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BACKGROUND: Blackcurrant (Ribes nigrum L.) is a berry rich in anthocyanins, bioactive compounds known for their antioxidant and neuroprotective properties that benefit human health. AIMS: This study aimed to investigate the effects of blackcurrant and its association with Donepezil on memory impairment, cholinergic neurotransmission, and antioxidant systems in a mouse model of amnesia induced by chronic administration of Scopolamine. METHODS: Adult male Swiss mice were given saline, blackcurrant (50 mg/kg, orally), and/or Donepezil (5 mg/kg, orally) and/or Scopolamine (1 mg/kg, intraperitoneally). RESULTS: Behavioral tests revealed that blackcurrant and/or Donepezil prevented the learning and memory deficits induced by Scopolamine. In the cerebral cortex and hippocampus, blackcurrant and/or Donepezil treatments prevented the increase in acetylcholinesterase and butyrylcholinesterase activities induced by Scopolamine. Scopolamine also disrupted the glutathione redox system and increased levels of reactive species; nevertheless, blackcurrant and/or Donepezil treatments were able to prevent oxidative stress. Furthermore, these treatments prevented the increase in gene expression and protein density of acetylcholinesterase and the decrease in gene expression of the choline acetyltransferase enzyme induced by Scopolamine. CONCLUSIONS: Findings suggest that blackcurrant and Donepezil, either alone or in combination, have anti-amnesic effects by modulating cholinergic system enzymes and improving the redox profile. Therefore, blackcurrant could be used as a natural supplement for the prevention and treatment of memory impairment in neurodegenerative diseases.
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Resistance exercise training (RET) is considered an excellent tool for preventing diseases with an inflammatory background. Its neuroprotective, antioxidant, and anti-inflammatory properties are responsible for positively modulating cholinergic and oxidative systems, promoting neurogenesis, and improving memory. However, the mechanisms behind these actions are largely unknown. In order to investigate the pathways related to these effects of exercise, we conducted a 12-week long-term exercise training protocol and used lipopolysaccharide (LPS) to induce damage to the cortex and hippocampus of male Wistar rats. The cholinergic system, oxidative stress, and histochemical parameters were analyzed in the cerebral cortex and hippocampus, and memory tests were also performed. It was observed that LPS: (1) caused memory loss in the novel object recognition (NOR) test; (2) increased the activity of acetylcholinesterase (AChE) and Iba1 protein density; (3) reduced the protein density of brain-derived neurotrophic factor (BDNF) and muscarinic acetylcholine receptor M1 (CHRM1); (4) elevated the levels of lipid peroxidation (TBARS) and reactive species (RS); and (5) caused inflammatory damage to the dentate gyrus. RET, on the other hand, was able to prevent all alterations induced by LPS, as well as increase per se the protein density of the alpha-7 nicotinic acetylcholine receptor (nAChRα7) and Nestin, and the levels of protein thiols (T-SH). Overall, our study elucidates some mechanisms that support resistance physical exercise as a valuable approach against LPS-induced neuroinflammation and memory loss.
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Lipopolisacáridos , Trastornos de la Memoria , Enfermedades Neuroinflamatorias , Condicionamiento Físico Animal , Ratas Wistar , Animales , Masculino , Lipopolisacáridos/toxicidad , Condicionamiento Físico Animal/fisiología , Condicionamiento Físico Animal/métodos , Ratas , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/inducido químicamente , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/metabolismo , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Entrenamiento de Fuerza/métodos , Corteza Cerebral/metabolismo , Corteza Cerebral/efectos de los fármacos , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Acetilcolinesterasa/metabolismo , Receptor Muscarínico M1/metabolismoRESUMEN
This study investigated the neuroprotective effects of exendin-4 (EXE-4), an analog of the glucagon-like peptide 1 receptor (GLP-1R) on memory and on the neuronal populations that constitute the hippocampus of rats submitted to a sporadic dementia of Alzheimer's type (SDAT). Male Wistar rats received streptozotocin (STZ icv, 3 mg/kg diluted in aCFS, 5 µl/ventricle) and were treated for 21 days with EXE-4 (10 µg/kg, ip; saline as the vehicle). Four groups were formed: vehicle, EXE-4, STZ, and STZ + EXE-4. The groups were submitted to Y-Maze (YM), object recognition (ORT), and object displacement tasks (ODT) to assess learning and memory. The brains were used for immunohistochemical and immunofluorescent techniques with antibodies to NeuN, cleaved caspase-3 (CC3), PCNA, doublecortin (DCX), synaptophysin (SYP), and insulin receptor (IR). STZ worsened spatial memory in the YMT, as well as short-term (STM) and long-term (LTM) memories in the ORT and ODT, respectively. EXE-4 protected against memory impairment in STZ animals. STZ reduced mature neuron density (NeuN) and increased cell apoptosis (CC3) in the DG, CA1, and CA3. EXE-4 protected against neuronal death in all regions. EXE-4 increased PCNA+ cells in all regions of the hippocampus, and STZ attenuated this effect. STZ reduced neurogenesis in DG per se as well as synaptogenesis induced by EXE-4. EXE-4 increased immunoreactivity to IR in the CA1. From these findings, EXE-4 showed a beneficial effect on hippocampal pyramidal and granular neurons in the SDAT showing anti-apoptotic properties and promoting cell proliferation. In parallel, EXE-4 preserved the memory of SDAT rats. EXE-4 appears to enhance synapses at CA3 and DG. In conclusion, these data indicate that agonists to GLP-1R have a beneficial effect on hippocampal neurons in AD.
