotóxicas/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Administração Oral , Animais , Antioxidantes/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Citocinas/metabolismo , Suplementos Nutricionais , Modelos Animais de Doenças , Dopamina/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Fármacos Neuroprotetores/administração & dosagem , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Extratos Vegetais/administração & dosagem , Distribuição Aleatória , Ratos , Rotenona/toxicidade , Superóxido Dismutase/metabolismo
12.
Br J Anaesth ; 124(5): 603-613, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32151384

RESUMO

BACKGROUND: The most currently used general anaesthetics are potent potentiators of γ-aminobutyric acid A (GABAA) receptors and are invariably neurotoxic during the early stages of brain development in preclinical animal models. As causality between GABAA potentiation and anaesthetic-induced developmental neurotoxicity has not been established, the question remains whether GABAergic activity is crucial for promoting/enhancing neurotoxicity. Using the neurosteroid analogue, (3α,5α)-3-hydroxy-13,24-cyclo-18,21-dinorchol-22-en-24-ol (CDNC24), which potentiates recombinant GABAA receptors, we examined whether this potentiation is the driving force in inducing neurotoxicity during development. METHODS: The neurotoxic potential of CDNC24 was examined vis-à-vis propofol (2,6-diisopropylphenol) and alphaxalone (5α-pregnan-3α-ol-11,20-dione) at the peak of rat synaptogenesis. In addition to the morphological neurotoxicity studies of the subiculum and medial prefrontal cortex (mPFC), we assessed the extra-, pre-, and postsynaptic effects of these agents on GABAergic neurotransmission in acute subicular slices from rat pups. RESULTS: CDNC24, like alphaxalone and propofol, caused dose-dependent hypnosis in vivo, with a higher therapeutic index. CDNC24 and alphaxalone, unlike propofol, did not cause developmental neuroapoptosis in the subiculum and mPFC. Propofol potentiated post- and extrasynaptic GABAA currents as evidenced by increased spontaneous inhibitory postsynaptic current (sIPSC) decay time and prominent tonic currents, respectively. CDNC24 and alphaxalone had a similar postsynaptic effect, but also displayed a strong presynaptic effect as evidenced by decreased frequency of sIPSCs and induced moderate tonic currents. CONCLUSIONS: The lack of neurotoxicity of CDNC24 and alphaxalone may be at least partly related to suppression of presynaptic GABA release in the developing brain.


Assuntos
Encéfalo/efeitos dos fármacos , Hipnóticos e Sedativos/toxicidade , Pregnanodionas/toxicidade , Esteroides/toxicidade , Animais , Apoptose/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Relação Dose-Resposta a Droga , Agonistas de Receptores de GABA-A/administração & dosagem , Agonistas de Receptores de GABA-A/farmacologia , Agonistas de Receptores de GABA-A/toxicidade , Hipocampo/efeitos dos fármacos , Hipocampo/crescimento & desenvolvimento , Hipocampo/metabolismo , Hipocampo/patologia , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacologia , Potenciais Pós-Sinápticos Inibidores/efeitos dos fármacos , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/patologia , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/crescimento & desenvolvimento , Córtex Pré-Frontal/patologia , Pregnanodionas/administração & dosagem , Pregnanodionas/farmacologia , Propofol/administração & dosagem , Propofol/farmacologia , Propofol/toxicidade , Ratos Sprague-Dawley , Receptores de GABA-A/metabolismo , Esteroides/administração & dosagem , Esteroides/farmacologia , Sinapses/efeitos dos fármacos , Sinapses/fisiologia
13.
Toxicology ; 432: 152392, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32014472

