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Stroke represents one of the main causes of death and disability in the world; despite this, pharmacological therapies against stroke remain insufficient. Ischemic stroke is the leading etiology of stroke. Different molecular mechanisms, such as excitotoxicity, oxidative stress, and inflammation, participate in cell death and tissue damage. At a preclinical level, different garlic compounds have been evaluated against these mechanisms. Additionally, there is evidence supporting the participation of garlic compounds in other mechanisms that contribute to brain tissue recovery, such as neuroplasticity. After ischemia, neuroplasticity is activated to recover cognitive and motor function. Some garlic-derived compounds and preparations have shown the ability to promote neuroplasticity under physiological conditions and, more importantly, in cerebral damage models. This work describes damage/repair mechanisms and the importance of garlic as a source of antioxidant and anti-inflammatory agents against damage. Moreover, we examine the less-explored neurotrophic properties of garlic, culminating in proposals and observations based on our review of the available information. The aim of the present study is to propose that garlic compounds and preparations could contribute to the treatment of ischemic stroke through their neurotrophic effects.
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Quinolinic acid (QUIN) is an agonist of N-methyl-D-aspartate receptor (NMDAr) used to study the underlying mechanism of excitotoxicity in animal models. There is evidence indicating that impairment in autophagy at early times contributes to cellular damage in excitotoxicity; however, the status of autophagy in QUIN model on day 7 remains unexplored. In this study, the ultrastructural analysis of subcellular compartments and the status of autophagy, necroptosis, and apoptosis in the striatum of rats administered with QUIN (120 nmol and 240 nmol) was performed on day 7. QUIN induced circling behavior, neurodegeneration, and cellular damage; also, it promoted swollen mitochondrial crests, spherical-like morphology, and mitochondrial fragmentation; decreased ribosomal density in the rough endoplasmic reticulum; and altered the continuity of myelin sheaths in axons with separation of the compact lamellae. Furthermore, QUIN induced an increase and a decrease in ULK1 and p-70-S6K phosphorylation, respectively, suggesting autophagy activation; however, the increased microtubule-associated protein 1A/1B-light chain 3-II (LC3-II) and sequestosome-1/p62 (SQSTM1/p62), the coexistence of p62 and LC3 in the same structures, and the decrease in Beclin 1 and mature cathepsin D also indicates a blockage in autophagy flux. Additionally, QUIN administration increased tumor necrosis factor alpha (TNFα) and receptor-interacting protein kinase 3 (RIPK3) levels and its phosphorylation (p-RIPK3), as well as decreased B-cell lymphoma 2 (Bcl-2) and increased Bcl-2-associated X protein (Bax) levels and c-Jun N-terminal kinase (JNK) phosphorylation, suggesting an activation of necroptosis and apoptosis, respectively. These results suggest that QUIN activates the autophagy, but on day 7, it is blocked and organelle and cellular damage, neurodegeneration, and behavior alterations could be caused by necroptosis and apoptosis activation.
Assuntos
Ácido Quinolínico , Fator de Necrose Tumoral alfa , Animais , Apoptose/fisiologia , Autofagia/fisiologia , Proteína Beclina-1/metabolismo , Catepsina D/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Lisossomos/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Necroptose , Ácido Quinolínico/toxicidade , Ratos , Receptores de N-Metil-D-Aspartato/metabolismo , Proteína Sequestossoma-1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
Tuberculosis (TB) is one of the ten leading causes of death worldwide. Patients with TB have been observed to suffer from depression and anxiety linked to social variables. Previous experiments found that the substantial pulmonary inflammation associated with TB causes neuroinflammation, neuronal death, and behavioral impairments in the absence of brain infection. Curcumin (CUR) is a natural product with antioxidant, anti-inflammatory and antibacterial activities. In this work, we evaluated the CUR effect on the growth control of mycobacteria in the lungs and the anti-inflammatory effect in the brain using a model of progressive pulmonary TB in BALB/c mice infected with drug-sensitive mycobacteria (strain H37Rv). The results have shown that CUR decreased lung bacilli load and pneumonia of infected animals. Finally, CUR significantly decreased neuroinflammation (expression of TNFα, IFNγ and IL12) and slightly increased the levels of nuclear factor erythroid 2-related to factor 2 (Nrf2) and the brain-derived neurotrophic factor (BDNF) levels, improving behavioral status. These results suggest that CUR has a bactericidal effect and can control pulmonary mycobacterial infection and reduce neuroinflammation. It seems that CUR has a promising potential as adjuvant therapy in TB treatment.