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This study aimed to analyze whether taurine has a nootropic effect on short-term and long-term memory in a model of sporadic dementia of the Alzheimer's type (SDAT). Moreover, we evaluated the immunoreactivity and insulin receptor (IR) distribution and markers for neurons and glial cells in the hippocampus of rats with SDAT and treated with taurine. For this, Male Wistar rats received STZ (ICV, 3 mg/kg, bilateral, 5ul per site, aCFS vehicle) and were treated with taurine (100 mg/kg orally, 1 time per day, saline vehicle) for 25 days. The animals were divided into 4 groups: vehicle (VE), taurine (TAU), ICV-STZ (STZ) and ICV-STZ plus taurine (STZ + TAU). At the end of taurine treatment, short- and long-term memory were assessed by performance on object recognition and Y-maze tasks. Insulin receptor (IR) was evaluated by immunoperoxidase while mature neurons (NeuN), astrocytes (GFAP, S100B, SOX9), and microglia (Iba-1) were evaluated by immunofluorescence. STZ induced worse spatial and recognition memory (INDEX) in YM and ORT tasks. Taurine protected against STZ-induced memory impairment. SDAT reduced the population of mature neurons as well as increased astrocytic and microglial reactivity, and taurine protected against these STZ-induced effects, mainly in the CA1 region of the hippocampus. Taurine increases IR expression in the hippocampus, and protects against the reduction in the density of this receptor in CA1 induced by STZ. In conclusion, these findings demonstrate that taurine is able to enhance memory, up-regulates IR in the hippocampus, protects the neuron population, and reduces the astrogliosis found in SDAT.
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The aim of this study was to investigate the ability of tannic acid (TA) in preventing memory deficits and neurochemical alterations observed in a model for Sporadic Dementia of Alzheimer's Type. Rats were treated with TA (30 mg/kg) daily for 21 days, and subsequently received intracerebroventricular injection of streptozotocin (STZ). We observed that STZ induced learning and memory impairments; however, treatment with TA was able to prevent these effects. In cerebral cortex and hippocampus, STZ induced an increase in acetylcholinesterase activity, reduced Na+, K+-ATPase activity and induced oxidative stress increasing thiobarbituric acid-reactive substances, nitrites and reactive oxygen species levels and reducing the activity of antioxidant enzymes. Treatment with TA was able in prevent the major of these neurochemical alterations. In conclusion, TA prevented memory deficits, alterations in brain enzyme activities, and oxidative damage induced by STZ. Thus, TA can be an interesting strategy in the prevention of Sporadic Alzheimer's Disease.
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Enfermedad de Alzheimer , Acetilcolinesterasa/metabolismo , Adenosina Trifosfatasas , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/prevención & control , Animales , Modelos Animales de Enfermedad , Aprendizaje por Laberinto , Oxidación-Reducción , Estrés Oxidativo , Ratas , Ratas Wistar , Estreptozocina/toxicidad , TaninosRESUMEN
This study investigated the effects of inosine on memory acquisition and consolidation, cholinesterases activities, redox status and Na+, K+-ATPase activity in a rat model of scopolamine-induced cognitive impairment. Adult male rats were divided into four groups: control (saline), scopolamine (1 mg/kg), scopolamine plus inosine (50 mg/kg), and scopolamine plus inosine (100 mg/kg). Inosine was pre-administered for 7 days, intraperitoneally. On day 8, scopolamine was administered pre (memory acquisition protocol) or post training (memory consolidation protocol) on inhibitory avoidance tasks. The animals were subjected to the step-down inhibitory avoidance task 24 hours after the training. Scopolamine induced impairment in the acquisition and consolidation phases; however, inosine was able to prevent only the impairment in memory consolidation. Also, scopolamine increased the activity of acetylcholinesterase and reduced the activity of Na+, K+-ATPase and the treatment with inosine protected against these alterations in consolidation protocol. In the animals treated with scopolamine, inosine improved the redox status by reducing the levels of reactive oxygen species and thiobarbituric acid reactive substances and restoring the activity of the antioxidant enzymes, superoxide dismutase and catalase. Our findings suggest that inosine may offer protection against scopolamine-induced memory consolidation impairment by modulating brain redox status, cholinergic signaling and ion pump activity. This compound may provide an interesting approach in pharmacotherapy and as a prophylactic against neurodegenerative mechanisms involved in Alzheimer's disease.