RESUMO

Acrylamide (AA) constitutes an important industrial chemical agent and well-known neurotoxin. However, the mechanism underlying AA-mediated neurotoxicity is extremely complicated and controversial. In this study, we found that activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome and its subsequent downstream inflammatory responses plays an important role in AA-induced neurotoxicity mechanisms. In vitro experiments revealed that AA (2.5 mM) induced BV2 microglial cytotoxicity and triggered NLRP3 inflammasome activation along with downstream proinflammatory cytokine interleukin-1ß and interleukin-18 expression. Treatment with inhibitor or NLRP3 siRNA efficiently protected BV2 microglial cells against AA-induced cytotoxicity and reversed NLRP3 inflammasome activation and its mediated inflammatory reaction. Similarly, AA exposure (50 mg/kg) for 10 consecutive days caused significant activation of NLRP3 inflammasomes and neuroinflammation in C57BL/6 mice, whereas inhibiting these effects through specific NLRP3 inflammasome blocker MCC950 (5 mg/kg) intervention or NLRP3 knock-out significantly ameliorated AA-induced ataxia, cerebellar Purkinje cells degeneration, and apoptosis. Furthermore, we demonstrated that antagonism of NLRP3 could also up-regulate the Nrf2 signalling pathway and related antioxidant genes. In conclusion, our findings indicate that activation of the NLRP3 inflammasome pathway is involved in AA-induced neurotoxicity, whereas MCC950 treatment or NLRP3 knock-out could effectively protect against AA-induced neurotoxic injury through the inhibition of neuroinflammation and activation of the Nrf2 antioxidant pathway. Therefore, the NLRP3 inflammasome might serve as a promising therapeutic target, with drugs designed to specifically inhibit this pathway potentially providing new avenues for preventing or ameliorating AA poisoning.


Assuntos
Acrilamidas/toxicidade , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Síndromes Neurotóxicas/prevenção & controle , Animais , Comportamento Animal/efeitos dos fármacos , Linhagem Celular , Citocinas/metabolismo , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Inflamação/induzido quimicamente , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microglia/efeitos dos fármacos , Microglia/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Síndromes Neurotóxicas/patologia , Síndromes Neurotóxicas/psicologia , RNA Interferente Pequeno/farmacologia , Transdução de Sinais/efeitos dos fármacos , Sulfonas/farmacologia
14.
Toxicology ; 432: 152393, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32027964

RESUMO

Humans from fetal to adult stages are chronically and passively exposed to bisphenol A (BPA, an endocrine disruptor) due to its ubiquitous existence in daily life. To investigate the long-term neurotoxicity of maternal exposure to BPA for offspring, mice were used as the animal model. In this study, pregnant mice (F0) were orally dosed with BPA (i.e. mice from low-, medium- and high-exposed groups were treated with 0.5, 50, 5000 µg/kg·bw of BPA per day) until weaning. Then, the first generation (F1) mice were used to generate the F2 ones. The offspring of mice not exposed to BPA served as the control groups. The Y-maze test, comet assay, hematoxylin-eosin (HE) staining method, Golgi-Cox assay and liquid chromatography-tandem mass spectrometry (LC/MS/MS) were conducted to study any alterations to learning and memory abilities, the morphological variations in hippocampal neurons and transmitter levels of F1 and F2 mice induced by BPA exposure. Results showed that even a low-dose of maternal BPA exposure could sex-dependently and significantly impair the learning and memory ability of F1 male mice, but not of generation F2. Furthermore, decreased neuron quantities and spine densities in hippocampi were observed in both F1 and F2 generations after maternal BPA exposure. However, DNA damage of brain cells were only limited to F1 offspring, in which DNA damage was only observed in the low-exposed male mice and medium-exposed female mice. Additionally, maternal BPA exposure leads to variations in hippocampal neurotransmitter levels, indicated by the decreased ratio of Glu/GABA in F1 offspring. In conclusion, maternal exposure to an environmental dose of BPA resulted in lasting adverse effects on neurological development for offspring mice.


Assuntos
Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Hipocampo/efeitos dos fármacos , Exposição Materna/efeitos adversos , Neurônios/efeitos dos fármacos , Síndromes Neurotóxicas/patologia , Síndromes Neurotóxicas/psicologia , Fenóis/toxicidade , Animais , Ensaio Cometa , Dano ao DNA , Espinhas Dendríticas/efeitos dos fármacos , Espinhas Dendríticas/patologia , Feminino , Hipocampo/metabolismo , Hipocampo/patologia , Aprendizagem/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Camundongos , Neurônios/metabolismo , Neurotransmissores/metabolismo , Gravidez , Caracteres Sexuais
15.
Environ Toxicol ; 35(6): 683-696, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32061141