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Anti-Inflamatórios/farmacologia , Antituberculosos/farmacologia , Encéfalo/microbiologia , Curcumina/farmacologia , Pulmão/microbiologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose/tratamento farmacológico , Animais , Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose/metabolismo , Tuberculose Pulmonar/metabolismoRESUMO
Garlic (Allium sativum) has been used in alternative medicine to treat several diseases, such as cardiovascular and neurodegenerative diseases, cancer, and hepatic diseases. Several publications have highlighted other features of garlic, including its antibacterial, antioxidative, antihypertensive, and antithrombotic properties. The properties of garlic result from the combination of natural compounds that act synergistically and cause different effects. Some garlic-derived compounds have been studied for the treatment of several types of cancer; however, reports on the effects of garlic on neuroblastoma are scarce. Neuroblastoma is a prevalent childhood tumor for which the search for therapeutic alternatives to improve treatment without affecting the patients' quality of life continues. Garlic-derived compounds hold potential for the treatment of this type of cancer. A review of articles published to date on some garlic compounds and their effect on neuroblastoma was undertaken to comprehend the possible therapeutic role of these compounds. This review aimed to analyze the impact of some garlic compounds on cells derived from neuroblastoma.
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Tuberculosis (TB) is a chronic infectious disease in which prolonged, non-resolutive inflammation of the lung may lead to metabolic and neuroendocrine dysfunction. Previous studies have reported that individuals coursing pulmonary TB experience cognitive or behavioural changes; however, the pathogenic substrate of such manifestations have remained unknown. Here, using a mouse model of progressive pulmonary TB, we report that, even in the absence of brain infection, TB is associated with marked increased synthesis of both inflammatory and anti-inflammatory cytokines in discrete brain areas such as the hypothalamus, the hippocampal formation and cerebellum accompanied by substantial changes in the synthesis of neurotransmitters. Moreover, histopathological findings of neurodegeneration and neuronal death were found as infection progressed with activation of p38, JNK and reduction in the BDNF levels. Finally, we perform behavioural analysis in infected mice throughout the infection, and our data show that the cytokine and neurochemical changes were associated with a marked onset of cognitive impairment as well as depressive- and anxiety-like behaviour. Altogether, our results suggest that besides pulmonary damage, TB is accompanied by an extensive neuroinflammatory and neurodegenerative state which explains some of the behavioural abnormalities found in TB patients.
