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1.
Free Radic Res ; 54(7): 477-496, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32842814

RESUMO

Smokeless tobacco (SLT) or chewing tobacco has been a highly addictive practice in India across ages, posing major threat to the systemic health and possibly neurodegeneration. Earlier studies showed components of SLT could be harmful to neuronal health. However, mechanism of SLT in neurodegeneration remained unexplored. This study investigated the detrimental role of SLT on differentiated neuronal cell lines, PC12 and SH-SY5Y by using graded doses of water soluble lyophilised SLT. Reduced cell viability, compromised mitochondrial structure and functions were observed when neuronal cell lines were treated with SLT (6 mg/mL) for 24 h. There was reduction of oxidative phosphorylation and aerobic glycolysis as determined by diminution of ATP production (2.5X) and basal respiration (1.9X). Mitochondrial membrane potential was dropped by 3.5 times. Bid, a pro-apoptotic Bcl-2 family protein, has imperative role in regulating mitochondrial outer membrane permeabilization and subsequent cytochrome c release leading to apoptosis. This article for the first time indicated the involvement of Bid in SLT mediated neurotoxicity and possibly neurodegeneration. SLT treatment enhanced expression of cleaved-Bid in time dependent manner. The involvement of Bid was further confirmed by using Bid specific shRNA which reversed the effects of SLT and conferred significant protection from apoptosis up to 72 h. Thus, our results clearly indicated that SLT induced neuronal cell death occurred via production of ROS, alteration of mitochondrial morphology, membrane potential and oxidative phosphorylation, inactivation of survival pathway and activation of apoptotic markers mediated by Bid. Therefore, Bid could be a potential future therapeutic target for SLT induced neurodegeneration.


Assuntos
Neurônios/patologia , Tabaco sem Fumaça/toxicidade , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Linhagem Celular Tumoral , Citocromos c/metabolismo , Dano ao DNA , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fosforilação Oxidativa , Células PC12 , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Proteína Supressora de Tumor p53/metabolismo
2.
J Oleo Sci ; 69(8): 941-950, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32759552

RESUMO

This study reports the biological activity of essential oils from fertility tree and horseradish tree leaves, and the mechanisms by which these oils promote insecticidal activity using Drosophila melanogaster as a model organism. Adult D. melanogaster were exposed to these essential oils at a final concentration of 10 µL/g for 24 hours. The exposure of flies to the essential oil resulted in significant decrease in their survival and fecundity. In addition, the essential oils produced significant reduction in acetylcholinesterase activity and induced oxidative stress in the flies as evidenced by an increase in reactive oxygen species, thiol and thiobarbituric reactive substance levels, as well as catalase activity. The essential oils were also characterized by gas chromatography coupled with mass spectrometry. Constituents such as terpenoids, Bis (2-ethylhexyl) phthalate, benzeneacetaldehyde, phytol, octadecane, 9,12-octadecadienoic acid (Z,Z)- methyl ester, heneicosane, eicosane and others were characterized. Therefore, our results point out to the potential application of fertility tree and horseradish tree leaf essential oils as natural alternatives to synthetic insecticides in agricultural and pest control practices, especially against dipterans.


Assuntos
Acetilcolinesterase/metabolismo , Bignoniaceae/química , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/metabolismo , Inseticidas , Moringa oleifera/química , Óleos Voláteis/isolamento & purificação , Óleos Voláteis/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Folhas de Planta/química , Animais , Relação Dose-Resposta a Droga , Óleos Voláteis/química , Ácidos Ftálicos/análise , Espécies Reativas de Oxigênio/metabolismo , Terpenos/análise , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fatores de Tempo
3.
J Vis Exp ; (159)2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32478759