RESUMO

Methylmercury (MeHg) is a potent neurotoxin,which leads to a wide range of intracellular effects. The molecular mechanismsassociated to MeHg-induced neurotoxicity have not been fully understood.Oxidative stress, as well as synaptic glutamate (Glu) dyshomeostasis have beenidentified as two critical mechanisms during MeHg-mediated cytotoxicity. Here,we developed a rat model of MeHg poisoning to evaluate its neurotoxic effectsby focusing on cellular oxidative stress and synaptic Glu disruption. Inaddition, we investigated the neuroprotective role of alpha-lipoic acid (α-LA), a natural antioxidant, todeeply explore the underlying interaction between them. Fifty-six rats wererandomly divided into four groups: saline control, MeHg treatment (4 or 12µmol/kg MeHg), and α-LApre-treatment (35 µmol/kg α-LA+12µmol/kg MeHg). Rats exposed to 12 µmol/kg MeHg induced neuronal oxidativestress, with ROS accumulation and cellular antioxidant system impairment. Nrf2 andxCT pathways were activated with MeHg treatment. The enzymatic or non-enzymaticof cellular GSH synthesis were also disrupted by MeHg. On the other hand, the abnormalactivities of GS and PAG disturbed the "Glu-Gln cycle", leading to NMDARsover-activation, Ca2+ overload, and the calpain activation, which acceleratedNMDARs degradation. Meanwhile, the high expressions of phospho-p44/42 MAPK,phospho-p38 MAPK, phospho-CREB, and the high levels of caspase 3 and Bax/Bcl-2 finallyindicated the neuronal apoptosis after MeHg exposure. Pre-treatment with α-LA significantly preventedMeHg-induced neurotoxicity. In conclusion, the oxidative stress and synapticGlu dyshomeostasis contributed to MeHg-induced neuronal apoptosis. Alpha-LAattenuated these toxic effects through mechanisms of anti-oxidation andindirect Glu dyshomeostasis prevention.


Assuntos
Apoptose/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Ácido Glutâmico/metabolismo , Compostos de Metilmercúrio/toxicidade , Neurônios/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/metabolismo , Animais , Antioxidantes/metabolismo , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Masculino , Neurônios/metabolismo , Neurônios/patologia , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia , Oxirredução , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Ácido Tióctico/farmacologia
16.
Toxicol Lett ; 322: 66-76, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31945382

RESUMO

Silent Information Regulator 1 (SIRT1), an NAD+-dependent deacetylase, contributes to the neuroprotective effect. However, intracellular signaling pathways that affect SIRT1 function remain unknown. It is well known that N-methyl-D-aspartate (NMDA) receptor activation induces calcium influx which then activates PKC, and SIRT1 is a mRNA target for HuR protein. We hypothesize that Ca2+-PKC-HuR-SIRT1 pathway modulates SIRT1 function. The present study is to investigate the potential pathway of SIRT1 in the SH-SY5Y cell line as an in vitro model of NMDA-induced neurotoxicity. The results showed that: (1) SIRT1 levels were downregulated in NMDA model; (2) NMDA induced an increase in serine phosphorylation of HuR, while inhibition of serine phosphorylation of HuR increased SIRT1 levels, promoting cell survival; (3) PKC inhibitor (Gö 6976) reversed NMDA insults and also suppressed serine phosphorylation of HuR; (4) 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM), an intracellular calcium chelator, fully reversed NMDA insults and also inhibited PKC activity evoked by NMDA. These results indicate that intracellular elevated Ca2+ activates PKC, which phosphorylates HuR and then promotes SIRT1 mRNA decay and subsequent neuronal death in NMDA model. Therefore, the study suggests that inhibition of Ca2+-PKC-HuR-SIRT1 pathway could be an effective strategy for preventing certain neurological diseases related to NMDA excitotoxicity.


