RESUMO
Hyperlipidemia causes lipotoxicity which prompts an inflammatory response linked to the development of cardiovascular diseases. Natural compounds have been receiving special attention for its potential to treat diseases, inexpensiveness, and safety. Guarana (Paullinia cupana) has demonstrated notable anti-inflammatory and antioxidant effects, which may prevent chronic diseases caused by changes in lipid profile. Thus, this study aims to evaluate the effect of guarana powder (Paullinia cupana) in the purine metabolism and inflammatory profile in lymphocytes and serum of rats with Poloxamer-407-induced hyperlipidemia. Pretreatment with guarana 12.5, 25, and 50 mg/kg/day or caffeine (0.2 mg/kg/day) by gavage was applied to adult male Wistar rats for a period of 30 days. As a comparative standard, we used simvastatin (0.04 mg/kg) post-induction. Hyperlipidemia was acutely induced with intraperitoneally injection of Poloxamer-407 (500 mg/kg). Guarana powder and caffeine increased the activity of the E-NTPDase (ecto-apyrase), and all pretreatments decreased the E-ADA (ecto-adenosine deaminase) activity, reducing the inflammatory process caused by lipotoxicity. In hyperlipidemic rats, ATP levels were increased while adenosine levels were decreased, guarana and caffeine reverted these changes. Guarana powder, caffeine, and simvastatin also prevented the increase in INF-γ and potentiated the increase in IL-4 levels, promoting an anti-inflammatory profile. Guarana promoted a more robust effect than caffeine. Our results show that guarana powder and caffeine have an anti-inflammatory as seen by the shift from a proinflammatory to an anti-inflammatory profile. The effects of guarana were more pronounced, suggesting that guarana powder may be used as a complementary therapy to improve the lipotoxicity-associated inflammation.
Assuntos
Anti-Inflamatórios/farmacologia , Cafeína/farmacologia , Hiperlipidemias/tratamento farmacológico , Inflamação/prevenção & controle , Teobromina/farmacologia , Teofilina/farmacologia , Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Anti-Inflamatórios/administração & dosagem , Cafeína/administração & dosagem , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Hiperlipidemias/fisiopatologia , Inflamação/etiologia , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Masculino , Ratos , Ratos Wistar , Sinvastatina/farmacologia , Teobromina/administração & dosagem , Teofilina/administração & dosagemRESUMO
The effects of Toxoplasma gondii during embryonic development have not been explored despite the predilection of this parasite for neurons and glial cells. Here, we investigated the activation of the purinergic system and proinflammatory responses during congenital infection by T. gondii. Moreover, neuroprotective and neuromodulatory properties of resveratrol (RSV), a polyphenolic natural compound, were studied in infected neuronal progenitor cells (NPCs). For this study, NPCs were isolated from the telencephalon of infected mouse embryos and subjected to neurosphere culture in the presence of EGF and FGF2. ATP hydrolysis and adenosine deamination by adenosine deaminase activity were altered in conditions of T. gondii infection. P2X7 and adenosine A2A receptor expression rates were augmented in infected NPCs together with an increase of proinflammatory (INF-γ and TNF-α) and anti-inflammatory (IL-10) cytokine gene expression. Our results confirm that RSV counteracted T. gondii-promoted effects on enzymes hydrolyzing extracellular nucleotides and nucleosides and also upregulated P2X7 and A2A receptor expression and activity, modulating INF-γ, TNF-α, and IL-10 cytokine production, which plays an integral role in the immune response against T. gondii.
Assuntos
Antioxidantes/farmacologia , Células-Tronco Neurais , Receptor A2A de Adenosina/metabolismo , Receptores Purinérgicos P2X7/metabolismo , Resveratrol/farmacologia , Toxoplasmose/metabolismo , Animais , Feminino , Camundongos , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/imunologia , Células-Tronco Neurais/microbiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/microbiologia , Purinas/metabolismo , Receptor A2A de Adenosina/imunologia , Receptores Purinérgicos P2X7/imunologia , Toxoplasmose/imunologiaRESUMO
OBJECTIVE: Serotonin (5-HT) is a pleiotropic molecule that exerts several functions on brain and peripheral tissues via different receptors. The gene for the 5-HT2A receptor shows some variations, including a T102C polymorphism, that have been associated with increased risk of neuropsychiatric and vascular disorders. However, the potential impact of 5-HT2A imbalance caused by genetic variations on the human lifespan has not yet been established. METHODS: We performed a prospective study involving an Amazon riparian elderly free-living population in Maués City, Brazil, with a 5-year follow-up. Out of a cohort of 637 subjects selected in July, 2009, we genotyped 471 individuals, including 209 males (44.4%) and 262 females (55.6%), all averaging 72.3 ± 7.8 years of age (ranging from 60 to 100 years). RESULTS: The T102C-SNP genotypic frequencies were 14.0% TT, 28.0% CC, and 58.0% CT. From 80 elderly individuals who died during the period investigated, we observed significantly (P = .005) higher numbers of TT carriers (27.3%) and CC carriers (21.2%), compared to heterozygous CT carriers (12.5%). Cox-regression analysis showed that association between the T102C-SNP and elderly survival was independent of age, sex, and other health variables. CONCLUSIONS: Our findings strongly suggest that imbalance in 5-HT2A may cause significant disturbances that lead to an increased susceptibility to death for individuals who are over 60 years of age.
Assuntos
Mortalidade , Polimorfismo Genético , Receptor 5-HT2A de Serotonina/genética , Idoso , Idoso de 80 Anos ou mais , Brasil , Cidades , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Receptor 5-HT2A de Serotonina/metabolismo , RiscoRESUMO
Objective To ascertain whether modifiable physical performance-based measurements predicted 5.5-year mortality in a riparian elderly cohort in the Amazon rainforest region. Methods A longitudinal study evaluating the impact of functional determinants on 5.5-year mortality in a riparian elderly cohort from Maués City in the state of Amazonas, Brazil, was performed. The study was a follow-up of a previous observational investigation that evaluated various fitness tests in 630 Amazonian riparian elderly (291 males and 339 females) aged 72.3 ± 8.0 (60-99) years old. The cohort was selected for its adverse environmental conditions, which increased the risk of falls yet required maintenance of good physical condition for carrying out relatively rigorous daily activities, and restricted access to specialized health services. Official death records were obtained from the Maués Municipal Health Department. Results A total of 80 study participants (12.7%) died over the 5.5-year study period. Kaplan-Meier regression analysis showed significant association between Timed Up and Go (TUG) test scores ≥ 14 seconds and mortality risk, independent of sex, age, and other health variables. Conclusions The study results suggest that the TUG test can be used as an indicator for initiating therapeutic and preventive actions, including conducting exercises or physical activities adapted to the health and functional conditions of the elderly, by identifying elderly people with a higher relative risk of mortality.
Assuntos
Atividades Cotidianas , Mortalidade , Aptidão Física , Idoso , Idoso de 80 Anos ou mais , Brasil , Exercício Físico , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Estimativa de Kaplan-Meier , Estudos Longitudinais , Masculino , RiscoRESUMO
The COVID-19 pandemic had a great impact on the mortality of older adults and, chronic non- transmissible diseases (CNTDs) patients, likely previous inflammaging condition that is common in these subjects. It is possible that functional foods could attenuate viral infection conditions such as SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the causal agent of COVID-19 pandemic. Previous evidence suggested that some fruits consumed by Amazonian Diet from Pre-Colombian times could present relevant proprieties to decrease of COVID-19 complications such as oxidative-cytokine storm. In this narrative review we identified five potential Amazonian fruits: açai berry (Euterpe oleracea), camu-camu (Myrciaria dubia), cocoa (Theobroma cacao), Brazil nuts (Bertholletia excelsa), and guaraná (Paullinia cupana). Data showed that these Amazonian fruits present antioxidant, anti-inflammatory and other immunomodulatory activities that could attenuate the impact of inflammaging states that potentially decrease the evolution of COVID-19 complications. The evidence compiled here supports the complementary experimental and clinical studies exploring these fruits as nutritional supplement during COVID-19 infection. PRACTICAL APPLICATIONS: These fruits, in their natural form, are often limited to their region, or exported to other places in the form of frozen pulp or powder. But there are already some companies producing food supplements in the form of capsules, in the form of oils and even functional foods enriched with these fruits. This practice is common in Brazil and tends to expand to the international market.
Assuntos
COVID-19 , Euterpe , Humanos , Idoso , Frutas , Pandemias , SARS-CoV-2 , AntioxidantesRESUMO
The MnSOD Ala16Val single nucleotide polymorphism (SNP) has shown to be associated to risk factors of several metabolic and vascular diseases. However, little is known about interaction between MnSOD Ala16Val SNP in stroke, a frequent neurologic disease that involves clinic manifestations such as motor deficits and spasticity. In this sense, we decided to investigate the relationship between MnSOD Ala16Val SNP with spasticity in stroke and also its influence on interleukin levels, BDNF, and glycolipid parameters. Eighty post-stroke subjects and 80 healthy controls were investigated. We showed a higher spasticity, levels of total cholesterol, LDL, IL-1ß, IL-6, and INF-γ in VV post-stroke group. Interesting, we found a correlation between IL-1ß levels and spasticity in VV post-stroke. Triglycerides, glucose levels and caspases (1 and 3) activation were significantly higher, as well as BDNF levels were lower in VV and AV post-stroke. DNA damage was higher in post-stroke group. Thus, we can suggest that the V allele has a worse glycolipid profile, which would facilitate changes in neurovascular homeostasis. These events associated with an increase in inflammatory markers and a reduction in BDNF can contribute with the stroke and a worse clinical evolution in relation to spasticity in patients with VV genotype.
Assuntos
Interleucina-6 , Acidente Vascular Cerebral , Fator Neurotrófico Derivado do Encéfalo/genética , Caspases/genética , LDL-Colesterol/genética , Genótipo , Glucose , Glicolipídeos , Humanos , Interleucina-1beta/genética , Interleucina-6/genética , Espasticidade Muscular/genética , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/genética , Superóxido Dismutase/genética , TriglicerídeosRESUMO
Background: Previous studies have suggested that guarana (Paullinia cupana) and açai (Euterpe oleracea) have antioxidant, anti-inflammatory, and proliferative properties, indicating their potential therapeutic action in wound healing. We produced a conjugated guarana-açai (GA) extract and tested its healing action on earthworms (Eisenia fetida) subjected to tail amputation by surgical incision. Methods: Extract from roasted guarana seeds and fresh açai seed berries was produced. The antioxidant and genoprotective capacity of GA extract was tested. The concentration with the most remarkable healing potential was used in subsequent tests. The last three posterior segments of the clitellate earthworm tail reared under standardized conditions were surgically amputated. Next, topical PBS or GA extract was applied to the surgical wound. The rate of cell migration and tissue regeneration at the local wound site was histologically evaluated after the procedure. Expression of the SOX4 gene that acts in epithelial-to-mesenchymal transition was determined by RT-qPCR. Results: Sixteen bioactive molecules, including some previously described substances, were identified. All tested concentrations exhibited antioxidant and genoprotective effects. The GA extract accelerated the healing processes as observed through macroscopic and histological analyses and increased expression of SOX4. Conclusion: The GA extract has a potential role in the healing of surgically induced wounds.
Assuntos
Oligoquetos , Paullinia , Amputação Cirúrgica , Animais , Antioxidantes/farmacologia , Fibroblastos , Estresse Oxidativo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , CicatrizaçãoRESUMO
BACKGROUND: Açaí (Euterpe oleracea Mart), a Brazilian fruit, is considered a "superfruit" due its energetic properties and bioactive compounds. The açai's anti-inflammatory effects could attenuate the undesirable metabolic and pro-inflammatory side effects triggered by some antipsychotic drugs, such as Olanzapine (OLZ). It is possible to infer that açai supplement could potentially minimize the adverse effects of OLZ. Aim. This study tested the potential in vitro effects of açai hydroalcoholic extract on the inflammatory activation of the RAW 264.7 macrophage line triggered by OLZ antipsychotic drugs. METHODS: An in vitro protocol was performed using commercial RAW 264.7 macrophages, cultured under sterile conditions at 37°C with 5% CO2 saturation. Initially, a pharmacological curve was defined to determine the concentration of Olanzapine to be used. After this, the cells were supplemented with different concentrations of hydroalcoholic extract of açaí, which had been previously chemically characterized. After 24 and 72 hours of treatment, oxidative and inflammatory tests were performed. Therefore, the aim of this study was to verify whether the hydroalcoholic extract of açaí can modulate the oxy-inflammatory response of olanzapine in vitro. RESULTS: From a preliminary analysis, the açai extract at 5 mg/mL presented higher activity against inflammation triggered by OLZ (0.03 µg/mL). At this concentration, açai was able to reduce several oxidative and inflammatory markers triggered by OLZ (0.03 µg/mL) exposure, such as nitric oxide (NO), reactive oxygen species (ROS), and pro-inflammatory cytokine levels (IL-1b, IL-6, TNF-a, IFN-g) caused by OLZ (0.03 µg/mL). Moreover, açaí reverted the levels of anti-inflammatory cytokine IL-10 that had been dropped by OLZ exposure to their pre-exposure treatments. CONCLUSIONS: The results suggest that açai extract could be useful in attenuating the peripheral inflammatory states triggered by OLZ. Additional pre-clinical and clinical investigations could be useful in testing therapeutic açai extract supplements.