RESUMO

Despite its limited analytical specificity and ruggedness, the thiobarbituric acid reactive substances (TBARS) assay has been widely used as a generic metric of lipid peroxidation in biological fluids. It is often considered a good indicator of the levels of oxidative stress within a biological sample, provided that the sample has been properly handled and stored. The assay involves the reaction of lipid peroxidation products, primarily malondialdehyde (MDA), with thiobarbituric acid (TBA), which leads to the formation of MDA-TBA2 adducts called TBARS. TBARS yields a red-pink color that can be measured spectrophotometrically at 532 nm. The TBARS assay is performed under acidic conditions (pH = 4) and at 95 °C. Pure MDA is unstable, but these conditions allow the release of MDA from MDA bis(dimethyl acetal), which is used as the analytical standard in this method. The TBARS assay is a straightforward method that can be completed in about 2 h. Preparation of assay reagents are described in detail here. Budget-conscious researchers can use these reagents for multiple experiments at a low cost rather than buying an expensive TBARS assay kit that only permits construction of a single standard curve (and thus can only be used for one experiment). The applicability of this TBARS assay is shown in human serum, low density lipoproteins, and cell lysates. The assay is consistent and reproducible, and limits of detection of 1.1 µM can be reached. Recommendations for the use and interpretation of the spectrophotometric TBARS assay are provided.


Assuntos
Bioensaio/métodos , Estresse Oxidativo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Colorimetria , Células Hep G2 , Humanos , Limite de Detecção , Peroxidação de Lipídeos , Lipoproteínas LDL/metabolismo , Malondialdeído/sangue , Oxirredução , Padrões de Referência , Reprodutibilidade dos Testes
4.
Life Sci ; 254: 117787, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32417372

RESUMO

AIMS: To evaluate the effects of esculin treatment on P2X7 receptor and mitochondrial dysfunction in the renal cortex of diabetic rats. MAIN METHODS: Male Wistar rats, 7 weeks old, were unilaterally nephrectomized. Part of these animals were induced to diabetes using streptozotocin (60 mg/kg). Diabetes was confirmed 48 h after induction, with blood glucose levels ≥200 mg/dL. Part of control and diabetic animals were selected to receive daily doses of esculin (50 mg/kg), during 8 weeks. The animals were placed in metabolic cages at the eighth week of protocol for 24 h urine collection and a small aliquot of blood was collected for biochemical analysis. After this procedure, the animals were euthanized and the remaining kidney was stored for histopathological analysis, Western blotting and mitochondrial high-resolution respirometry. KEY FINDINGS: Although esculin did not change metabolic parameters, renal biochemical function, neither TBARS in DM rats, esculin reduced P2X7 levels in these animals and restored mitochondrial function via glycolysis substrates and ß-oxidation. Besides, at the histological analysis, we observed that esculin reduced inflammatory infiltrates and collagen IV deposits as compared to diabetic group. SIGNIFICANCE: Esculin attenuated the development of renal injuries caused by hyperglycemia, proinflammatory and oxidative mechanisms mediated by P2X7 receptor, as seen by histological findings and improved mitochondrial function in diabetic animals. This suggests that esculin could be used as an adjuvant therapy to prevent the diabetic nephropathy.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Esculina/farmacologia , Córtex Renal/metabolismo , Mitocôndrias/metabolismo , Receptores Purinérgicos P2X7/metabolismo , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/patologia , Colágenos Fibrilares/metabolismo , Glicólise/efeitos dos fármacos , Inflamação/prevenção & controle , Córtex Renal/patologia , Masculino , Oxirredução/efeitos dos fármacos , Ratos , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
5.
Am J Physiol Regul Integr Comp Physiol ; 318(6): R1103-R1115, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32401626

RESUMO

This study aimed to investigate the effects of a short-term (36 h) fasting period combined with an acute bout of exercise on markers of immune function and inflammation in healthy human subjects. Fourteen moderately trained male subjects (aged 19-39 yr) participated in a 36-h fasting trial (FA-T), followed by an acute bout of moderate exercise (60% V̇o2max). After 1 wk, the same subjects, as their own control, participated in a nonfasting trial (NFA-T) in which they performed an exercise trial of the same duration and intensity. Blood samples were taken before, immediately after, and 1 h after each exercise bout and analyzed for several immunological and metabolic markers. At baseline, fasting subjects showed lower levels of T cell apoptosis, lymphocyte-proliferative responses, IL-6, monocyte chemoattractant protein-1 (MCP-1), insulin, and leptin (P < 0.05) as well as higher levels of neutrophil oxidative burst and thiobarbituric acid reactive substances (TBARS) than those in the NFA-T (P < 0.05). After the exercise protocol, fasted subjects revealed higher T cell apoptosis, neutrophil oxidative burst, TBARS, TNFα, and MCP-1 levels as well as lower levels of lymphocyte-proliferative response, IL-6, insulin, and leptin than those in the NFA-T (P < 0.05). Short-term fasting aggravates perturbations in markers of immune function, and inflammation was induced by an acute moderate-intensity exercise protocol.