Assuntos
Agonistas de Aminoácidos Excitatórios/toxicidade , N-Metilaspartato/toxicidade , Neurônios/efeitos dos fármacos , Síndromes Neurotóxicas/etiologia , Sirtuína 1/metabolismo , Cálcio/metabolismo , Sinalização do Cálcio , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação para Baixo , Proteína Semelhante a ELAV 1/metabolismo , Humanos , Neurônios/enzimologia , Neurônios/patologia , Síndromes Neurotóxicas/enzimologia , Síndromes Neurotóxicas/patologia , Fosforilação , Proteína Quinase C/metabolismo , Estabilidade de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Serina , Sirtuína 1/genética
17.
Toxicology ; 432: 152364, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-31927068

RESUMO

Environmental exposure to nanoparticles (NPs) has significantly increased in the last decades, mostly due to increased environmental pollution and frequent use of NP containing consumer products. Such NPs may enter our body and cause various health-related problems. The brain is a particularly problematic accumulation site due to its physiological and anatomical restrictions. Several mechanisms of NP neurotoxicity have already been identified, however not enough is known especially regarding toxicity of engineered/industrial NPs. The focus of this in vitro study was on analysis of neurotoxicity of different engineered NPs, with which we come into contact in our daily lives; SiO2 NPs, food grade (FG) TiO2 NPs, TiO2 P25 and silver NPs as examples of industrial NPs, and polyacrylic acid (PAA) coated cobalt ferrite NPs as an example of biomedical NPs. All short term exposure experiments (24-72 h) were performed on SH-SY5Y human neuroblastoma cell line in vitro using higher (25-50 µg/ml) as well as lower (2-10 µg/ml), concentrations that are more relevant for in vivo NPs exposure. We show that NPs can cause neurotoxicity through different mechanisms, such as membrane damage, cell cycle interference, ROS formation and accumulation of autophagosomes, depending on their physico-chemical properties and stability in physiological media. Low, in vivo achievable concentrations of NPs induced only minor or no changes in vitro, however prolonged exposure and accumulation in vivo could negatively affect the cells. This was also shown in case of autophagy dysfunction for TiO2 P25 NPs and decrease of cell viability for TiO2 FG NPs, which were only evident after 72 h of incubation.


Assuntos
Nanopartículas/toxicidade , Células-Tronco Neurais/efeitos dos fármacos , Resinas Acrílicas , Autofagossomos/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Membrana Celular/patologia , Sobrevivência Celular , Cobalto , Compostos Férricos , Alimentos , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Síndromes Neurotóxicas/patologia , Espécies Reativas de Oxigênio/metabolismo , Titânio/toxicidade
18.
Biomed Res Int ; 2020: 7380172, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31998797

RESUMO

General anesthetic (GA) is used clinically to millions of young children each year to facilitate surgical procedures, relieve perioperative stress, and provide analgesia and amnesia. During recent years, there is a growing concern regarding a causal association between early life GA exposure and subsequently long-term neurocognitive abnormalities. To address the increasing concern, mounting preclinical studies and clinical trials have been undergoing. Until now, nearly all of the preclinical findings show that neonatal exposure to GA causally leads to acute neural cell injury and delayed cognitive impairment. Unexpectedly, several influential clinical findings suggest that early life GA exposure, especially brief and single exposure, does not cause adverse neurodevelopmental outcome, which is not fully in line with the experimental findings and data from several previous cohort trials. As the clinical data have been critically discussed in previous reviews, in the present review, we try to analyze the potential factors of the experimental studies that may overestimate the adverse effect of GA on the developing brain. Meanwhile, we briefly summarized the advance in experimental research. Generally, our purpose is to provide some useful suggestions for forthcoming preclinical studies and strengthen the powerfulness of preclinical data.


Assuntos
Anestesia Geral/efeitos adversos , Anestésicos Gerais , Encéfalo , Síndromes Neurotóxicas , Anestésicos Gerais/efeitos adversos , Anestésicos Gerais/uso terapêutico , Animais , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Encéfalo/patologia , Criança , Humanos , Neurônios/metabolismo , Neurônios/patologia , Síndromes Neurotóxicas/metabolismo , Síndromes Neurotóxicas/patologia
19.
Neurochem Res ; 45(2): 465-490, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31894463