Assuntos
Anti-Inflamatórios/uso terapêutico , Antipsicóticos/efeitos adversos , Euterpe/química , Inflamação/prevenção & controle , Olanzapina/efeitos adversos , Fitoterapia , Extratos Vegetais/uso terapêutico , Animais , Antocianinas/análise , Antocianinas/farmacologia , Antocianinas/uso terapêutico , Anti-Inflamatórios/análise , Anti-Inflamatórios/farmacologia , Antioxidantes/análise , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Citocinas/metabolismo , Suplementos Nutricionais , Frutas/química , Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , alfa-Tocoferol/análise , alfa-Tocoferol/farmacologia , alfa-Tocoferol/uso terapêuticoRESUMO
Neurodegenerative diseases are associated with chronic inflammatory states. There is evidence to support the design of novel supplements based on guarana (G) (Paullinia cupana), selenium (S), and L-carnitine (C), the use of which, potentially attenuates neuro oxi-inflammatory conditions. Therefore, this study analyzed the cytotoxic and redox effects of GSC on human leucocytes, the inflammatory activation of microglia BV-2 cells, and effect on mortality, oxidative metabolism, and the immune modulation of red earthworms (Eisenia fetida). The GSC concentrations tested in cell culture were in the range of 0.04-2.1 mg/mL. All the GSC-supplemented samples tested, reverted H2O2 oxidation in DNA molecules, suggesting its genoprotective potential. GSC did not induce mortality in leucocyte cultures. On the contrary, a reduction in the levels of oxidation of lipids, proteins, and cell apoptosis was observed, via downregulation of caspase 3 and 8 genes. GSC showed a dual effect on microglia, decreasing the cellular proliferation at lower concentrations (<0.24 mg/mL) and increasing the cellular proliferation mainly at concentrations > 1.0 mg/mL. GSC did not have a toxic effect on red earthworms, but induced an increase in amoebocyte cells and in brown body formation, indicating immune response activation. The results suggest that GSC could be safe for human consumption.
Assuntos
Carnitina/farmacologia , Eimeria/efeitos dos fármacos , Paullinia , Selênio/farmacologia , Carnitina/química , Ciclo Celular , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Humanos , Peroxidação de Lipídeos , Microglia , Oxirredução , Selênio/químicaRESUMO
Paullinia cupana var. sorbilis (Mart.) Ducke, popularly known as guarana, is one of the most promising plants in Brazilian flora and has attracted considerable interest from the scientific community owing to its numerous therapeutic activities and less side effects. Hence, using nanotechnology is a viable alternative to primarily improve the physicochemical characteristics and bioavailability of guarana. The objective of the present study was to develop, characterize, and evaluate the stability of liposomes containing guarana powder and to evaluate their antioxidant and hemolytic activity in vitro. Three different concentrations of guarana powder and two methods of liposome preparation were tested. Liposomes were developed and characterized, and their stability was analyzed by evaluating physicochemical parameters. Hemolytic activity of guarana liposomal formulation (G-Lip) was compared with that of guarana in its free form (FG) and of liposome without guarana (W-Lip). Red blood cells from rats were exposed to these different formulations dissolved in phosphate buffer solution (PBS; pH 7.4). The best stability was achieved for the formulation containing 1 mgâ¯mL-1 guarana powder produced by the reverse phase evaporation method. FG showed dose-dependent antioxidant activity, which was maintained in G-Lip. W-Lip showed high hemolytic activity in PBS at pH 7.4 possibly because of the presence of polysorbate 80, and on addition of guarana to these structures, the hemolytic process was reversed. The same protective effect was observed for FG. It is believed that the complex structure of guarana, primarily the presence of polyphenols, exerts a powerful antioxidant action, helping to protect erythrocytes.