Assuntos
Exercício Físico/fisiologia , Jejum/sangue , Inflamação/sangue , Adulto , Apoptose/fisiologia , Biomarcadores/sangue , Quimiocina CCL2/sangue , Voluntários Saudáveis , Humanos , Insulina/sangue , Interleucina-6/sangue , Leptina/sangue , Masculino , Estresse Oxidativo/fisiologia , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fator de Necrose Tumoral alfa/sangue , Adulto Jovem
6.
Am J Physiol Renal Physiol ; 318(5): F1199-F1209, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32249612

RESUMO

Lithium is widely used in psychiatry as the golden standard for more than 60 yr due to its effectiveness. However, its adverse effect has been limiting its long-term use in clinic. About 40% of patients taking lithium develop nephrogenic diabetes insipidus (NDI). Lithium can also induce proliferation of collecting duct cells, leading to microcyst formation in the kidney. Lithium was considered an autophagy inducer that might contribute to the therapeutic benefit of neuropsychiatric disorders. Thus, we hypothesized that autophagy may play a role in lithium-induced kidney nephrotoxicity. To address our hypothesis, we fed mice with a lithium-containing diet with chloroquine (CQ), an autophagy inhibitor, concurrently. Lithium-treated mice presented enhanced autophagy activity in the kidney cortex and medulla. CQ treatment significantly ameliorated lithium-induced polyuria, polydipsia, natriuresis, and kaliuresis accompanied with attenuated downregulation of aquaporin-2 and Na+-K+-2Cl- cotransporter protein. The protective effect of CQ on aquaporin-2 protein abundance was confirmed in cultured cortical collecting duct cells. In addition, we found that lithium-induced proliferation of collecting duct cells was also suppressed by CQ as detected by proliferating cell nuclear antigen staining. Moreover, both phosphorylated mammalian target of rapamycin and ß-catenin expression, which have been reported to be increased by lithium and associated with cell proliferation, were reduced by CQ. Taken together, our study demonstrated that CQ protected against lithium-induced NDI and collecting duct cell proliferation possibly through inhibiting autophagy.


Assuntos
Proliferação de Células/efeitos dos fármacos , Cloroquina/farmacologia , Diabetes Insípido Nefrogênico/prevenção & controle , Túbulos Renais Coletores/efeitos dos fármacos , Cloreto de Lítio , Animais , Aquaporina 2/genética , Aquaporina 2/metabolismo , Autofagia/efeitos dos fármacos , Linhagem Celular , Diabetes Insípido Nefrogênico/induzido quimicamente , Diabetes Insípido Nefrogênico/metabolismo , Diabetes Insípido Nefrogênico/patologia , Dinoprostona/urina , Modelos Animais de Doenças , Túbulos Renais Coletores/metabolismo , Túbulos Renais Coletores/patologia , Masculino , Camundongos da Linhagem 129 , Natriurese/efeitos dos fármacos , Fosforilação , Poliúria/induzido quimicamente , Poliúria/metabolismo , Poliúria/patologia , Poliúria/prevenção & controle , Membro 1 da Família 12 de Carreador de Soluto/genética , Membro 1 da Família 12 de Carreador de Soluto/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , beta Catenina/metabolismo
7.
Spine (Phila Pa 1976) ; 45(9): E515-E524, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32282654