RESUMO

Protein misfolding and aggregation of amyloid beta (Aß) peptide, as well as formation of neurofibrillary tangles (NFTs) are the signature hallmarks of Alzheimer's disease (AD) pathology. To prevent this, molecular chaperones come into play as they facilitate the refolding of the misfolded proteins and cell protection under stress. Here, we have evaluated the possible effects of Ginkgo biloba (GBE) against aggregation of the Aß through activation of heat shock proteins (HSPs) in the Aluminium (Al) induced AD based model. GBE (100 mg/kg body weight) was administered per oral to the female SD rats in conjunction with intraperitoneal (i.p.) injection of Al lactate (10 mg/kg body weight) for six weeks. Pretreated animals were administered GBE for additional two weeks prior to any exposure of Al. GBE administration resulted in decrease in Aß aggregation, ubiquitin deposition, accompanying a significant decline in APP & Tau protein hyperphosphorylation which can be attributed to activation of Heat shock factor (HSF-1) and upregulation in the protein expression of HSPs. Histopathological investigation studies have also shown the decrease in aggregation of Aß peptide by GBE administration. Additionally, the decrease in ROS levels and Aß aggregation by GBE administration prohibited the decline in the neurotransmitter levels and monoamine oxidase levels in hippocampus and cortex. This further caused improvement in learning and memory of the animals. In conclusion, our results indicate that GBE prevents the symptoms of Al induced AD like pathophysiology by upregulating the HSPs levels and decreasing the aggregation load.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Proteínas de Choque Térmico/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Síndromes Neurotóxicas/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Multimerização Proteica/efeitos dos fármacos , Acetilcolinesterase/metabolismo , Alumínio/toxicidade , Animais , Giro Denteado/patologia , Epinefrina/metabolismo , Feminino , Ginkgo biloba/química , Aprendizagem em Labirinto/efeitos dos fármacos , Monoaminoxidase/metabolismo , Síndromes Neurotóxicas/patologia , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Serotonina/metabolismo , Proteínas tau/metabolismo
20.
Chemosphere ; 238: 124602, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31545211

RESUMO

Polybrominated diphenyl ethers (PBDEs) have been known to exhibit neurotoxicity in rats; however, the underlying mechanism remains unknown and there is no available intervention. In this study, we aimed to investigate the role of oxidative and nitrosative stress in the neurotoxicity in the cerebral cortex and primary neurons in rats following the BDE-153 treatment. Compared to the untreated group, BDE-153 treatment significantly induced the neurotoxic effects in rats, as manifested by the increased lactate dehydrogenase (LDH) activities and cell apoptosis rates, and the decreased neurotrophic factor contents and cholinergic enzyme activities in rats' cerebral cortices and primary neurons. When compared to the untreated group, the oxidative and nitrosative stress had occurred in the cerebral cortex or primary neurons in rats following the BDE-153 treatment, as manifested by the increments in levels of reactive oxygenspecies (ROS), malondialdehyde (MDA), nitric oxide (NO), and neuronal nitric oxide synthase (nNOS) mRNA and protein expressions, along with the decline in levels of superoxide dismutase (SOD) activity, glutathione (GSH) content, and peroxiredoxin I (Prx I) and Prx II mRNA and protein expressions. In addition, the ROS scavenger N-acetyl-l-cysteine (NAC) or NO scavenger NG-Nitro-l-arginine (L-NNA) significantly rescued the LDH leakage and cell survival, reversed the neurotrophin contents and cholinergic enzymes, mainly via regaining balance between oxidation/nitrosation and antioxidation. Overall, our findings suggested that oxidative and nitrosative stresses are involved in the neurotoxicity induced by BDE-153, and that the antioxidation is a potential targeted intervention.


Assuntos
Córtex Cerebral/patologia , Éteres Difenil Halogenados/toxicidade , Síndromes Neurotóxicas/patologia , Estresse Nitrosativo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Bifenil Polibromatos/toxicidade , Acetilcisteína/farmacologia , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Glutationa/metabolismo , Éteres Difenil Halogenados/metabolismo , Masculino , Malondialdeído/metabolismo , Fatores de Crescimento Neural/metabolismo , Neurônios/efeitos dos fármacos , Neurotrofina 3/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo I/metabolismo , Estresse Nitrosativo/fisiologia , Estresse Oxidativo/fisiologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA