RESUMEN
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.
Asunto(s)
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
Hypermethioninemia is a disorder characterized by high plasma levels of methionine (Met) and its metabolites such as methionine sulfoxide (MetO). Studies have reported associated inflammatory complications, but the mechanisms involved in the pathophysiology of hypermethioninemia are still uncertain. The present study aims to evaluate the effect of chronic administration of Met and/or MetO on phenotypic characteristics of macrophages, in addition to oxidative stress, purinergic system, and inflammatory mediators in macrophages. In this study, Swiss male mice were subcutaneously injected with Met and MetO at concentrations of 0.35-1.2 g/kg body weight and 0.09-0.3 g/kg body weight, respectively, from the 10th-38th day post-birth, while the control group was treated with saline solution. The results revealed that Met and/or MetO induce an M1/classical activation phenotype associated with increased levels of tumor necrosis factor alpha and nitrite, and reduced arginase activity. It was also found that Met and/or MetO alter the activity of antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, as well as the levels of thiol and reactive oxygen species in macrophages. The chronic administration of Met and/or MetO also promotes alteration in the hydrolysis of ATP and ADP, as indicated by the increased activity of ectonucleotidases. These results demonstrate that chronic administration of Met and/or MetO promotes activated pro-inflammatory profile by inducing M1/classical macrophage polarization. Thus, the changes in redox status and purinergic system upon chronic Met and/or MetO exposure may contribute towards better understanding of the alterations consistent with hypermethioninemic patients.
Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/inmunología , Glicina N-Metiltransferasa/deficiencia , Macrófagos/inmunología , Metionina/análogos & derivados , Animales , Catalasa/metabolismo , Polaridad Celular , Glutatión Peroxidasa/metabolismo , Glicina N-Metiltransferasa/inmunología , Macrófagos/efectos de los fármacos , Masculino , Metionina/administración & dosificación , Metionina/metabolismo , Metionina/farmacología , Ratones , Oxidación-Reducción , Estrés Oxidativo , Fenotipo , Superóxido Dismutasa/metabolismoRESUMEN
Tannic acid (TA) is a hydrolysable glycosidic polyphenol polymer of gallic acid, which possesses neuroprotective properties. The aim of this study was to evaluate the effect of TA treatment on cognitive performance and neurochemical changes in an experimental model of sporadic dementia of Alzheimer's type (SDAT) induced by intracerebroventricular (ICV) injection of streptozotocin (STZ) and to explore the potential cellular and molecular mechanisms underlying these effects. Adult male rats were divided into four groups: control, TA, STZ, and TA + STZ. Animals from TA and TA + STZ groups were treated with TA (30 mg/kg) daily, by gavage, for 21 days; others groups received water (1 mL/kg). Subsequently, an ICV injection of STZ (3 mg/kg) was administered into the lateral ventricles of animals from STZ and TA + STZ groups, while other groups received citrate buffer. Cognitive deficits (short-term memory), neuronal survival, neuroinflammation as well as expression of SNAP-25, Akt, and pAkt were evaluated in the cerebral cortex. TA treatment protected against the impairment of memory in STZ-induced SDAT. STZ promoted an increase in neuronal death and the levels of proinflammatory cytokines (IL-6 and TNF-α) and a decrease in Akt and pAkt expression; TA was able to restore these changes. Neither STZ nor TA altered SNAP-25 expression or the levels of IL-12 and IL-4 in the cerebral cortex. Our study highlights that treatment with TA prevents memory deficits and reestablishes Akt and pAkt expression, protecting against neuronal death and neuroinflammation in STZ-induced SDAT in rats.
Asunto(s)
Enfermedad de Alzheimer/metabolismo , Mediadores de Inflamación/metabolismo , Trastornos de la Memoria/metabolismo , Proteínas Proto-Oncogénicas c-akt/biosíntesis , Estreptozocina/toxicidad , Taninos/uso terapéutico , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/prevención & control , Animales , Reacción de Prevención/efectos de los fármacos , Reacción de Prevención/fisiología , Muerte Celular/efectos de los fármacos , Muerte Celular/fisiología , Mediadores de Inflamación/antagonistas & inhibidores , Masculino , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/prevención & control , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Ratas , Ratas Wistar , Taninos/farmacologíaRESUMEN
Bipolar disorder is a chronic mood disorder characterized by episodes of mania and depression. The aim of this study was to investigate the effects of blackberry extract on behavioral parameters, oxidative stress and inflammatory markers in a ketamine-induced model of mania. Animals were pretreated with extract (200â¯mg/kg, once a day for 14 days), lithium chloride (45â¯mg/kg, twice a day for 14 days), or vehicle. Between the 8th and 14th days, the animals received an injection of ketamine (25â¯mg/kg) or vehicle. On the 15th day, thirty minutes after ketamine administration, the animals' locomotion was assessed using open-field apparatus. After the experiments, the animals were euthanized and cerebral structures were removed for neurochemical analyses. The results showed that ketamine treatment induced hyperlocomotion and oxidative damage in the cerebral cortex, hippocampus and striatum. In contrast, pretreatment with the extract or lithium was able to prevent hyperlocomotion and oxidative damage in the cerebral cortex, hippocampus, and striatum. In addition, IL-6 and IL-10 levels were increased by ketamine, while the extract prevented these effects in the cerebral cortex. Pretreatment with the extract was also effective in decreasing IL-6 and increasing the level of IL-10 in the striatum. In summary, our findings suggest that blackberry consumption could help prevent or reduce manic episodes, since this extract have demonstrated neuroprotective properties as well as antioxidant and anti-inflammatory effects in the ketamine-induced mania model.