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Disfunción Cognitiva , Consolidación de la Memoria , Acetilcolinesterasa/metabolismo , Animales , Colinérgicos/efectos adversos , Inosina/efectos adversos , Bombas Iónicas/farmacología , Bombas Iónicas/uso terapéutico , Masculino , Aprendizaje por Laberinto , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/prevención & control , Oxidación-Reducción , Estrés Oxidativo , Ratas , Ratas Wistar , Escopolamina/farmacologíaRESUMEN
Alzheimer's disease (AD) is a neurodegenerative pathology characterized by progressive impairment of memory, associated with neurochemical alterations and limited therapy. The aim of this study was to evaluate the effects of inosine on memory, neuroinflammatory cytokines, neurotrophic factors, expression of purinergic receptors, and morphological changes in the hippocampus and cerebral cortex of the rats with AD induced by streptozotocin (STZ). Male rats were divided into four groups: I, control; II, STZ; III, STZ plus inosine (50 mg/kg); and IV, STZ plus inosine (100 mg/kg). The animals received intracerebroventricular injections of STZ or buffer. Three days after the surgical procedure, animals were treated with inosine (50 mg/kg or 100 mg/kg) for 25 days. Inosine was able to prevent memory deficits and decreased the immunoreactivity of the brain A2A adenosine receptor induced by STZ. Inosine also increased the levels of brain anti-inflammatory cytokines (IL-4 and IL-10) and the expression of brain-derived neurotrophic factor and its receptor. Changes induced by STZ in the molecular layer of the hippocampus were attenuated by treatment with inosine. Inosine also protected against the reduction of immunoreactivity for synaptophysin induced by STZ in CA3 hippocampus region. However, inosine did not prevent the increase in GFAP in animals exposed to STZ. In conclusion, our findings suggest that inosine has therapeutic potential for AD through the modulation of different brain mechanisms involved in neuroprotection.
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Enfermedad de Alzheimer , Inosina , Receptores Purinérgicos , Enfermedad de Alzheimer/metabolismo , Animales , Encéfalo/metabolismo , Modelos Animales de Enfermedad , Hipocampo/metabolismo , Inosina/farmacología , Inosina/uso terapéutico , Masculino , Aprendizaje por Laberinto , Trastornos de la Memoria/tratamiento farmacológico , Enfermedades Neuroinflamatorias , Ratas , Ratas Wistar , Receptores Purinérgicos/metabolismo , EstreptozocinaRESUMEN
The present study investigated the neuroprotective effect of taurine against the deleterious effects of chronic-recurrent neuroinflammation induced by LPS in the cerebellum of rats. Adult male Wistar rats were treated with taurine for 28 days. Taurine was administered at a dose of 30 or 100 mg/kg, by gavage. On days 7, 14, 21, and 28, the animals received LPS (250 µg/kg) intraperitoneally. The vehicle used was saline. The animals were divided into six groups: vehicle, taurine 30 mg/kg, taurine 100 mg/kg, LPS, LPS plus taurine 30 mg/kg, and LPS plus taurine 100 mg/kg. On day 29, the animals were euthanized, and the cerebellum was removed and prepared for immunofluorescence analysis using antibodies of GFAP, NeuN, CD11b, and cleaved caspase-3. LPS group showed a reduction in the immunoreactivity of GFAP in the arbor vitae and medullary center and of NeuN in the granular layer of the cerebellar cortex. LPS increased the immunoreactivity of CD11b in the arbor vitae and in the medullary center. Taurine protected against these effects induced by LPS in immunoreactivity of GFAP, NeuN, and CD11b, with the 100 mg/kg dose being the most effective. LPS induced an increase in the number of positive cleaved caspase-3 cells in the Purkinje cell layers, granular layer, arbor vitae, and medullary center. Taurine showed its antiapoptotic activity by reducing the cleaved caspase-3 cells in relation to the LPS group. Here, a potential neuroprotective role of taurine can be seen since this amino acid was effective in protecting the cerebellum of rats against cell death and changes in glial and neuronal cells in the face of chronic-recurrent neuroinflammation.