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Encéfalo/metabolismo , Disfunção Cognitiva/metabolismo , Citocinas/metabolismo , Inflamação/metabolismo , Mycobacterium tuberculosis/metabolismo , Neurônios/patologia , Tuberculose Pulmonar/metabolismo , Animais , Ansiedade/metabolismo , Ansiedade/microbiologia , Sintomas Comportamentais/microbiologia , Barreira Hematoencefálica/citologia , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Encéfalo/citologia , Encéfalo/enzimologia , Encéfalo/patologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cromatografia Líquida de Alta Pressão , Disfunção Cognitiva/microbiologia , Depressão/metabolismo , Depressão/microbiologia , Modelos Animais de Doenças , Regulação para Baixo , Hipocampo/citologia , Hipocampo/imunologia , Hipocampo/metabolismo , Hipocampo/patologia , Janus Quinases/metabolismo , Sistema de Sinalização das MAP Quinases/genética , Masculino , Camundongos Endogâmicos BALB C , Mycobacterium tuberculosis/patogenicidade , Neurônios/citologia , Neurotransmissores/metabolismo , Tuberculose Pulmonar/enzimologia , Tuberculose Pulmonar/patologia , Tuberculose Pulmonar/psicologia , Regulação para Cima , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Depression is a psychiatric disorder, and oxidative stress is a significant mechanism of damage in this mood disorder. It is characterized by an enhancement of oxidative stress markers and low concentrations of endogenous antioxidants, or antioxidants enzymes. This suggests that antioxidants could have an antidepressant effect. S-allyl cysteine (SAC) is a compound with antioxidant action or free radical scavenger capacity. The purpose of the current research was to evaluate the antidepressant-like effect as well as the antioxidant role of SAC on a preclinical test, using the Porsolt forced swim test (FST). SAC (30, 70, 120, or 250 mg/kg, ip) was administered to male BALB/c mice daily for 17 days, followed by the FST at day 18. Oxidative stress markers (reactive oxygen species, superoxide production, lipid peroxidation, and antioxidant enzymes activities) were analyzed in the midbrain, prefrontal cortex, and hippocampus. SAC (120 mg/kg) attenuated the immobility scores (44%) in the FST, and protection was unrelated to changes in locomotor activity. This antidepressant-like effect was related to decreased oxidative stress, as indicated by lipid peroxidation and manganese-superoxide dismutase (Mn-SOD) activity in the hippocampus. SAC exerts an antidepressant-like effect that correlated, in part, with preventing oxidative damage in hippocampus.
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Currently, chronic liver diseases have conditioned morbidity and mortality, many of these with a metabolic, toxicologic, immunologic, viral, or other etiology. Thus, a transcription factor that has been of huge importance for biomedical research is NRF-2. The latter is considered a principal component of the antioxidant mechanism, and it has been acknowledged that it impairs the function of NRF-2 in many liver diseases and that it forms an essential part of the pathologic changes that occur in the liver to contain inflammation and damage. Within the investigations and experiments carried out, there are isolated drugs, many of them related to plants and natural extracts that possess antioxidant properties through the NRF-2 signaling pathway, or even involving the stimulation of the transcription target proteins of NRF-2. Notwithstanding all of these experimental findings, to date there is not sufficient clinical evidence to justify the use of NRF-2 in medical practice.
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Fígado/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estresse Oxidativo , Animais , Antioxidantes/uso terapêutico , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Fator 2 Relacionado a NF-E2/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/patologia , Estresse Oxidativo/efeitos dos fármacos , Transdução de SinaisRESUMO
Stroke is a public health problem due to its high mortality and disability rates; despite these, the pharmacological treatments are limited. Oxidative stress plays an important role in cerebral damage in stroke and the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) confers protection against oxidative stress. Different compounds, such as diallyl trisulfide (DATS), have the ability to activate Nrf2. DATS protects against the damage induced in oxygen-glucose deprivation in neuronal cells; however, in in vivo models of cerebral ischemia, DATS has not been evaluated. Male Wistar rats were subjected to 1 h of ischemia and seven days of reperfusion and the protective effect of DATS was evaluated. DATS administration (IR + DATS) decreased the infarct area and brain damage in the striatum and cortex; improved neurological function; decreased malondialdehyde and metalloproteinase-9 levels; increased Nrf2 activation in the cortex and the expression of superoxide dismutase 1 (SOD1) in the nucleus, SOD2 and glutathione S-transferase (GST) in the striatum and cortex; and increased the activity of catalase (CAT) in the striatum and glutathione peroxidase (GPx) in the cortex. Our results demonstrate the protective effect of DATS in an in vivo model of cerebral ischemia that involves Nrf2 activation.