Asunto(s)
Antocianinas , Frutas , Manía/metabolismo , Extractos Vegetales/farmacología , Rubus , Animales , Antimaníacos/farmacología , Conducta Animal/efectos de los fármacos , Catalasa/efectos de los fármacos , Catalasa/metabolismo , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Citocinas/efectos de los fármacos , Citocinas/metabolismo , Modelos Animales de Enfermedad , Antagonistas de Aminoácidos Excitadores/toxicidad , Glutatión Peroxidasa/efectos de los fármacos , Glutatión Peroxidasa/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Ketamina/toxicidad , Cloruro de Litio/farmacología , Manía/inducido químicamente , Manía/fisiopatología , Neostriado/efectos de los fármacos , Neostriado/metabolismo , Prueba de Campo Abierto , Extractos Vegetales/química , Ratas , Superóxido Dismutasa/efectos de los fármacos , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
Abstract Intense physical activity can increase oxidative stress and muscle damage in, causing fatigue and injury. Graduated compression stockings (GCS) can decrease these deleterious effects. The aim was to determine the acute effects of GCS on muscle damage and oxidative stress (OS) in garbage collectors. Thirteen garbage collectors, 25.4±5.2 years, participated using GCS or placebo stockings. Blood samples were collected at pre and post a working day and after 16 hours of rest. Markers of OS and muscle damage were evaluated. Two-way ANOVA (two conditions and two moments) was used for the analysis of the outcomes No significant differences were found for creatine kinase, catalase and glutathione peroxidase between the time and groups. There was a significant difference for the total thiol content and superoxide dismutase only in the control group (pre and post, p = 0.004). The use of GCS exerted acute protection against the increase of markers of OS, but did not contribute to attenuate muscle damage.
Resumo Atividade física intensa pode aumentar o estresse oxidativo e danos musculares, causando fadiga e lesões. As meias de compressão graduada (MCG) podem diminuir esses efeitos deletérios. O objetivo foi determinar os efeitos agudos da MCG no dano muscular e estresse oxidativo (EO) em coletores de lixo. Treze coletores de lixo, 25,4 ± 5,2 anos, participaram usando MCG ou placebo. As amostras de sangue foram coletadas antes e após um dia útil e após 16 horas de descanso. Marcadores de EO e dano muscular foram avaliados. ANOVA de duas vias (duas condições e dois momentos) foi usada para á análise dos resultados. Não foram encontradas diferenças significativas para creatina quinase, catalase e glutationa peroxidase entre o tempo e os grupos. Houve uma diferença significativa para o conteúdo total tiólico e superóxido dismutase apenas no grupo controle (pré e pós, p = 0,004). O uso de MCG exerceu proteção aguda contra o aumento de marcadores de EO, mas não contribuiu para atenuar danos musculares
RESUMEN
Among gliomas types, glioblastoma is considered the most malignant and the worst form of primary brain tumor. It is characterized by high infiltration rate and great angiogenic capacity. The presence of an inflammatory microenvironment contributes to chemo/radioresistance, resulting in poor prognosis for patients. Recent data show that thiazolidinones have a wide range of pharmacological properties, including anti-inflammatory and antiglioma activities. Nanocapsules of biodegradable polymers become an alternative to cancer treatment since they provide targeted drug delivery and could overcome blood-brain barrier. Therefore, here we investigated the in vitro antiglioma activity and the potential in vivo toxicity of 2- (2-methoxyphenyl) -3- ((piperidin-1-yl) ethyl) thiazolidin-4-one-loaded polymeric nanocapsules (4L-N). Nanocapsules were prepared and characterized in terms of particle size, polydispersity index, zeta potential, pH, molecule content and encapsulation efficiency. Treatment with 4L-N selectively decreased human U138MG and rat C6 cell lines viability and proliferation, being even more efficient than the free-form molecule (4L). In addition, 4L-N did not promote toxicity to primary astrocytes. We further demonstrated that the treatment with sub-therapeutic dose of 4L-N did not alter weight, neither resulted in mortality, toxicity or peripheral damage to Wistar rats. Finally, 4L as well as 4L-N did not alter makers of oxidative damage, such as TBARS levels and total sulfhydryl content, and did not change antioxidant enzymes SOD and CAT activity in liver and brain of treated rats. Taken together, these data indicate that the nanoencapsulation of 4L has potentiated its antiglioma effect and does not cause in vivo toxicity.