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Cerebelo/efectos de los fármacos , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Taurina/farmacología , Animales , Apoptosis/efectos de los fármacos , Apoptosis/inmunología , Caspasa 3/análisis , Caspasa 3/metabolismo , Cerebelo/inmunología , Cerebelo/patología , Enfermedad Crónica , Modelos Animales de Enfermedad , Humanos , Lipopolisacáridos/administración & dosificación , Lipopolisacáridos/inmunología , Masculino , Microglía/efectos de los fármacos , Microglía/inmunología , Microglía/patología , Enfermedades Neuroinflamatorias/inmunología , Neuronas/efectos de los fármacos , Neuronas/inmunología , Neuronas/patología , Fármacos Neuroprotectores/uso terapéutico , Ratas , Ratas Wistar , Recurrencia , Taurina/uso terapéuticoRESUMEN
Growing evidence suggests that drugs targeting neurogenesis and myelinization could be novel therapeutic targets against Alzheimer's disease (AD). Intracerebroventricular (icv) injection of streptozotocin (STZ) induces neurodegeneration through multiple mechanisms ultimately resulting in reduced adult neurogenesis. Previously, the multitarget compound QTC-4-MeOBnE (1-(7-chloroquinolin-4-yl)-N-(4-methoxybenzyl)-5-methyl-1H-1,2,3-triazole-4-carboxamide) demonstrated beneficial effects in preclinical models of AD. Here we investigated its pharmacokinetics profile and the effect on memory impairments and neurodegeneration induced by STZ. Two icv injections of STZ resulted in significant cognitive and memory impairments, assessed by novel object recognition, Y-maze, social recognition, and step-down passive avoidance paradigms. These deficits were reversed in STZ-injected mice treated with QTC-4-MeOBnE. This effect was associated with reversion of neuronal loss in hippocampal dentate gyrus, reduced oxidative stress, and amelioration of synaptic function trough Na+/K+ ATPase and acetylcholinesterase activities. Furthermore, brains from QTC-4-MeOBnE-treated mice had a significant increase in adult neurogenesis and remyelination through Prox1/NeuroD1 and Wnt/ß-catenin pathways. Overall, our findings support the potential anti-AD effect of QTC-4-MeOBnE through multiple pathways, all of which have been involved in the onset and progression of the disease.
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Enfermedad de Alzheimer , Enfermedad de Alzheimer/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Aprendizaje por Laberinto , Trastornos de la Memoria/tratamiento farmacológico , Ratones , Neurogénesis , Estrés Oxidativo , Estreptozocina/toxicidadRESUMEN
We investigated the adverse effects of the anabolic androgenic steroids (AAS) boldenone (BOL) and stanazolol (ST) on the enzymatic antioxidant systems of the rat liver. Male Wistar rats were divided in three protocols (P): PI, 5 mg/kg BOL or ST once a week for 4 weeks; PII, 2.5 mg/kg BOL or ST once a week for 8 weeks; PIII, 1.25 mg/kg BOL or ST once a week for 12 weeks. AAS were administered intramuscularly (0.2 ml, olive oil vehicle) once a week in all protocols. Activities of the enzymes glutathione peroxidase (GPx), glutathione S-transferase (GST), and glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), were investigated. We assessed the content of hydrogen peroxide (H2O2), glycogen and lactate; and enzyme markers of neutrophils (myeloperoxidase, MPO) and macrophages (NAGase). PI and PII altered the SOD and CAT activities and increased the H2O2 content. PI led to increases in the MPO and NAGase activities. In contrast, changes in GPx, GST and, GR were observed under PII and, to a greater extend, under PIII. Following PIII, GPx, GR, and GST exhibited reduced activities. All protocols altered the glycogen and lactate content. The use of high doses of AAS for a short duration first alters SOD/CAT activity. In contrast, at lower doses of AAS for long periods is associated with changes in the glutathione system. Protocols with high doses of AAS for a short duration exert the most deleterious effects on redox status, markers of cellular infiltration, and the metabolic functioning of hepatic tissues.