Assuntos
Cafeína/farmacologia , Hemólise/efeitos dos fármacos , Lipossomos/química , Substâncias Protetoras/farmacologia , Teobromina/farmacologia , Teofilina/farmacologia , Animais , Antioxidantes/farmacologia , Composição de Medicamentos , Lipossomos/ultraestrutura , Tamanho da Partícula , RatosRESUMO
Aging accelerates neurodegeneration, while natural and safe neuroprotective agents, such as Uncaria tomentosa, may help to overcome this problem. This study assessed the effects of U. tomentosa extract treatment on the aging process in the brain of Wistar rats. The spatial memory and learning, acetylcholinesterase (AChE) activity, and DNA damage were assessed. Animals of 14 months were tested with different doses of U. tomentosa (5 mg/kg, 15 mg/kg, and 30 mg/kg) and with different durations of treatment (one month and one year). In the Morris Water Maze (MWM), the escape latency was significantly (p < 0.0001) shorter in rats that received 5 mg/kg, 15 mg/kg, and 30 mg/kg of U. tomentosa for both one month and one year of treatment. There was a significant difference in time spent at the platform zone (p < 0.05) of the middle-aged rats treated with U. tomentosa extract for one year when compared to the control rats. The cortex and hippocampus of rats treated with U. tomentosa for one year showed significant (p > 0.05) reduction in AChE activity. DNA damage index on cortex was significantly lower (p < 0.05) in animals treated with 30 mg/kg of U. tomentosa for one month while all the tested doses demonstrated significant (p < 0.001) reductions in DNA damage index in animals treated for one year. In conclusion, U. tomentosa may represent a source of phytochemicals that could enhance memory activity, repair DNA damage, and alter AChE activity, thereby providing neuroprotection during the aging process.
Assuntos
Unha-de-Gato , Animais , Antioxidantes , Cognição , Extratos Vegetais/farmacologia , Ratos , Ratos WistarRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The fruit of Astrocaryum aculeatum G.Mey. (tucumã) is highly consumed by riverside communities in the Amazonian region. These communities have recently been shown to have increased longevity and reduced prevalence of age-related morbidity. Tucumã, which is locally used in their diet and traditional medicine may contribute to these features. AIM OF THE STUDY: To investigate the anti-inflammatory and antioxidant properties of A. aculeatum extract against phytohemagglutinin-induced inflammation in cell cultures. MATERIALS AND METHODS: Cell viability and cytotoxicity assays, gene expression of interleukins IL-1ß, IL-6, IL-10, levels of reactive oxygen species (ROS), nitric oxide (NO) and thiols were employed, as well as the activities of antioxidant enzymes in RAW 264.7â¯cells stimulated with phytohemagglutinin to mimic inflammation. RESULTS: The extract of A. aculeatum fruit inhibited macrophage proliferation (Pâ¯<â¯0.05), arrested the cell cycle in G0/G1 phase (Pâ¯<â¯0.001), increased antioxidant defenses (Pâ¯<â¯0.01), reduced oxidative stress (Pâ¯<â¯0.01), and modulated genes related to the inflammatory response (Pâ¯<â¯0.001). CONCLUSION: Our results demonstrate that A. aculeatum fruit has anti-inflammatory and antioxidant capacities. These beneficial effects of tucumã on cells are also likely to be seen in vivo, thereby suggesting that its extract is a suitable therapeutic adjuvant in the prevention or treatment of inflammatory diseases.
Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Arecaceae/química , Inflamação/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/uso terapêutico , Antioxidantes/isolamento & purificação , Antioxidantes/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Etnofarmacologia , Frutas/química , Inflamação/imunologia , Medicina Tradicional , Camundongos , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/imunologia , Fito-Hemaglutininas/imunologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Plantas Comestíveis/química , Células RAW 264.7 , América do SulRESUMO
The MnSOD Ala16Val single nucleotide polymorphism (SNP) has shown to be associated to inflammatory pathways and many metabolic disorders, such as obesity and dyslipidemia. Metabolic syndrome (MetS) is an emergent problem among patients with epilepsy. However, little is known about interaction between MnSOD Ala16Val SNP and metabolic comorbities in epilepsy. Thus, we investigated the relationship between MnSOD Ala16Val SNP with epilepsy and its influence on MetS, inflammation, apoptosis and DNA damage parameters. Ninety subjects were evaluated (47 epilepsy patients and 43 healthy controls) by questionnaires and laboratorial exams. Levels of inflammatory, apoptotic and DNA damage markers, as well as MnSOD polymorphism were assessed. An increased proportion of VV genotype in epilepsy group when compared to control group was observed. Tumor Necrosis Factor-α (TNF-α), Acetylcholinesterase, caspase-8, and Picogreen levels were increased in VV epilepsy group. An important correlation between TNF-α vs caspase-8, and Cholesterol vs. Triglycerides was observed in the epilepsy group with VV genotype. Our findings suggest that the MnSOD Ala16Val SNP might have an important role in epilepsy, mainly in patients with generalized seizures and particularly with VV genotype. The metabolic parameters also presented significant results in epilepsy group with VV genotype, which applying attention in view of further consequences and disorders that could be developed.