RESUMO

MINI: In this study, respiratory function at the time of extubation can be useful optimal clinical guidelines for weaning and extubation attempts in patients with acute cervical spinal cord injury. Serum thiobarbituric acid-reactive substances level at admission can be a useful predictor for severity in acute cervical patients with spinal cord injury. STUDY DESIGN: Patients who had suffered from acute blunt cervical spinal cord injury (SCI) and admitted our hospital within 24 hours after injury were included in the study. OBJECTIVE: We compared the respiratory function and serum reactive oxidative stress (ROS) after acute cervical SCI, and tried to find out the valuable predictors of weaning in patients with acute cervical SCI. SUMMARY OF BACKGROUND DATA: Ventilation impairment is a major complication of acute cervical SCI. Evidence of oxygen radical formation in secondary injury from animal SCI models demonstrates an immediate postinjury increase in ROS production after SCI. We hypothesize that the serum ROS is associated with the severity of patients with acute cervical SCI. METHODS: Thirty-eight adult patients who had acute cervical SCI and 58 healthy volunteers were enrolled. Respiratory function at admission, at the time of extubation and at 48 hours after extubation, serum oxidative stress, Injury Severity Score and Japanese Orthopaedic Association score at admission were compared. RESULTS: The most notable predictor of mechanical ventilation more than 48 hours was serum thiobarbituric acid-reactive substances (TBARS) level at admission (P = 0.027), and the cut-off value of serum TBARS level was 731.7 µmol/L (sensitivity 87.5% and specificity 78.9%). For the reventilation ≤5 days, the notable predictors were respiratory function at the time of extubation (maximal inspiratory pressure, P = 0.040; maximal expiratory pressure, P = 0.020; and tidal volume, P = 0.036) and serum TBARS level at admission (P = 0.013), the cut-off value of serum TBARS level at admission was 762.3 µmol/L (sensitivity 100% and specificity 90.0%). CONCLUSION: In this study, respiratory function (maximal inspiratory pressure, maximal expiratory pressure, and tidal volume) at the time of extubation can be useful optimal clinical guidelines for weaning and extubation attempts in patients with acute cervical SCI. Serum TBARS level at admission can be a useful predictor for severity in acute cervical SCI patients. LEVEL OF EVIDENCE: 3.


Assuntos
Extubação/tendências , Escala de Gravidade do Ferimento , Respiração Artificial/tendências , Mecânica Respiratória/fisiologia , Traumatismos da Medula Espinal/terapia , Adulto , Extubação/métodos , Vértebras Cervicais/lesões , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Lesões do Pescoço/sangue , Lesões do Pescoço/diagnóstico , Lesões do Pescoço/terapia , Estudos Prospectivos , Respiração Artificial/métodos , Traumatismos da Medula Espinal/sangue , Traumatismos da Medula Espinal/diagnóstico , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
8.
Ecotoxicol Environ Saf ; 194: 110381, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32145529

RESUMO

Combined with sediment pollutant analysis, the gastropod Cipangopaludina cahayensis was chosen as an indicator organism to evaluate the environmental behavior of trace metals and the aquatic ecological risk that they present in a backwater area of Xian'nv Lake. Based on hydrological characteristics, 24 sampling sites representing the main stream (MS), tributaries (TR), lake area (LA) and lake tributaries (LT) were collected. The results revealed that cadmium (Cd) was the main pollutant and that it significantly accumulated in sediments of the research area. Based on the pollutant concentrations, the degree of Cd pollution was ranked in the following order: LA > MS > TR > LT. Several intersections between the rivers and Xian'nv Lake, including LA1, LA7 and LA 10, were observed to have higher Cd deposition. There was a significant difference in the spatial distribution of pollutants, which resulted in a higher accumulation of trace metals in the backwater area and its tributary. The Cd content in the visceral sac of C. cahayensis was positively correlated with the concentration of heavy metals in the sediment. The response of multiple antioxidant biomarkers, including superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST), as well as the glutathione (GSH) content and the level of by-products of lipid peroxidation (TBARS), in C. cahayensis revealed a potential relationship to the environmental behavior of the pollutants. By combining the different biomarkers responses, the integrated biomarker response index (IBR) corresponded well with the pollution distribution characteristics in different areas.


Assuntos
Cádmio/análise , Biomarcadores Ambientais/efeitos dos fármacos , Monitoramento Ambiental/métodos , Gastrópodes/efeitos dos fármacos , Lagos/química , Oligoelementos/análise , Poluentes Químicos da Água/análise , Animais , Cádmio/toxicidade , Catalase/metabolismo , China , Gastrópodes/metabolismo , Sedimentos Geológicos/química , Glutationa/metabolismo , Rios/química , Análise Espacial , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Oligoelementos/toxicidade , Poluentes Químicos da Água/toxicidade
9.
Ann Hematol ; 99(5): 937-945, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32166377

RESUMO

Hydroxyurea (HU) is used as a therapy in sickle cell anemia (SCA). Many studies have established that HU improves patient quality of life by reducing symptoms. However, the effect of HU on erythrocytes is not well-described. We evaluated several parameters related to oxidative stress and total lipid content of erythrocytes in patients with SCA. The patient cohort consisted of 7 SCA patients treated with HU, 17 untreated SCA patients, and 15 healthy subjects. Erythrocytes from patients with SCA displayed increased oxidative stress relative to the control group, including higher thiobarbituric acid reactive substances (TBARS), Fe3+ content, and osmotic fragility, and decreased total cholesterol. We observed that treatment of SCA patients with HU increased Fe3+ content and activity of glutathione peroxidase, and decreased glutathione reductase activity, glutathione levels, total cholesterol, and phospholipid content comaperaded to patients untreated with HU. Thus, HU alters biochemical characteristics of erythrocytes; future studies will determine whether they are beneficial or not.


Assuntos
Anemia Falciforme , Eritrócitos Anormais/metabolismo , Hidroxiureia/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Adulto , Anemia Falciforme/sangue , Anemia Falciforme/tratamento farmacológico , Colesterol/sangue , Feminino , Humanos , Masculino , Fragilidade Osmótica/efeitos dos fármacos , Fosfolipídeos/sangue , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
10.
Ecotoxicol Environ Saf ; 193: 110341, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32092582

RESUMO

An in-situ experiment was performed to study metabolic responses of the freshwater mussel Diplodon chilensis to water contaminated by leachates from an open dump and cattle activity, in order to analyze both the effects of those contaminants on aquatic environments and the potential use of a native bivalve to evaluate the effects of anthropic influence and eutrophication. Bivalves from a reference site were cage-transplanted to a control site (site A) and to a temporal water pond (site B) over 30 and 60 periods. Water quality analyses revealed that the site B was affected by anthropogenic influence. Mussel's hemocytes from site B showed 50% lower reactive oxygen species production and 130% higher lysosomal membrane stability in the site B mussels. In addition, no oxidative stress was evident in gills, despite the elevated copper and iron concentrations recorded in the site B water samples (CuB = 0.3350 ± 0.0636 mg. L-1vs. CuA = 0.0045 ± 0.0007 mg. L-1; FeB = 3.8650 ± 0.4031 mg. L-1vs. FeA = 0.0365 ± 0.0049 mg. L-1). In contrast, the adductor muscle accumulated more Fe (~10-20-fold) than the gills and showed signs of oxidative stress, e.g. superoxide dismutase activity and TBARS levels were increased by 10% were 34%, respectively, in the site B compared with the site A after 60 days of exposure. Additionally, the adductor muscle showed signs of anaerobic metabolism activation. Cu is accumulated in gills from both sites' individuals, at 60 days, in concordance with the increase in the activity of the cu-containing enzyme cytochrome-c-oxidase. There was a reduction in the overall condition and digestive gland index in bivalves exposed at site B, associated with diminished levels of lipid and protein contents. Metal-pollution and eutrophication affects D. chilensis metabolism and is associated to tissue-specific exposure, anaerobic metabolism and general energetic condition depletion.


Assuntos
Bivalves/efeitos dos fármacos , Eutrofização , Metais Pesados/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Bivalves/enzimologia , Bivalves/metabolismo , Bovinos , Cobre/metabolismo , Água Doce , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Hemócitos/efeitos dos fármacos , Hemócitos/metabolismo , Metais Pesados/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Poluentes Químicos da Água/metabolismo , Qualidade da Água
11.
Oxid Med Cell Longev ; 2020: 6361703, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32104536