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In the present study we investigated the participation of brain-derived neurotropic factor (BDNF) on the activation of the mitogen activated protein kinase (MAPK) protein extracellular signal-regulated kinase-1/2 (ERK1/2) as a mechanism of curcumin (CUR) to provide an antioxidant defense system mediated by the nuclear factor erythroid 2-related factor 2 (Nrf2) in the neurotoxic model induced by quinolinic acid (QUIN). Wistar rats received CUR (400 mg/kg, intragastrically) for 6 days after intrastriatal injection with QUIN (240 nmol). CUR improved the motor deficit and morphological alterations induced by QUIN and restored BDNF, ERK1/2, and Nrf2 levels. CUR treatment avoided the decrease in the protein levels of glutathione peroxidase (GPx), glutathione reductase (GR), γ-glutamylcysteine ligase (γ-GCL), and glutathione (GSH) levels. Only, the QUIN-induced decrease in the GR activity was prevented by CUR treatment. Finally, QUIN increased superoxide dismutase 2 (SOD2) and catalase (CAT) levels, and the γGCL and CAT activities; however, this increase was major in the QUIN+CUR group for γ-GCL, CAT, and SOD activities. These data suggest that the therapeutic effect of CUR could involve BDNF action on the activation of ERK1/2 to induce increased levels of protein and enzyme activity of antioxidant proteins regulated by Nrf2 and GSH levels.
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Doenças do Sistema Nervoso/prevenção & controle , Cálcio/metabolismo , Retículo Endoplasmático/metabolismo , Metabolismo Energético , Humanos , Doenças do Sistema Nervoso/metabolismo , Doenças do Sistema Nervoso/patologia , Fármacos Neuroprotetores/uso terapêutico , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Vitamina D/uso terapêuticoRESUMO
Nuclear Factor Erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates the expression of genes involved in the metabolism, immune response, cellular proliferation, and other processes; however, the attention has been focused on the study of its ability to induce the expression of proteins involved in the antioxidant defense. Nrf2 is mainly regulated by Kelch-like ECH-associated protein 1 (Keap1), an adapter substrate of Cullin 3 (Cul3) ubiquitin E3 ligase complex. Keap1 represses Nrf2 activity in the cytoplasm by its sequestering, ubiquitination and proteosomal degradation. Nrf2 activation, through the canonical mechanism, is carried out by electrophilic compounds and oxidative stress where some cysteine residues in Keap1 are oxidized, resulting in a decrease in Nrf2 ubiquitination and an increase in its nuclear translocation and activation. In the nucleus, Nrf2 induces a variety of genes involved in the antioxidant defense. Recently a new mechanism of Nrf2 activation has been described, called the non-canonical pathway, where proteins such as p62, p21, dipeptidyl peptidase III (DPP3), wilms tumor gene on X chromosome (WTX) and others are able to disrupt the Nrf2-Keap1 complex, by direct interaction with Keap1 decreasing Nrf2 ubiquitination and increasing its nuclear translocation and activation. In this review, the regulatory mechanisms involved in both canonical and non-canonical Nrf2 activation are discussed.
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Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Transporte Ativo do Núcleo Celular , Animais , Regulação da Expressão Gênica , Humanos , Fator 2 Relacionado a NF-E2/genética , Oxirredução , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , Transdução de Sinais , UbiquitinaçãoRESUMO
Oxidative stress secondary to excitotoxicity is a common factor in the physiopathology of a variety of neurological disorders. In response to oxidative stress, several signaling pathways, such as MAPK, are activated or inactivated. Mitogen-activated protein kinase (MAPK) family activation must be finely regulated in time and intensity, as this pathway may either preserve cell survival or promote cell death. In the present study, the activation of MAPK in the excitotoxic injury induced by quinolinic acid (QUIN) was examined in vivo, at short and long times. We used different doses (30, 60, 120 and 240â¯nmol) of QUIN injected intrastriatally in the right rat striatum and the effect of this treatment on motor deficits, cellular damage, MAPK activation and BDNF/TrkB axis, were evaluated at 2â¯h and 7â¯days post-lesion. Higher doses of QUIN (120 and 240â¯nmol) induced rat motor deficits and caused morphological changes in neurons around the lesion core. QUIN decreased the activation of ERK1/2 in a dose-dependent manner at 7â¯days post-injection, and induced a sustained increase of c-Jun NH2-terminal kinase (JNK) activation from 2â¯h to 7â¯days post-injury. JNK activation was dependent on the QUIN-induced NMDAr activation (only 120â¯nmol). No significant difference in p38 activation with QUIN was observed. QUIN (120 and 240â¯nmol) decreased BDNF/TrkB levels at 7â¯days post-injury. JNK inhibition (by an intracerebroventricular injection of SP600125) prevented the QUIN-induced reduction in BDNF and TrkB at 7â¯day post-injury, suggesting a role for the QUIN-induced JNK activation on the observed decrease in BDNF levels.