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Antioxidantes/metabolismo , Glucógeno/metabolismo , Ácido Láctico/metabolismo , Hígado/efectos de los fármacos , Hígado/enzimología , Estanozolol/farmacología , Testosterona/análogos & derivados , Acetilglucosaminidasa/metabolismo , Animales , Relación Dosis-Respuesta a Droga , Hígado/metabolismo , Peroxidasa/metabolismo , Ratas , Ratas Wistar , Testosterona/farmacología , Factores de TiempoRESUMEN
The ubiquitous presence of aluminum in the environment leads to a high likelihood of human exposure. Neurotoxicity of the trivalent cationic form of this metal (Al3+) occurs in the central nervous system via accumulation of Al in cells of neural origin, including neural progenitor cells (NPCs). NPCs play a key role in the development and regeneration of the brain throughout life; therefore, this metal may contribute to neuropathological conditions. Here, we evaluated the effects of different Al3+ concentrations (0-50⯵M) on the purinergic system of NPCs isolated from embryonic telencephalons, cultured as neurospheres. Al3+ adhered to the cell surface of neurospheres reducing extracellular ATP release, as well as ATP, ADP, and AMP hydrolysis by NTPDase and 5'-nucleotidase, respectively. In addition, impaired nucleotide release by Al3+ reduced P2Y1 and adenosine A2A receptors expression in differentiated neurospheres. These receptors are crucial for NPC proliferation during brain development and self-repair against external stimuli, such as metal exposure. Thus, Al3+ represents an environmental agent linked to neurodegeneration through alterations in the ATP-signalling pathway, proving to be a potential mechanism associated with NPC proliferation and brain degeneration.
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Aluminio/toxicidad , 5'-Nucleotidasa , Adenosina Trifosfato/metabolismo , Aluminio/metabolismo , Animales , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Sistema Nervioso Central/metabolismo , Proteínas Ligadas a GPI , Humanos , Transducción de Señal/efectos de los fármacos , Células Madre , Pruebas de ToxicidadRESUMEN
RATIONALE: Inosine is a naturally occurring purine nucleoside formed by adenosine breakdown. This nucleoside is reported to exert potent effects on memory and learning, possibly through its antioxidant and anti-inflammatory actions. OBJECTIVE: The objective is to evaluate the effects of inosine on the behavioral and neurochemical parameters in a rat model of Alzheimer's disease (AD) induced by streptozotocin (STZ). METHODS: Adult male rats were divided into four groups: control (saline), STZ, STZ plus inosine (50 mg/kg), and STZ plus inosine (100 mg/kg). STZ (3 mg/kg) was administered by bilateral intracerebroventricular injection. The animals were treated intraperitoneally with inosine for 25 days. Memory, oxidative stress, ion pump activities, acetylcholinesterase (AChE), and choline acetyltransferase (ChAT) activities and expression were evaluated in the cerebral cortex and hippocampus. RESULTS: The memory impairment induced by STZ was prevented by inosine. An increase in the Na+, K+-ATPase, and Mg-ATPase activities and a decrease in the Ca2+-ATPase activity were induced by STZ in the hippocampus and cerebral cortex, and inosine could prevent these alterations in ion pump activities. Inosine also prevented the increase in AChE activity and the alterations in AChE and ChAT expression induced by STZ. STZ increased the reactive oxygen species, nitrite levels, and superoxide dismutase activity and decreased the catalase and glutathione peroxidase activities. Inosine treatment conferred protection from these oxidative alterations in the brain. CONCLUSIONS: Our findings demonstrate that inosine affects brain multiple targets suggesting that this molecule may have therapeutic potential against cognitive deficit and tissue damage in AD.
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Enfermedad de Alzheimer/tratamiento farmacológico , Modelos Animales de Enfermedad , Sistemas de Liberación de Medicamentos/métodos , Inosina/administración & dosificación , Trastornos de la Memoria/prevención & control , Fármacos Neuroprotectores/administración & dosificación , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/metabolismo , Animales , Antioxidantes/administración & dosificación , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Relación Dosis-Respuesta a Droga , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/fisiología , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Estreptozocina/toxicidadRESUMEN
Aluminum (Al) is a neurotoxin and is associated with the etiology of neurodegenerative diseases, such as Alzheimer's disease (AD). The Al-free ion (Al3+) is the biologically reactive and toxic form. However, the underlying mechanisms of Al toxicity in the brain remain unclear. Here, we evaluated the effects of Al3+ (in the chloride form-AlCl3) at different concentrations (0.1-100 µM) on the morphology, proliferation, apoptosis, migration and differentiation of neural progenitor cells (NPCs) isolated from embryonic telencephalons, cultured as neurospheres. Our results reveal that Al3+ at 100 µM reduced the number and diameter of neurospheres. Cell cycle analysis showed that Al3+ had a decisive function in proliferation inhibition of NPCs during neural differentiation and induced apoptosis on neurospheres. In addition, 1 µM Al3+ resulted in deleterious effects on neural phenotype determination. Flow cytometry and immunocytochemistry analysis showed that Al3+ promoted a decrease in immature neuronal marker ß3-tubulin expression and an increase in co-expression of the NPC marker nestin and glial fibrillary acidic protein. Thus, our findings indicate that Al3+ caused cellular damage and reduced proliferation and migration, resulting in global inhibition of NPC differentiation and neurogenesis.
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Cloruro de Aluminio/toxicidad , Células Madre Embrionarias/efectos de los fármacos , Células-Madre Neurales/efectos de los fármacos , Neurogénesis/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Células Cultivadas , Relación Dosis-Respuesta a Droga , Células Madre Embrionarias/patología , Femenino , Masculino , Ratones , Células-Madre Neurales/patología , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/fisiopatología , Fenotipo , Telencéfalo/efectos de los fármacos , Telencéfalo/embriologíaRESUMEN
Cigarette smoking is directly associated with lung cancer. Non-small cell lung carcinoma (NSCLC) represents approximately 80% from all types of lung cancer. This latter is hard to diagnose and to treat due to the lack of symptoms in early stages of the disease. The aim of this study was to evaluate ADA activity and the expression of P2X7, A1, and A2A receptors and in lymphocytes. In addition, the profile of pro-inflammatory and anti-inflammatory cytokines serum levels of patients with lung cancer in advanced stage was evaluated. Patients (n = 13) previously treated for lung cancer at stage IV (UICC) with chemotherapy had their blood collected. Cancer patients showed a decrease in ADA activity and an increase in A1 receptor expression in lymphocytes when compared to the control group. Moreover, patients exhibited an increase in IL-6 and TNF-α, while IL-17 and INF-Ï serum levels were lower in patients with lung cancer. The decreased ADA activity and the increase in A1 receptor expression may contribute to adenosine pro-tumor effects by increasing IL-6 and TNF-α and decreasing IL-17 and INF-γ serum levels. Our data show an indirect evidence that purinergic signaling may have a role in promoting a profile of cytokines levels that favors tumor progression.
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Adenosina Desaminasa/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/enzimología , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/patología , Linfocitos/enzimología , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Citocinas/sangre , Femenino , Humanos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/metabolismo , Linfocitos/metabolismo , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Receptores Purinérgicos/metabolismo , Transducción de SeñalRESUMEN
ABSTRACT Nicotine delays the healing process and increases the levels of myeloperoxidase (MPO), an enzyme that plays a key role in the production of reactive oxygen species during the inflammatory process. Laser Photobiomodulation (PBM) is one of the most used electrophysical agents in the treatment of the calcaneal tendon, however, its effects on MPO activity need to be further elucidated. This study aimed to evaluate the effects of laser PBM on MPO activity after inflicting an injury to the calcaneal tendon of rats exposed to cigarette smoke. Thirty-four male Wistar rats with 90 days of age were used. After 14 days of exposure to cigarette smoke, the animals were divided into three experimental groups: control group (CG, n=12), not submitted to injury or treatment; sham group (ShG, n=10), submitted to partial calcaneal tendon injury and laser PBM simulation; and laser PBM group (PBMG, n=12), submitted to partial calcaneal tendon lesion and treated with laser PBM within the first minute after injury. PBM decreased MPO activity levels in PBMG compared to ShG (CG: 1.38±0.69pg/ml; ShG: 3.78±1.09pg/ml; PBMG: 2.58±0.93pg/ml; p<0.005). In conclusion, applying laser PBM immediately after inflicting damage to the calcaneal tendon attenuates acute inflammatory activity in rats exposed to cigarette smoke.
RESUMO A nicotina retarda o processo de cicatrização e eleva os níveis da enzima mieloperoxidase (MPO), a qual possui um papel fundamental na produção de espécies reativas de oxigênio durante o processo inflamatório. A fotobiomodulação laser (FBM) é um dos agentes eletrofísicos mais utilizados no tratamento do tendão calcâneo, no entanto, os seus efeitos sobre a atividade da MPO carecem de maior elucidação. Este estudo objetivou avaliar os efeitos da FBM sobre a atividade da MPO, após lesão do tendão calcâneo em ratos expostos à fumaça de cigarro. Foram utilizados 34 ratos Wistar, machos, com 90 dias de vida. Após 14 dias de exposição à fumaça de cigarro, os animais foram divididos em três grupos experimentais: grupo controle (GC, n=12), não submetido à lesão ou tratamento; grupo sham (GSh, n=10), submetido à lesão parcial do tendão calcâneo e a simulação da FBM laser; grupo FBM laser (GFBM, n=12), submetido à lesão parcial do tendão calcâneo e tratados com FBM laser, no primeiro minuto após a lesão. A FBM diminuiu os níveis de atividade da MPO no GFBM em comparação ao GSh (GC: 1,38±0,69 pg/ml; GSh: 3,78±1,09pg/ml; GFBM: 2,58±0,93pg/ml; p<0,005). Conclui-se que a FBM laser aplicada imediatamente após lesão do tendão calcâneo, atenua a atividade inflamatória aguda em ratos expostos à fumaça de cigarro.