Asunto(s)
Neoplasias Encefálicas/tratamiento farmacológico , Glioma/tratamiento farmacológico , Nanocápsulas/química , Piperidinas/toxicidad , Piperidinas/uso terapéutico , Polímeros/química , Tiazolidinas/toxicidad , Tiazolidinas/uso terapéutico , Animales , Apoptosis/efectos de los fármacos , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Astrocitos/patología , Biomarcadores de Tumor/sangre , Encéfalo/efectos de los fármacos , Encéfalo/patología , Neoplasias Encefálicas/sangre , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Liberación de Fármacos , Glioma/sangre , Glioma/patología , Humanos , Luz , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Estrés Oxidativo/efectos de los fármacos , Piperidinas/síntesis química , Piperidinas/química , Polímeros/síntesis química , Ratas Wistar , Tiazolidinas/síntesis química , Tiazolidinas/química , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Pruebas de Toxicidad , Pérdida de Peso/efectos de los fármacosRESUMEN
BACKGROUND: Glioblastomas are the most devastating brain tumor characterized by chemoresistance development and poor prognosis. Macrophages are a component of tumor microenvironment related to glioma malignancy. The relation among inflammation, innate immunity and cancer is accepted; however, molecular and cellular mechanisms mediating this relation and chemoresistance remain unresolved. OBJECTIVE: Here we evaluated whether glioma sensitive or resistant to temozolomide (TMZ) modulate macrophage polarization and inflammatory pathways associated. The impact of glioma-macrophage crosstalk on glioma proliferation was also investigated. METHODS: GL261 glioma chemoresistance was developed by exposing cells to increasing TMZ concentrations over a period of 6months. Mouse peritoneal macrophages were exposed to glioma-conditioned medium or co-cultured directly with glioma sensitive (GL) or chemoresistant (GLTMZ). Macrophage polarization, in vitro and in vivo glioma proliferation, redox parameters, ectonucleotidase activity and ATP cytotoxicity were performed. RESULTS: GLTMZ cells were more effective than GL in induce M2-like macrophage polarization and in promote a strong immunosuppressive environment characterized by high IL-10 release and increased antioxidant potential, which may contribute to glioma chemoresistance and proliferation. Interestingly, macrophage-GLTMZ crosstalk enhanced in vitro and in vivo proliferation of chemoresistant cells, decreased ectonucleotidase activities, which was followed by increased macrophage sensitivity to ATP induced death. CONCLUSIONS: Results suggest a differential macrophage modulation by GLTMZ cells, which may favor the maintenance of immunosuppressive tumor microenvironment and glioma proliferation. GENERAL SIGNIFICANCE: The induction of immunosuppressive environment and macrophage education by chemoresistant gliomas may be important for tumor recovery after chemotherapy and could be considered to overcome chemoresistance development.
Asunto(s)
Dacarbazina/análogos & derivados , Resistencia a Antineoplásicos/genética , Glioma/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Animales , Antineoplásicos Alquilantes/administración & dosificación , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Polaridad Celular/efectos de los fármacos , Dacarbazina/administración & dosificación , Modelos Animales de Enfermedad , Glioma/metabolismo , Glioma/patología , Humanos , Inflamación/metabolismo , Inflamación/patología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Receptores Purinérgicos/genética , Temozolomida , Microambiente Tumoral/efectos de los fármacosRESUMEN
Glioblastoma multiforme (GBM) is the worst form of primary brain tumor, which has a high rate of infiltration and resistance to radiation and chemotherapy, resulting in poor prognosis for patients. Recent studies show that thiazolidinones have a wide range of pharmacological properties including antimicrobial, anti-inflammatory, anti-oxidant and anti-tumor. Here, we investigate the effect antiglioma in vitro of a panel of sixteen synthetic 2-aryl-3-((piperidin-1-yl)ethyl)thiazolidin-4-ones where 13 of these decreased the viability of glioma cells 30-65% (100 µM) compared with controls. The most promising compounds such as 4d, 4l, 4m and 4p promoted glioma reduction of viability greater than 50%, were further tested at lower concentrations (12.5, 25, 50 and 100 µM). Also, the data showed that the compounds 4d, 4l, 4m and 4p induced cell death primarily through necrosis and late apoptosis mechanisms. Interestingly, none of these 2-aryl-3-((piperidin-1-yl)ethyl)thiazolidin-4-ones were cytotoxic for primary astrocytes, which were used as a non-transformed cell model, indicating selectivity. Our results also show that the treatment with sub-therapeutic doses of 2-aryl-3-((piperidin-1-yl)ethyl)thiazolidin-4-ones (4d, 4l and 4p) reduced in vivo glioma growth as well as malignant characteristics of implanted tumors such as intratumoral hemorrhage and peripheral pseudopalisading. Importantly, 2-aryl-3-((piperidin-1-yl)ethyl)thiazolidin-4-ones treatment did not induce mortality or peripheral damage to animals. Finally, 2-aryl-3-((piperidin-1-yl)ethyl)thiazolidin-4-ones also changed the nitric oxide metabolism which may be associated with reduced growth and malignity characteristics of gliomas. These data indicates for the first time the therapeutic potential of synthetic 2-aryl-3-((piperidin-1-yl)ethyl)thiazolidin-4-ones to GBM treatment.
Asunto(s)
Antineoplásicos/farmacología , Neoplasias Encefálicas/patología , Proliferación Celular/efectos de los fármacos , Glioblastoma/patología , Modelos Biológicos , Tiazolidinas/farmacología , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Ratas , Ratas WistarRESUMEN
Methionine is an essential amino acid involved in critical metabolic process, and regulation of methionine flux through metabolism is important to supply this amino acid for cell needs. Elevation in plasma methionine commonly occurs due to mutations in methionine-metabolizing enzymes, such as methionine adenosyltransferase. Hypermethioninemic patients exhibit clinical manifestations, including neuronal and liver disorders involving inflammation and tissue injury, which pathophysiology is not completely established. Here, we hypothesize that alterations in macrophage inflammatory response may contribute to deleterious effects of hypermethioninemia. To this end, macrophage primary cultures were exposed to methionine (1 mM) and/or its metabolite methionine sulfoxide (0.5 mM), and M1/proinflammatory or M2/anti-inflammatory macrophage polarization was evaluated. In addition, inflammation-related pathways including oxidative stress parameters, as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities; reactive oxygen species (ROS) production, and purinergic signaling, as ATP/ADP/AMPase activities, were investigated. Methionine and/or methionine sulfoxide induced M1/classical macrophage activation, which is related to proinflammatory responses characterized by increased iNOS activity and TNF-α release. Further experiments showed that treatments promoted alterations on redox state of macrophages by differentially modulated SOD and CAT activities and ROS levels. Finally, methionine and/or methionine sulfoxide treatment also altered the extracellular nucleotide metabolism, promoting an increase of ATPase/ADPase activities in macrophages. In conclusion, these findings contribute to better understand the participation of proinflammatory responses in cell injury observed in hypermethioninemic patients.
Asunto(s)
Macrófagos/metabolismo , Metionina/análogos & derivados , Metionina/farmacología , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Animales , Catalasa/metabolismo , Glutatión Peroxidasa/metabolismo , Masculino , Ratones , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
Cecropia species are widely used in traditional medicine by its anti-diabetic, anti-hypertensive and anti-inflammatory properties. In the present study, we investigated the neuroprotective and antioxidant effects of the crude aqueous extract from Cecropia pachystachya leaves in a rat model of mania induced by ketamine. The results indicated that ketamine treatment (25 mg/kg i.p., for 8 days) induced hyperlocomotion in the open-field test and oxidative damage in prefrontal cortex and hippocampus, evaluated by increased lipid peroxidation, carbonyl protein formation and decreased total thiol content. Moreover, ketamine treatment reduced the activity of the antioxidant enzymes superoxide dismutase and catalase in hippocampus. Pretreatment of rats with C. pachystachya aqueous extract (200 and 400 mg/kg p.o., for 14 days) or with lithium chloride (45 mg/kg p.o., for 14 days, used as a positive control) prevented both behavioral and pro-oxidant effects of ketamine. These findings suggest that C. pachystachya might be a useful tool for preventive intervention in bipolar disorder, reducing the episode relapse and the oxidative damage associated with the manic phase of this disorder .
Asunto(s)
Trastorno Bipolar/prevención & control , Ketamina/toxicidad , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Urticaceae/química , Animales , Conducta Animal , Cromatografía Líquida de Alta Presión , Femenino , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Locomoción/efectos de los fármacos , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismo , Ratas , Ratas WistarRESUMEN
Chronic stressful stimuli influence disease susceptibility to depression, cardiovascular, metabolic and neurodegenerative disorders. The present work investigated antidepressant and antioxidant properties of the aqueous extract from Cecropia pachystachya in a mouse model of chronic unpredictable stress (CUS). Our results indicated that acute administration of the aqueous extract (AE) from C. pachystachya (200 and 400mg/kg, p.o.) produced an antidepressant-like effect in the forced swimming test (FST). The chronic treatment with C. pachystachya extract (200mg/kg, p.o., for 14 days) prevented the depressant-like effect but not the anxiogenic effect induced by CUS. In addition to the behavioral modifications, the 14 days of CUS increased lipid peroxidation in the hippocampus (HP) and prefrontal cortex (PFC), decreased total thiol content and glutathione peroxidase activity in the HP. C. pachystachya AE administration during CUS protocol was able to prevent the oxidative damage induced by stress. However, no changes were observed in the activity of the antioxidant enzymes superoxide dismutase and catalase in the above cited brain areas after the stress protocol and treatment. Our results suggest that C. pachystachya prevented both depressive behavior and oxidative damage induced by CUS, supporting its neuroprotective potential against behavioral and biochemical dysfunctions induced by chronic stress.