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Fator Neurotrófico Derivado do Encéfalo/metabolismo , Corpo Estriado/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Ácido Quinolínico/toxicidade , Receptor trkB/metabolismo , Animais , Corpo Estriado/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Estresse Oxidativo/fisiologia , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologiaRESUMO
The original version of this article unfortunately contained a mistake.
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Cadmium (Cd) is a trace metal without essential biological functions that is toxic to plants, animals and humans at low concentrations. It occurs naturally in soils, but inputs from anthropogenic sources have increased soil Cd contents worldwide. Cadmium uptake by cocoa (Theobroma cacao L.) has recently attracted attention, after the European Union (EU) decided to bring into force values for maximum Cd concentrations in cocoa products that would be exceeded by current products of various provenances from Latin America. In order to identify factors governing Cd uptake by cocoa, we carried out a survey on 55 cocoa farms in Honduras in which we determined Cd concentrations in cocoa leaves, pod husks and beans and analysed their relationships to a variety of surrounding soil and site factors. Averaging 2.6±0.4mgkg-1, the concentrations of Cd were higher in the leaves than in the beans. With an average of 1.1±0.2mgkg-1, the bean Cd concentrations still exceeded the proposed EU limit, however. The bean Cd showed large differences between geological substrates, even though regional variations in 'total' soil Cd were comparably small and the average concentration was in the range of uncontaminated soils (0.25±0.02mgkg-1). As we found no influence of fertilizer application or vicinity to industrial sites, we conclude that the differences in soil Cd between sites were due to natural variation. Of all factors included here, DGT-available soil Cd was the best predictor of bean Cd (R2=0.5). When DGT was not considered, bean Cd was best predicted by 'total' soil Cd, pH and geology. The highest bean Cd concentrations were found on alluvial substrates.
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Cacau/metabolismo , Cádmio/metabolismo , Poluentes do Solo/metabolismo , Solo/química , HondurasRESUMO
Oxidative stress plays an important role in neurodegenerative diseases and aging. The cellular defense mechanisms to deal with oxidative damage involve the activation of transcription factor related to NF-E2 (Nrf2), which enhances the transcription of antioxidant and phase II enzyme genes. S-allylcysteine (SAC) is an antioxidant with neuroprotective properties, and the main organosulfur compound in aged garlic extract. The ability of SAC to activate the Nrf2 factor has been previously reported in hepatic cells; however this effect has not been studied in normal brain. In order to determine if the chronic administration of SAC is able to activate Nrf2 factor and enhance antioxidant defense in the brain, male Wistar rats were administered with SAC (25, 50, 100 and 200 mg/kg-body weight each 24 h, i.g.) for 90 days. The activation of Nrf2, the levels of p65 and 8-hydroxy-2-deoxyguanosine (8-OHdG) as well as the activities of the enzymes glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), superoxide dismutase (SOD), and glutathione S-transferase (GST) were evaluated in the hippocampus, striatum and frontal cortex. Results showed that SAC activated Nrf2 factor in the hippocampus (25-200 mg/kg) and striatum (100 mg/kg) and significantly decreased p65 levels in the frontal cortex (25-200 mg/kg). On the other hand, SAC increased GPx, GR, CAT and SOD activities mainly in the hippocampus and striatum, but it did not change GST activity. Finally, no changes were observed in 8-OHdG levels mediated by SAC in any brain region, but the hippocampus showed a major level of 8-OHdG compared with the striatum and frontal cortex. All these results suggest that in the hippocampus, the observed increase in the activity of antioxidant enzymes could be associated with the ability of SAC to activate Nrf2 factor; however, a different mechanism could be involved in the striatum and frontal cortex, since no changes were found in Nrf2 activation and p65 levels.