RESUMEN La nicotina retarda el proceso de cicatrización y eleva los niveles de la enzima mieloperoxidasa (MPO), que tiene un papel fundamental en la producción de especies reactivas de oxígeno durante el proceso inflamatorio. La fotobiomodulación con láser (FBM) es uno de los agentes electrofísicos más utilizados en el tratamiento del tendón calcáneo, sin embargo sus efectos sobre la actividad de la MPO carecen de mayor elucidación. Este estudio objetivó evaluar los efectos de la FBM sobre la actividad de la MPO después de lesión del tendón calcáneo en ratones expuestos al humo de cigarrillo. Se utilizaron 34 ratones Wistar, machos, con 90 días de vida. Después de 14 días de exposición al humo de cigarrillo, los animales fueron divididos en tres grupos experimentales: grupo de control (GC, n=12), no sometido a la lesión o tratamiento; grupo sham (GSh, n=10), sometido a la lesión parcial del tendón calcáneo y a la simulación de la FBM láser; y el grupo FBM láser (GFBM, n=12), sometido a la lesión parcial del tendón calcáneo y tratado con FBM láser, en el primer minuto después de la lesión. La FBM disminuyó los niveles de actividad de MPO en el GFBM en comparación con el GSh (GC: 1,38±0,69 pg/ml; GSh: 3,78±1,09pg/ml; GFBM: 2,58±0,93pg/ml, p<0,005). Se concluye que la FBM láser aplicada inmediatamente después de la lesión del tendón calcáneo atenúa la actividad inflamatoria aguda en ratones expuestos al humo de cigarrillo.
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Animales , Tendón Calcáneo/fisiopatología , Contaminación por Humo de Tabaco/efectos adversos , Terapia por Luz de Baja Intensidad , Tendinopatía/terapia , Cicatrización de Heridas/fisiología , Ratas Wistar , Modelos Animales , Inflamación/fisiopatología , Nicotina/efectos adversosRESUMEN
OBJECTIVE: Investigate Vitamin D3 (VD3) effect on the Acetylcholinesterase (AChE), oxidative damage and behavioral tests in animals subjected to Intracerebroventicular injection of Streptozotocin (ICV-STZ) simulating a Sporadic Dementia of Alzheimer's Type (SDAT) and treated with VD3 (21 days). METHODS: Animals were divided into eight groups: Vehicle, VD12.5â µg/kg, VD42â µg/kg, VD125â µg/kg, STZ, STZ+VD12.5â µg/kg, STZ+VD42â µg/kg, STZ+VD125â µg/kg. RESULTS: VD3 prevented the increase in AChE in groups of VD42â µg/kg and VD125â µg/kg; in AChE of synaptossomes and TBARS levels prevented the increase in group VD125â µg/kg; in ROS levels there was not a significant difference; for the Carbonyl Content all doses prevented the increase. Total Thiols prevent the decrease in VD42â µg/kg and VD125â µg/kg, and Reduced Glutathione prevented the decrease in VD125â µg/kg, Oxidized Glutathione prevented the increase in VD125â µg/kg. In relation to behavioral tests, the VD3 prevented the increase in time to find (days 2 and 3), in the time to find the platform (day 3) and in time spent in the quadrant (day 2). However, in relation to crossings there was not difference in groups. These results indicated the therapeutic effect of the VD3 in model of STZ in rats.
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Acetilcolinesterasa/metabolismo , Enfermedad de Alzheimer/metabolismo , Antioxidantes/metabolismo , Colecalciferol/uso terapéutico , Animales , Ácido Ascórbico/metabolismo , Demencia/metabolismo , Modelos Animales de Enfermedad , Peroxidación de Lípido/efectos de los fármacos , Masculino , Memoria/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismoRESUMEN
The aim of this study was to investigate the effects of scalp acupuncture and electrostimulation, combined or not, in a disuse model consisted of early sensorimotor restriction in rats. Male Wistar pups received sensorimotor restriction from the second postnatal day (P2) until P28. Animals were divided into five different groups (n = 6): control (CT), sensorimotor restricted (SR), acupuncture (AC), electrostimulation (EL), and electroacupuncture (AC+EL). Experimental animals received sham, acupuncture, or electrical stimulation, combined or not, of two scalp regions for 7 days (P29-P35). Before treatment period (P29) and after treatment (P36), animals were evaluated with the narrow suspended bar, horizontal ladder, and stride length tests. SR animals had worse performance in the narrow suspended and horizontal ladder tasks compared with SR animals at P29 (p ≤ 0.005). Significant improvements were observed in both tasks in AC, EL, and EL+AC groups comparing P29 and P36 (p < 0.001). Also, at P35, all treated animals performed significantly better motor tasks compared with SR group (p < 0.05). There was no difference between treated groups. Finally, acupuncture and electrical stimulation, combined or not, have beneficial effect on motor performance following early developmental disuse.