Asunto(s)
Antidepresivos/farmacología , Cecropia , Depresión/prevención & control , Extractos Vegetales/farmacología , Estrés Psicológico/prevención & control , Animales , Antidepresivos/administración & dosificación , Ansiedad/prevención & control , Enfermedad Crónica , Modelos Animales de Enfermedad , Masculino , Ratones , Actividad Motora/efectos de los fármacos , Extractos Vegetales/administración & dosificaciónRESUMEN
The antioxidant properties of two series of thiazolidinones and thiazinanones were reported. The novel six-membered thiazinanones were synthesized from the efficient multicomponent reaction of 2-picolylamine (2-aminomethylpyridine), arenaldehydes, and the 3-mercaptopropionic acid in moderate to excellent yields. These novel compounds were fully identified and characterized by NMR and GC-MS techniques. In vitro antioxidant activities of all compounds were evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) tests. The antioxidant assays of thiobarbituric acid reactive species and total thiol content levels in the cerebral cortex and liver of rats were also performed. Thiazinanone 5a showed the best radical scavenging activity in DPPH and ABTS tests, as well as reduced lipid peroxidation and increased total thiol group in biological systems. Altogether, the results may be considered a good starting point for the discovery of a new radical scavenger.
Asunto(s)
Depuradores de Radicales Libres , Compuestos Heterocíclicos con 3 Anillos , Peroxidación de Lípido/efectos de los fármacos , Animales , Depuradores de Radicales Libres/síntesis química , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología , Compuestos Heterocíclicos con 3 Anillos/síntesis química , Compuestos Heterocíclicos con 3 Anillos/química , Compuestos Heterocíclicos con 3 Anillos/farmacología , Ratas , Ratas WistarRESUMEN
Bipolar disorder (BD) is a chronic and debilitating illness characterized by recurrent manic and depressive episodes. Our research investigates the protective effects of curcumin, the main curcuminoid of the Indian spice turmeric, in a model of mania induced by ketamine administration in rats. Our results indicated that ketamine treatment (25 mg/kg, for 8 days) induced hyperlocomotion in the open-field test and oxidative damage in prefrontal cortex (PFC) and hippocampus (HP), evaluated by increased lipid peroxidation and decreased total thiol content. Moreover, ketamine treatment reduced the activity of the antioxidant enzymes superoxide dismutase and catalase in the HP. Pretreatment of rats with curcumin (20 and 50 mg/kg, for 14 days) or with lithium chloride (45 mg/kg, positive control) prevented behavioral and pro-oxidant effects induced by ketamine. These findings suggest that curcumin might be a good compound for preventive intervention in BD, reducing the episode relapse and the oxidative damage associated with the manic phase of this disorder.
Asunto(s)
Antimaníacos/uso terapéutico , Antioxidantes/uso terapéutico , Trastorno Bipolar/tratamiento farmacológico , Curcumina/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Animales , Antimaníacos/farmacología , Antioxidantes/farmacología , Conducta Animal/efectos de los fármacos , Trastorno Bipolar/inducido químicamente , Trastorno Bipolar/metabolismo , Catalasa/metabolismo , Curcumina/farmacología , Femenino , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Ketamina , Actividad Motora/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismo , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
INTRODUCTION: Green juice is popularly known for introducing antioxidants, improving intestinal function and reducing weight gain. OBJECTIVES: In the present study we determine the antioxidant effect of green juice comparing it with orange juice. METHODS: Rats were divided into three experimental groups and submitted to supplementation for 15 days: the (GJ) group received green juice, the (OJ) group received orange juice and the control group received water. We evaluated the antioxidant activity and total phenolic content of green and orange juices, as well as rat weight gain. We also investigated some oxidative stress parameters, namely thiobarbituric acid-reactive substances (TBARS), superoxide dismutase and catalase in rat cerebral cortex. RESULTS AND DISCUSSION: Results showed that GJ had significantly less weight gain than the control group. With respect to antioxidant activity screening, the remaining percentage of DPPH at dilutions 1:10, 1:100 and 1:1000 of green juice was 22.8%, 58% and 78%, and orange juice, at the same dilutions, was 5.6%, 5.6% and 77.2%, respectively. The ability of juices to reduce the ABTS radical was 3.5 mmol trolox/L for green juice and 5.2 mmol trolox/L for orange juice. Additionally, the green juice did not present any difference in total phenolic acid content when compared to orange juice. TBARS were reduced in GJ and OJ. Besides, GJ supplementation decreased catalase activity. In conclusion, our data showed that green juice reduced weight gain, lipoperoxidation and catalase activity, suggesting that this supplementation may have a protective effect against reactive species.