Assuntos
Substituição de Aminoácidos , Colesterol/metabolismo , Convulsões/genética , Superóxido Dismutase/genética , Triglicerídeos/metabolismo , Acetilcolinesterase/genética , Adulto , Estudos de Casos e Controles , Caspase 8/genética , Dano ao DNA , Feminino , Proteínas Ligadas por GPI/genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Estresse Oxidativo , Fator de Necrose Tumoral alfa/genéticaRESUMO
Uric acid presents different roles in an organism, since it can act as an antioxidant or a pro-oxidant molecule. High serum uric acid levels may cause damage to several structures, including nucleic acids and its components. Therefore, in this study the association between increased serum uric acid concentrations and oxidation of nucleosides was investigated by assessment of urinary 8-hydroxydeoxyguanosine (8-OHdG) in patients with type 2 diabetes (T2D) and in healthy individuals. Urinary 8-OHdG and biochemical parameters were assessed in 61 patients who were initially grouped into 2 groups based on the median serum uric acid levels (<5.3 mg/dL and ≥5.3 mg/dL). Urinary 8-OHdG was higher in patients with T2D and serum uric acid levels ≥5.3 mg/dL, when compared with the patients with serum uric acid levels <5.3 mg/dL; however, co-occurrence of high serum uric acid with high urinary 8-OHdG was not observed in healthy individuals. A significant positive correlation between 8-OHdG and uric acid (r = 0.40, P < 0.01) was observed in patients with T2D. High serum uric acid levels were associated with high urinary 8-OHdG levels in patients with T2D, and this association was independent of gender, hypertension, body mass index, and serum creatinine.
Assuntos
Desoxiguanosina/análogos & derivados , Diabetes Mellitus Tipo 2/metabolismo , Nucleosídeos/metabolismo , Ácido Úrico/sangue , 8-Hidroxi-2'-Desoxiguanosina , Adulto , Idoso , Creatinina/sangue , Desoxiguanosina/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , OxirreduçãoRESUMO
INTRODUCTION: Lithium (Li), a mood stabilizer used to treat bipolar disorder (BP) symptoms has important anti-inflammatory effects by downregulation of glycogen synthase kinase-3 beta (GSK-3ß). However, sometime Li effect is not efficient in some patients suggesting genetic interference. Previous investigations described association between a genetic superoxidehydrogen (S-HP) imbalance caused by a superoxide dismutase manganese dependent gene polymorphism (Val16Ala-SOD2 SNP, rs4880) and differential anti-inflammatory response of some drugs and bioactive molecules. Therefore, we postulated here that S-HP imbalance could present some effect on GSK-3ß modulation by Li. METHODS: to test this hypothesis, a genetic and a pharmacological S-HP imbalance protocols were performed. In the two protocols, immune cells were activated by phythohemaglutin (PHA). The first one, used peripheral blood mononuclear cells (PBMCs) cultures carrying different Val16Ala-SOD2 genotypes, and the second used a commercial macrophage cell line RAW 264.7. Macrophages were exposed to paraquat to induce high S levels (VV-like cells) or porphyrin, that is a SOD2-like molecule that increase dismutation of S into HP (AA-like cells). In both protocols the Li effects on GSK-3ß gene and protein modulation as evaluated in 24â¯h cultures. The inflammatory activation was also analyzed by cellular proliferation in 72â¯h cell cultures. RESULTS: as expected PHA exposure triggered a strong upregulation of GSK-3ß gene expression (pâ¯≤â¯0.001), and Li exposure showed GSK-3ß gene downregulation from 0.7â¯mEq/L concentrations. However, Li modulatory effects on GSk-3ß gene and protein expression was directly influenced by basal S-HP balance. Presence of high S-basal levels (VV genotype and VV-like cells) induced attenuated Li anti-inflammatory effects in comparison with balanced and AA and AA-like cells (pâ¯<â¯0.001). Despite methodological limitations related to in vitro assays, the whole of results suggested that Li anti-inflammatory effects is influenced by S-HP basal state and is plausible that its influence could contributes to resistance of some patients to Li treatment or to increase of intensity of some side effects Li-associated.