RESUMO

Taken into consideration that oxidative stress response after preconditioning with phosphodiesterase inhibitors (PDEIs) and moderate physical activity has still not been clarified, the aim of this study was to assess the effects of PDEIs alone or in combination with physical activity, on systemic redox status. The study was carried out on 96 male Wistar albino rats classified into two groups. The first group included animals exposed only to pharmacological preconditioning (PreC) maneuver (sedentary control (CTRL, 1 ml/day saline, n = 12), nicardipine (6 mg/kg/day of NIC, n = 12), vinpocetine (10 mg/kg/day of VIN, n = 12), and nimodipine (NIM 10 mg/kg/day of, n = 12). The second included animals exposed to preconditioning with moderate-intensity training (MIT) on treadmill for 8 weeks. After 5 weeks from the start of training, the animals were divided into four subgroups depending on the medication to be used for pharmacological PreC: moderate-intensity training (MIT+ 1 ml/day saline, n = 12), nicardipine (MIT+ 6 mg/kg/day of NIC, n = 12), vinpocetine (MIT+ 10 mg/kg/day of VIN, n = 12), and nimodipine (MIT+ 10 mg/kg/day of NIM, n = 12). After three weeks of pharmacological preconditioning, the animals were sacrificed. The following oxidative stress parameters were measured spectrophotometrically: nitrites (NO2 -), superoxide anion radical (O2 -), hydrogen peroxide (H2O2), index of lipid peroxidation (TBARS), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH). Our results showed that PDE1 and MIT preconditioning decreased the release of prooxidants and improved the activity of antioxidant enzymes thus preventing systemic oxidative stress.


Assuntos
Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Inibidores de Fosfodiesterase/farmacologia , Condicionamento Físico Animal/fisiologia , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Glutationa/metabolismo , Masculino , Nicardipino/farmacologia , Nimodipina/farmacologia , Oxirredução/efeitos dos fármacos , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Superóxidos/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Alcaloides de Vinca/farmacologia
12.
Artigo em Inglês | MEDLINE | ID: mdl-32041360

RESUMO

Melatonin plays an essential role in the regulation of bone growth. The actions that melatonin exerts on odontoblasts may be similar to its action on osteoblasts. This research aimed to evaluate the pulp response to melatonin used for direct pulp capping to evaluate the antioxidant effect of melatonin administered orally and its influence on dental pulp. Direct pulp capping was performed on the upper molars of Sprague Dawley rats using melatonin or Mineral Trioxide Aggregate (MTA). The study groups were: MTA; Melatonin; MTA + Melatonin administered orally; and Melatonin + Melatonin administered orally. In the latter two groups, the animals drank water dosed with melatonin ad libitum (10 mg/100 mL). After 30 days, the animals were sacrificed, and 5 ml of blood, the kidneys, and the liver were extracted in order to evaluate oxidative stress using thiobarbituric acid reactive substances testing (TBARS). Fragments of the maxilla containing the study molars were prepared for histological evaluation. The degree of pulp inflammation and pulp necrosis, the presence of reparative dentin and dentin bridging the pulp chamber, the presence and regularity of the odontoblastic layer, and the presence of pulp fibrosis were evaluated. No significant differences were found between the four study groups for any of the studied histological variables. The oral administration of melatonin did not modify the local effects of MTA or melatonin on dental pulp, or reduce basal-level oxidative stress. The effect of melatonin on pulp is similar to that of MTA and may be used as an agent for direct pulp capping.


Assuntos
Compostos de Alumínio/farmacologia , Antioxidantes/farmacologia , Compostos de Cálcio/farmacologia , Melatonina/farmacologia , Óxidos/farmacologia , Agentes de Capeamento da Polpa Dentária e Pulpectomia/farmacologia , Silicatos/farmacologia , Animais , Dentina Secundária/efeitos dos fármacos , Combinação de Medicamentos , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Dente Molar/efeitos dos fármacos , Ratos Sprague-Dawley , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
13.
Am J Physiol Renal Physiol ; 318(2): F509-F517, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31904280