Introducción: El zumo verde es conocido popularmente como fuente de antioxidantes, mejorando la función intestinal y reduciendo la ganancia de peso. Objetivos: En este estudio determinamos el efecto antioxidante del zumo verde en comparación con el zumo de naranja. Métodos: Se dividió a las ratas en tres grupos experimentales y se las sometió a un suplemento durante 15 días: el grupo ZV recibió zumo verde, el grupo ZN recibió zumo de naranja y el grupo control recibió agua. Evaluamos la actividad antioxidante y el contenido total en fenoles de los zumos verde y de naranja, así como la ganancia de peso en las ratas. También investigamos algunos parámetros del estrés oxidativo, en concreto las sustancias reactivas del ácido tiobarbitúrico (SRATB), la superóxido dismutasa y la catalasa en la corteza cerebral de las ratas. Resultados y discusión: Los resultados mostraron que el ZV producía una ganancia de peso significativamente menor que en el grupo control. Con respecto al estudio de la actividad antioxidante, el porcentaje restante de DPPH en diluciones al 1:10, 1:100 y 1:1000 de zumo verde fue del 22,8%, 58% y 78%, y para el zumo de naranja, a las mismas diluciones, fue del 5,6%, 5,6% y 77,2%, respectivamente. La capacidad de los zumos para reducir el radical de ATB fue de 3,5 mmol trolox/l para el zumo verde y de 5,2 mmol trolox/l para el zumo de naranja. Adicionalmente, el zumo verde no mostró ninguna diferencia en el contenido total de ácido fenólico en comparación con el zumo de naranja. Las SRATB se redujeron con el ZV y el ZN. Además, el suplemento con ZV disminuyó la actividad catalasa. En conclusión, nuestros datos mostraron que el zumo verde redujo la ganancia de peso, la lipoperoxidación y la actividad catalasa, lo que sugiere que este suplemento podría tener un efecto protector frente a las especies reactivas.
Asunto(s)
Antioxidantes , Bebidas , Citrus sinensis , Alimentos Funcionales , Animales , Masculino , Ratas , Ratas Wistar , Especies Reactivas de OxígenoRESUMEN
INTRODUCTION: Green juice is popularly known for introducing antioxidants, improving intestinal function and reducing weight gain. OBJECTIVES: In the present study we determine the antioxidant effect of green juice comparing it with orange juice. METHODS: Rats were divided into three experimental groups and submitted to supplementation for 15 days: the (GJ) group received green juice, the (OJ) group received orange juice and the control group received water. We evaluated the antioxidant activity and total phenolic content of green and orange juices, as well as rat weight gain. We also investigated some oxidative stress parameters, namely thiobarbituric acid-reactive substances (TBARS), superoxide dismutase and catalase in rat cerebral cortex. RESULTS AND DISCUSSION: Results showed that GJ had significantly less weight gain than the control group. With respect to antioxidant activity screening, the remaining percentage of DPPH at dilutions 1:10, 1:100 and 1:1000 of green juice was 22.8%, 58% and 78%, and orange juice, at the same dilutions, was 5.6%, 5.6% and 77.2%, respectively. The ability of juices to reduce the ABTS radical was 3.5 mmol trolox/L for green juice and 5.2 mmol trolox/L for orange juice. Additionally, the green juice did not present any difference in total phenolic acid content when compared to orange juice. TBARS were reduced in GJ and OJ. Besides, GJ supplementation decreased catalase activity. In conclusion, our data showed that green juice reduced weight gain, lipoperoxidation and catalase activity, suggesting that this supplementation may have a protective effect against reactive species (AU)
Introducción: El zumo verde es conocido popularmente como fuente de antioxidantes, mejorando la función intestinal y reduciendo la ganancia de peso. Objetivos: En este estudio determinamos el efecto antioxidante del zumo verde en comparación con el zumo de naranja. Métodos: Se dividió a las ratas en tres grupos experimentales y se las sometió a un suplemento durante 15 días: el grupo ZV recibió zumo verde, el grupo ZN recibió zumo de naranja y el grupo control recibió agua. Evaluamos la actividad antioxidante y el contenido total en fenoles de los zumos verde y de naranja, así como la ganancia de peso en las ratas. También investigamos algunos parámetros del estrés oxidativo, en concreto las sustancias reactivas del ácido tiobarbitúrico (SRATB), la superóxido dismutasa y la catalasa en la corteza cerebral de las ratas. Resultados y discusión: Los resultados mostraron que el ZV producía una ganancia de peso significativamente menor que en el grupo control. Con respecto al estudio de la actividad antioxidante, el porcentaje restante de DPPH en diluciones al 