Assuntos
Glicogênio Sintase Quinase 3 beta/metabolismo , Peróxido de Hidrogênio/metabolismo , Lítio/farmacologia , Estresse Oxidativo , Superóxidos/metabolismo , Adolescente , Adulto , Animais , Transtorno Bipolar/sangue , Transtorno Bipolar/imunologia , Células Cultivadas , Glicogênio Sintase Quinase 3 beta/genética , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Mutação de Sentido Incorreto , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Polimorfismo de Nucleotídeo Único , Superóxido Dismutase/genética , Adulto JovemRESUMO
Technological advancement has increasingly exposed humans to magnetic fields (MFs). However, more insights are necessary into the potential toxicity of MF exposure as a result of genetic variations related to oxidative metabolism. Therefore, the following study has assessed an in vitro cytotoxic effect of static magnetic field (SMF) (5 mT) on cells with Val16Ala polymorphism (AA, VA, and VV) in the manganese superoxide dismutase gene. Homozygous Val16Ala-superoxide dismutase 2 (SOD2) genotypes present oxidative imbalance that is associated with risk to several chronic degenerative diseases (VV produces less efficient and AA more efficient SOD2 enzyme). Blood samples from healthy adult subject carriers with different Val16Ala-SOD2 genotypes were obtained and exposed to MF at different times (0, 1, 3, 6 h). The cytotoxic effect as well as oxidative stress was evaluated after incubation of 24 h at 37 °C. In addition, apoptosis induction has been analyzed by flow cytometry as well as Bcl-2-associated X protein (BAX), B-cell lymphoma 2 (BCL-2), and caspases 8 and 3 gene expression. SMF cytotoxic effect has been observed in AA cells at all times of exposure, whereas AV cells presented higher mortality only after 6 h of exposure at SMF. Higher apoptosis induction has been observed in AA cells when compared to VV and AV cells. These results suggest a toxicogenetic SMF effect related to an imbalance in SOD2 activity.
Assuntos
Campos Magnéticos/efeitos adversos , Polimorfismo Genético , Superóxido Dismutase/genética , Apoptose , Células Cultivadas , Genótipo , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Oxirredução , Estresse Oxidativo/efeitos dos fármacosRESUMO
Stroke risk has been associated to the progression of carotid plaques due to high glucose levels and lipid accumulation, which are greatly associated to cerebral injury, brain oxidative stress, and apoptosis. The ALA16VAL-MnSOD gene single nucleotide polymorphism (SNP) has shown to modulate risk factors of several metabolic and vascular diseases, such as blood glucose (GLU) and lipid levels. However, the association of these factors in stroke patients has not been studied to date. Thus, we evaluated the influence of the Ala16Val-MnSOD SNP on lipid profile, GLU levels, oxidative and DNA damage of 44 patients in a late phase of stroke (>6months). The statistical analysis showed a greater proportion of VV carries in stroke patients. The results also indicated that stroke patients had higher cholesterol (CHO) and GLU levels when compared to healthy counterparts. Interestingly, V allele carriers with stroke showed higher levels of CHO and GLU when compared to AA stroke and healthy counterparts. Our findings suggest that oxidative stress markers are still increased even after 6 months of cerebral injury. Furthermore, we propose that the Ala16Val-MnSOD SNPs may contribute to hypercholesterolemia and higher GLU levels, increasing the risk to neurovascular events that may lead to stroke.