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Antioxidantes/metabolismo , Corpo Estriado/metabolismo , Cisteína/análogos & derivados , Lobo Frontal/metabolismo , Hipocampo/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Corpo Estriado/efeitos dos fármacos , Cisteína/administração & dosagem , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Lobo Frontal/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Masculino , Ratos , Ratos WistarRESUMO
BACKGROUND: Aged garlic extract (AGE) and its main constituent S-allylcysteine (SAC) are natural antioxidants with protective effects against cerebral ischemia or cancer, events that involve hypoxia stress. Cobalt chloride (CoCl2) has been used to mimic hypoxic conditions through the stabilization of the α subunit of hypoxia inducible factor (HIF-1α) and up-regulation of HIF-1α-dependent genes as well as activation of hypoxic conditions such as reactive oxygen species (ROS) generation, loss of mitochondrial membrane potential and apoptosis. The present study was designed to assess the effect of AGE and SAC on the CoCl2-chemical hypoxia model in PC12 cells. RESULTS: We found that CoCl2 induced the stabilization of HIF-1α and its nuclear localization. CoCl2 produced ROS and apoptotic cell death that depended on hypoxia extent. The treatment with AGE and SAC decreased ROS and protected against CoCl2-induced apoptotic cell death which depended on the CoCl2 concentration and incubation time. SAC or AGE decreased the number of cells in the early and late stages of apoptosis. Interestingly, this protective effect was associated with attenuation in HIF-1α stabilization, activity not previously reported for AGE and SAC. CONCLUSIONS: Obtained results show that AGE and SAC decreased apoptotic CoCl2-induced cell death. This protection occurs by affecting the activity of HIF-1α and supports the use of these natural compounds as a therapeutic alternative for hypoxic conditions.
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Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/efeitos dos fármacos , Cisteína/análogos & derivados , Alho/química , Extratos Vegetais/farmacologia , Análise de Variância , Animais , Hipóxia Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cobalto , Cisteína/farmacologia , Citometria de Fluxo , Formazans , Células PC12 , Ratos , Espécies Reativas de Oxigênio/análise , Sais de TetrazólioRESUMO
BACKGROUND: Aged garlic extract (AGE) and its main constituent S-allylcysteine (SAC) are natural antioxidants with protective effects against cerebral ischemia or cancer, events that involve hypoxia stress. Cobalt chloride (CoCl2) has been used to mimic hypoxic conditions through the stabilization of the α subunit of hypoxia inducible factor (HIF-1α) and up-regulation of HIF-1α-dependent genes as well as activation of hypoxic conditions such as reactive oxygen species (ROS) generation, loss of mitochondrial membrane potential and apoptosis. The present study was designed to assess the effect of AGE and SAC on the CoCl2-chemical hypoxia model in PC12 cells. RESULTS: We found that CoCl2 induced the stabilization of HIF-1α and its nuclear localization. CoCl2 produced ROS and apoptotic cell death that depended on hypoxia extent. The treatment with AGE and SAC decreased ROS and protected against CoCl2-induced apoptotic cell death which depended on the CoCl2 concentration and incubation time. SAC or AGE decreased the number of cells in the early and late stages of apoptosis. Interestingly, this protective effect was associated with attenuation in HIF-1α stabilization, activity not previously reported for AGE and SAC. CONCLUSIONS: Obtained results show that AGE and SAC decreased apoptotic CoCl2-induced cell death. This protection occurs by affecting the activity of HIF-1α and supports the use of these natural compounds as a therapeutic alternative for hypoxic conditions