1:10, 1:100 y 1:1000 de zumo verde fue del 22,8%, 58% y 78%, y para el zumo de naranja, a las mismas diluciones, fue del 5,6%, 5,6% y 77,2%, respectivamente. La capacidad de los zumos para reducir el radical de ATB fue de 3,5 mmol trolox/l para el zumo verde y de 5,2 mmol trolox/l para el zumo de naranja. Adicionalmente, el zumo verde no mostró ninguna diferencia en el contenido total de ácido fenólico en comparación con el zumo de naranja. Las SRATB se redujeron con el ZV y el ZN. Además, el suplemento con ZV disminuyó la actividad catalasa. En conclusión, nuestros datos mostraron que el zumo verde redujo la ganancia de peso, la lipoperoxidación y la actividad catalasa, lo que sugiere que este suplemento podría tener un efecto protector frente a las especies reactivas (AU)
Asunto(s)
Animales , Ratas , Zumos , Antioxidantes/farmacocinética , Estrés Oxidativo , Especies Reactivas de Oxígeno , Modelos Animales , Aumento de Peso , Peroxidación de Lípido , Catalasa/antagonistas & inhibidoresRESUMEN
In the present study, we reported the efficient synthesis of 11 3-(pyrimidin-2-yl)-thiazolidinones in good yields using molecular sieve as the desiccant agent. In addition, we have evaluated the antioxidant capacity of the synthesized compounds by the 2,2-diphenyl-2-picrylhydrazyl hydrate (DPPHâ¢) and the 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS(+â¢) ) radicals scavenging assay. Six compounds showed antioxidant activity towards DPPH⢠(EC50 between 16.13 and 49.94 µg/mL) and also demonstrated excellent activity regarding ABTS(+â¢) (TEAC: 10.32-53.52). These results showed that compounds 3-(pyrimidin-2-yl)-thiazolidinones may be easily synthesized by a less expensive procedure and could be a good starting point to the development of new antioxidant compounds.
Asunto(s)
Antioxidantes/química , Antioxidantes/síntesis química , Pirimidinas/química , Tiazolidinas/química , Tiazolidinas/síntesis química , Benzotiazoles/química , Depuradores de Radicales Libres/química , Oxidación-Reducción , Ácidos Sulfónicos/químicaRESUMEN
The Biginelli reaction is a multicomponent reaction involving the condensation between an aldehyde, a ß-ketoester, and urea or thiourea, in the presence of an acid catalyst, producing dihydropyrimidinones (DHPMs). Owing to their important pharmacological properties, the DHPMs have been studied by many authors. However, most of the methodologies used for the synthesis of these compounds require drastic reaction conditions. In the current study, we report an efficient and clean procedure for preparing DHPMs by the use of citric acid or tartaric acid as a promoter of the Biginelli synthesis in ethanol as solvent. In addition, we have evaluated the antioxidant capacity of the compounds synthesized by the 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay and the thiobarbituric acid-reactive species test. Two compounds presented antioxidant activity and also reduced lipid peroxidation at concentrations of 200 and 300 µM. In summary, we report an environmentally friendly procedure for the preparation of DHPMs and demonstrate the antioxidant capacity of some of the compounds.
Asunto(s)
Antioxidantes/síntesis química , Ácido Cítrico/química , Pirimidinonas/síntesis química , Tartratos/química , Animales , Antioxidantes/química , Antioxidantes/farmacología , Etanol/química , Peroxidación de Lípido/efectos de los fármacos , Pirimidinonas/química , Pirimidinonas/farmacología , Ratas , Ratas Wistar , Solventes/químicaRESUMEN
Considering that Na(+),K(+)-ATPase is an embedded-membrane enzyme and that experimental chronic hyperprolinemia decreases the activity of this enzyme in brain synaptic plasma membranes, the present study investigated the effect of chronic proline administration on thiobarbituric acid-reactive substances, as well as the influence of antioxidant vitamins E plus C on the effects mediated by proline on Na(+),K(+)-ATPase activity in cerebral cortex of rats. The expression of Na(+),K(+)-ATPase catalytic subunits was also evaluated. Results showed that proline increased thiobarbituric acid-reactive substances, suggesting an increase of lipid peroxidation. Furthermore, concomitant administration of vitamins E plus C significantly prevented the increase of lipid peroxidation, as well as the inhibition of Na(+),K(+)-ATPase activity caused by proline. We did not observe any change in levels of Na(+),K(+)-ATPase mRNA transcripts after chronic exposure to proline and vitamins E plus C. These findings provide insights into the mechanisms through which proline exerts its effects on brain function and suggest that treatment with antioxidants may be beneficial to treat neurological dysfunctions present in hyperprolinemic patients.