Assuntos
Predisposição Genética para Doença , Glucose/metabolismo , Hipercolesterolemia/genética , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/genética , Superóxido Dismutase/genética , Substituição de Aminoácidos , Estudos de Casos e Controles , HumanosRESUMO
The aim of the study was to investigate the effect of the oral administration of tucumã oil (Astrocaryum vulgare) on glucose and insulin levels, oxidative status, and pancreatic genotoxic parameters of alloxan-induced diabetic mice. The animals were divided into four groups (n = 6 each): control/water; control/tucumã oil; diabetic/water; diabetic/tucumã oil treated for 14 days with 5.0 mL kg-1 via oral gavage. Gas chromatograph characterization demonstrated that oleic/elaidic fatty acid is the most abundant component present in this oil, followed by palmitic and stearic fatty acids. Our results demonstrated an increase (p < 0.05) in water and food intake, blood glucose, thiobarbituric acid reactive species (TBARS) levels, damage index, and frequency of damage; conversely body weight, insulin levels, catalase (CAT) and superoxide dismutase (SOD) activities, and cell viability were decreased in the diabetic/water group compared to the control/water group. The treatment with tucumã oil prevented these alterations in the diabetic/tucumã oil group compared to the diabetic/water group, and restored these parameters near to the control/water group. In summary, our findings demonstrated that treatment with tucumã oil causes a hypoglycemic effect improving insulin levels and antioxidant/oxidant status, and has a protector effect against pancreatic damage induced by oxidative stress in alloxan-induced diabetic mice.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Ácidos Graxos/sangue , Hiperglicemia/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Aloxano/toxicidade , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Peso Corporal/efeitos dos fármacos , Cromatografia Gasosa , Diabetes Mellitus Experimental/induzido quimicamente , Ativação Enzimática/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Superóxido Dismutase/metabolismoRESUMO
Oxidized LDL (ox-LDL) is involved in the initiation and progression of atherosclerosis. Many factors can affect the LDL oxidation such as oxidative stress. The present study tested whether ox-LDL levels would be associated with apolipoprotein E (APOE), manganese superoxide dismutase (MnSOD) Ala16Val polymorphisms, and classic cardiovascular risk factors. ox-LDL levels were measured by thiobarbituric acid-reactive substances and both polymorphisms were determined by polymerase chain reaction/restriction fragment length polymorphism in a sample of 252 subjects (70 men, 182 women, mean age, 54-85 years). Subjects with ox-LDL >or=0.5 nmol/mg apoprotein were considered the high level group (HLG, N = 82) and subjects with ox-LDL <0.5 nmol/mg apoprotein were considered the expected level group (ELG, N = 170). Classic risk factors were also evaluated. The results showed that diabetes mellitus was more prevalent in HLG, whereas other cardiovascular risk factors were similar between groups. The APOE genotype frequencies did not differ between HLG and ELG subjects. However, AA genotype from MnSOD polymorphism was more frequent in ELG (chi(2) = 8.48; P = 0.014). AV and VV subjects from ELG present highest ox-LDL levels (OR = 3.61; CI95% = 1.42-9.17) than AA. Additional analysis did not find gene-gene interactions associated with ox-LDL levels. Multivariate analysis showed that diabetes and the MnSOD polymorphism were independent factors associated with higher ox-LDL levels in HLG. The results suggest that an important framework on modulation of the redox status influenced by genetic polymorphisms could affect the cardiovascular homeostasis.
Assuntos
Apolipoproteínas E/genética , Doenças Cardiovasculares/sangue , Lipoproteínas LDL/sangue , Polimorfismo Genético/genética , Superóxido Dismutase/genética , Idoso , Idoso de 80 Anos ou mais , Brasil , Doenças Cardiovasculares/genética , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Fatores de Risco , Substâncias Reativas com Ácido TiobarbitúricoRESUMO
Oxidative stress and brain inflammation are thought to contribute to the pathophysiology of cerebral injury in acute stroke, leading to apoptosis and cell death. Lipid accumulation may lead to progression of carotid plaques and inflammation, contributing to increased acute stroke risk. However, little is known about these events and markers in the late stroke (>6 months) and if dyslipidemia could contribute to disease's pathophysiology in a later phase. In this case-control study, we recruited patients in the late stroke phase (n=40) and health subjects (control group; n = 40). Dichlorodihydrofluorescein (DCFH), nitrite/nitrate (NOx), Tumor necrosis factor-alpha (TNF-α), Acetylcholinesterase (AChE), Caspase 8 (CASP 8), Caspase 3 (CASP 3) and Picogreen (PG) were measured in periphery blood samples. Furthermore, a correlation among all measured markers (DCFH, NOx, TNF-α, AChE, CASP 8, CASP 3 and PG) was realized. The marker levels were also compared to triglycerides (TG), total (CHO), LDL and HDL cholesterol levels and medications used. Statistical analyses showed that stroke patients presented an increase of DCFH, NOx, TNF-α and AChE levels when compared to control subjects. In addition, we observed that stroke patients had significantly higher CASP 8, CASP 3 and PG levels than control group. A significant correlation between TNF-α with CASP 8 (r = 0.4) and CASP 3 (r = 0.4) levels was observed, but not with oxidative/nitrosative markers. Moreover, we observed that stroke patients with dyslipidemia had significantly higher TNF-α, CASP 8 and CASP 3 levels than stroke without dyslipidemia and control groups. Our findings suggest that oxidative and inflammatory markers may be still increased and lead to caspase activation and DNA damage even after 6 months to cerebral injury. Furthermore, it is plausible to propose that dyslipidemia may contribute to worsen proinflammatory state in a later phase of stroke and an increased risk to new neurovascular events.