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Animais , Ratos , Extratos Vegetais/farmacologia , Apoptose/efeitos dos fármacos , Cisteína/análogos & derivados , Fatores de Transcrição Hélice-Alça-Hélice Básicos/efeitos dos fármacos , Alho/química , Antioxidantes/farmacologia , Sais de Tetrazólio , Hipóxia Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Análise de Variância , Células PC12 , Espécies Reativas de Oxigênio/análise , Cobalto , Cisteína/farmacologia , Citometria de Fluxo , FormazansRESUMO
The oxidative stress state is characterized by an increase in oxygen reactive species that overwhelms the antioxidant defense; we do not know if these pathological changes are correlated with alterations in left ventricular mechanics. The aim was correlating the oxidative stress state with the left ventricular global longitudinal strain (GLS) and the left ventricular end diastolic pressure (LVEDP). Twenty-five patients with essential hypertension and 25 controls paired by age and gender were studied. All of the participants were subjected to echocardiography and biochemical determination of oxidative stress markers. The hypertensive patients, compared with control subjects, had significantly (p < 0.05) higher levels of oxidized proteins (5.03 ± 1.05 versus 4.06 ± 0.63 nmol/mg), lower levels of extracellular superoxide dismutase (EC-SOD) activity (0.045 ± 0.02 versus 0.082 ± 0.02 U/mg), higher LVEDP (16.2 ± 4.5 versus 11.3 ± 1.6 mm Hg), and lower GLS (-12% versus -16%). Both groups had preserved ejection fraction and the results showed a positive correlation of oxidized proteins with GLS (r = 0.386, p = 0.006) and LVEDP (r = 0.389, p = 0.005); we also found a negative correlation of EC-SOD activity with GLS (r = -0.404, p = 0.004) and LVEDP (r = -0.347, p = 0.014).
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Ventrículos do Coração/fisiopatologia , Hipertensão/patologia , Estresse Oxidativo , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Hipertensão Essencial , Feminino , Ventrículos do Coração/diagnóstico por imagem , Humanos , Hipertensão/metabolismo , Masculino , Pessoa de Meia-Idade , Superóxido Dismutase/sangue , Ultrassonografia , Função Ventricular Esquerda/fisiologiaRESUMO
AIMS: This simple study was designed to investigate whether acute restraint stress can generate changes in behavioral tests and hippocampal endpoints of oxidative stress in rats, and if the antioxidant S-allyl cysteine (SAC) can prevent these alterations. MATERIALS AND METHODS: We evaluated motor activity, forced swimming and anxiety behavior, as well as the hippocampal levels of lipid peroxidation and the activities of glutathione-related enzymes in animals submitted to mild immobilization. The effect of SAC (100 mg/kg, i.p.), given to rats every day 30 min before starting the immobilization session, was also investigated. Immobilization (restraint) stress was induced for a period of 6 h per day for five consecutive days. KEY FINDINGS: Our results indicate that, under the tested conditions, acute restraint stimulates compensatory behavioral tasks (motor activity, anxiety and forced swimming) to counteract the stressing conditions prevailing, and selectively increased the levels of lipid peroxidation and the enzyme activities of glutathione-S-transferase (GST) and glutathione peroxidase (GPx) in the hippocampus also as adaptive responses. SAC exhibited preventive effects in the stressed group as it improved behavior, reduced lipid peroxidation and prevented the increase of GST and GPx activities, suggesting that this antioxidant blunted primary pro-oxidative stimuli induced by restraint stress. SIGNIFICANCE: Findings of this work also confirm that the use of antioxidants such as SAC can provide effective protection against the acute oxidative damage associated with anxiety produced by stressing conditions.