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Terapia por Acupuntura/métodos , Enfermedades del Sistema Nervioso/terapia , Animales , Conducta Animal/fisiología , Masculino , Ratas , Ratas Wistar , Cuero Cabelludo/fisiologíaRESUMEN
: Background: Central nervous system function has been emerging as an approach to understand hypertension-mediated memory dysfunction, and chronic exercise is able to modulate the purinergic system. METHOD: Herein, we investigated the effect of chronic swimming training on the purinergic system in cortex and hippocampus of L-NAME-induced hypertensive rats. Male Wistar rats were divided into four groups: Control, Exercise, L-NAME and Exercise L-NAME. Inhibitory avoidance test was used to assess memory status. NTPDase, CD73 and adenosine deaminase activities and expression, and P2 receptors expression were analyzed. Data were analyzed using two-way ANOVA and Kruskal-Wallis tests, considering P less than 0.05. RESULTS: Physical exercise reduced the blood pressure and prevented memory impairment induced by L-NAME model of hypertension. L-NAME treatment promoted an increase in NTPDase1, NTPDase3 and CD73 expression and activity in the cortex. A2A expression is increased in hippocampus and cortex in the hypertension group and exercise prevented this overexpression. CONCLUSION: These changes suggest that hypertension increases adenosine generation, which acts through A2A receptors, and exercise prevents these effects. These data may indicate a possible mechanism by which exercise may prevent memory impairment induced by L-NAME.
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5'-Nucleotidasa/metabolismo , Antígenos CD/metabolismo , Apirasa/metabolismo , Hipertensión/fisiopatología , Memoria/fisiología , Condicionamiento Físico Animal/fisiología , Animales , Corteza Cerebral/química , Corteza Cerebral/metabolismo , Modelos Animales de Enfermedad , NG-Nitroarginina Metil Éster/metabolismo , Ratas , Receptor de Adenosina A2A/metabolismo , Natación/fisiologíaRESUMEN
This study investigated the antioxidant activity of Cuphea glutinosa (CG) and its effect on Na+, K+-ATPase from cardiac muscle. The ethanolic extract showed higher antioxidant capacity compared to aqueous and ethyl acetate fraction. Ethyl acetate fraction showed ß-sitosterol-3-O-ß-glucoside, kaempferol, quercetin, isoquercetin, gallic acid methyl ester, and gallic acid. The ethanolic extract also reduced the Na+,K+-ATPase activity. CG presented a promising antioxidant activity and inhibitory effect on the Na+, K+-ATPase activity, supporting biochemical evidences the popular use of this plant in the treatment of heart failure.
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Antioxidantes/aislamiento & purificación , Cuphea/química , Fitoquímicos/química , ATPasa Intercambiadora de Sodio-Potasio/antagonistas & inhibidores , Animales , Antioxidantes/química , Brasil , Corazón/efectos de los fármacos , Insuficiencia Cardíaca/tratamiento farmacológico , Quempferoles/aislamiento & purificación , Miocardio , Extractos Vegetales/química , Quercetina/aislamiento & purificaciónRESUMEN
This study evaluated the effects of caffeine in combination with high-intensity interval training (HIIT) on sensitivity to glucocorticoids and proliferation of lymphocytes, IL-6 and IL-10 levels and NTPDase, adenosine deaminase (ADA) and acetylcholinesterase (AChE) activity in rat lymphocytes. The animals were divided into groups: control, caffeine 4 mg/kg, caffeine 8 mg/kg, HIIT, HIIT plus caffeine 4 mg/kg and HIIT plus caffeine 8 mg/kg. The rats were trained three times a week for 6 weeks for a total workload 23% of body weight at the end of the experiment. Caffeine was administered orally 30 min before the training session. When lymphocytes were stimulated with phytohaemagglutinin no changes were observed in proliferative response between trained and sedentary animals; however, when caffeine was associated with HIIT an increase in T lymphocyte proliferation and in the sensitivity of lymphocytes to glucocorticoids occurred. ATP and ADP hydrolysis was decreased in the lymphocytes of the animals only trained and caffeine treatment prevented alterations in ATP hydrolysis. HIIT caused an increase in the ADA and AChE activity in lymphocytes and this effect was more pronounced in rats trained and supplemented with caffeine. The level of IL-6 was increased while the level of IL-10 was decreased in trained animals (HIIT) and caffeine was capable of preventing this exercise effect. Our findings suggest that caffeine ingestion attenuates, as least in part, the immune and inflammatory alterations following a prolonged HIIT protocol.