Asunto(s)
Antioxidantes , Ácido Ascórbico , Corteza Cerebral/enzimología , Peroxidación de Lípido/efectos de los fármacos , ATPasa Intercambiadora de Sodio-Potasio/efectos de los fármacos , Vitamina E , 1-Pirrolina-5-Carboxilato Deshidrogenasa/deficiencia , Errores Innatos del Metabolismo de los Aminoácidos/inducido químicamente , Errores Innatos del Metabolismo de los Aminoácidos/metabolismo , Análisis de Varianza , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Ácido Ascórbico/metabolismo , Ácido Ascórbico/farmacología , Corteza Cerebral/efectos de los fármacos , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Expresión Génica/efectos de los fármacos , Humanos , Estrés Oxidativo/efectos de los fármacos , Prolina/administración & dosificación , Prolina/efectos adversos , Prolina Oxidasa/deficiencia , Prolina Oxidasa/metabolismo , Ratas , Ratas Wistar , ATPasa Intercambiadora de Sodio-Potasio/antagonistas & inhibidores , Membranas Sinápticas/efectos de los fármacos , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Vitamina E/metabolismo , Vitamina E/farmacologíaRESUMEN
In the current study we initially investigated the influence of antioxidants (vitamins E plus C) on the effect mediated by acute and chronic administration of methionine (Met) on Na(+),K(+)-ATPase activity in rat hippocampus. We also verified whether the alterations on the enzyme after administration of Met and/or antioxidants were associated with changes in relative expression of Na(+),K(+)-ATPase catalytic subunits (isoforms α1, α2 and α3). For acute treatment, young rats received a single subcutaneous injection of Met or saline (control) and were sacrificed 12 h later. In another set of experiments, rats were pretreated for 1 week with daily intraperitoneal administration of vitamins E (40 mg/kg) and C (100 mg/kg) or saline. After that, rats received a single injection of Met or saline and were killed 12 h later. For chronic treatment, Met was administered to rats from the 6th to the 28th day of life; controls and treated rats were sacrificed 12 h after the last injection. In parallel to chronic treatment, rats received a daily intraperitoneal injection of vitamins E and C from the 6th to the 28th day of life and were killed 12 h after the last injection. Results showed that administration of antioxidants partially prevented the inhibition of enzyme activity caused by acute and chronic hypermethioninemia. Besides, we demonstrated that transcription of catalytic subunits of Na(+),K(+)-ATPase was not altered by chronic and acute exposure to Met and/or vitamins E plus C. These data strongly suggest the oxidative damage as one possible mechanism involved in the reduction of Na(+),K(+)-ATPase activity caused by hypermethioninemia and if confirmed in human beings, we might propose the use of antioxidants as an adjuvant therapy in hypermethioninemic patients.
Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/metabolismo , Errores Innatos del Metabolismo de los Aminoácidos/prevención & control , Antioxidantes/farmacología , Ácido Ascórbico/farmacología , Hipocampo/efectos de los fármacos , Hipocampo/enzimología , Metionina/sangre , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Vitamina E/farmacología , Enfermedad Aguda , Errores Innatos del Metabolismo de los Aminoácidos/enzimología , Animales , Enfermedad Crónica , Humanos , Ratas , Ratas WistarRESUMEN
We have previously demonstrated that early environment influences the metabolic response, affecting abdominal fat deposition in adult female rats exposed to a long-term highly caloric diet. In the present study, our goal was to verify the effects of the chronic exposure, in adulthood, to a highly palatable diet (chocolate) on cerebral Na+,K+-ATPase activity and S100B protein concentrations, and the response to its withdrawal in neonatally handled and non-handled rats. We measured the consumption of foods (standard lab chow and chocolate), body weight gain, S100B protein concentrations, as well as cerebral Na(+),K(+)-ATPase activity during chronic exposure and after chocolate withdrawal in adult female rats that had been exposed or not to neonatal handling (10 min/day, 10 first days of life). Non-handled rats chronically exposed to chocolate exhibited increased plasma S100B levels, but there was no difference in abdominal fat S100B concentration between groups. Chronic chocolate consumption decreased Na+,K+-ATPase activity in both amygdala and hippocampus in non-handled, but not in handled rats, and this effect disappeared after chocolate withdrawal. Non-handled animals also demonstrated increased frequency of head shaking in the open field after 24h of chocolate withdrawal in comparison to handled ones. These findings suggest that neonatal handling modifies the vulnerability to metabolic and brain alterations induced by chronic exposure to a highly palatable diet in adulthood.