RESUMO

Endothelial dysfunction, characterized by reduced bioavailability of nitric oxide and increased oxidative stress, is a hallmark characteristic in diabetes and diabetic nephropathy (DN). High levels of asymmetric dimethylarginine (ADMA) are observed in several diseases including DN and are a strong prognostic marker for cardiovascular events in patients with diabetes and end-stage renal disease. ADMA, an endogenous endothelial nitric oxide synthase (NOS3) inhibitor, is selectively metabolized by dimethylarginine dimethylaminohydrolase (DDAH). Low DDAH levels have been associated with cardiac and renal dysfunction, but its effects on DN are unknown. We hypothesized that enhanced renal DDAH-1 expression would improve DN by reducing ADMA and restoring NOS3 levels. DBA/2J mice injected with multiple low doses of vehicle or streptozotocin were subsequently injected intrarenally with adenovirus expressing DDAH-1 (Ad-h-DDAH-1) or vector control [Ad-green fluorescent protein (GFP)], and mice were followed for 6 wk. Diabetes was associated with increased kidney ADMA and reduced kidney DDAH activity and DDAH-1 expression but had no effect on kidney DDAH-2 expression. Ad-GFP-treated diabetic mice showed significant increases in albuminuria, histological changes, glomerular macrophage recruitment, inflammatory cytokine and fibrotic markers, kidney ADMA levels, and urinary thiobarbituric acid reactive substances excretion as an indicator of oxidative stress, along with a significant reduction in kidney DDAH activity and kidney NOS3 mRNA compared with normal mice. In contrast, Ad-h-DDAH-1 treatment of diabetic mice reversed these effects. These data indicate, for the first time, that DDAH-1 mediates renal tissue protection in DN via the ADMA-NOS3-interaction. Enhanced renal DDAH-1 activity could be a novel therapeutic tool for treating patients with diabetes.


Assuntos
Adenoviridae/genética , Amidoidrolases/biossíntese , Arginina/análogos & derivados , Diabetes Mellitus Experimental/terapia , Nefropatias Diabéticas/prevenção & controle , Terapia Genética , Vetores Genéticos , Rim/enzimologia , Albuminúria/enzimologia , Albuminúria/genética , Albuminúria/prevenção & controle , Amidoidrolases/genética , Animais , Arginina/metabolismo , Citocinas/genética , Citocinas/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/enzimologia , Diabetes Mellitus Experimental/genética , Nefropatias Diabéticas/enzimologia , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/genética , Fibrose , Mediadores da Inflamação/metabolismo , Rim/patologia , Masculino , Camundongos Endogâmicos DBA , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Estresse Oxidativo , Transdução de Sinais , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
14.
Psychiatry Res ; 284: 112782, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31955054

RESUMO

INTRODUCTION: This study investigates the alteration of the inflammatory/oxidative pathway in patients with borderline personality disorder (BPD) and its relationship with clinical features of the disorder. METHODS: 49 BPD patients and 33 healthy control subjects were studied. Plasma levels of TBARS, nitrites, and the antioxidant enzymes CAT, GPx and SOD were measured. In addition, peripheral blood mononuclear cells were obtained to investigate levels of intracellular components of the inflammatory/oxidative pathway including the IκBα, NFκB, iNOS, COX2, Keap1, NQO1, and HO1. Western Blot and ELISA were used to measure protein expression. Patients were assessed for different clinical dimensions of BPD with scales for depression, anxiety, impulsivity and functioning. RESULTS: A significant decrease of IκBα levels and a significant increase of inflammatory factors, including NFκB, COX2 and iNOS levels were found in patients. On the other hand, a significant decrease was observed for all antioxidant enzymes in patients with BPD, except for HO1. The inflammatory factor NFκB showed a significant positive correlation with impulsivity scores. CONCLUSIONS: Patients with BPD presented an increased activation of several components of the inflammatory pathways, as well as an inhibition of the antioxidant path. These alterations appear partially correlated with the impulsivity scores in these patients.


Assuntos
Antioxidantes/metabolismo , Transtorno da Personalidade Borderline/sangue , Transtorno da Personalidade Borderline/fisiopatologia , Mediadores da Inflamação/sangue , Adulto , Biomarcadores/sangue , Transtorno da Personalidade Borderline/psicologia , Feminino , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Fator 2 Relacionado a NF-E2/sangue , Óxido Nítrico Sintase Tipo II/sangue , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
15.
Biosci Biotechnol Biochem ; 84(3): 621-632, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31762379

RESUMO

The antioxidant activity of Petasites japonicus flower buds cultivated in Tokushima, Japan, was examined in vitro and in vivo. The flower bud extracts were assayed using either oxygen radical absorbance capacity or 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity. Antioxidants in the 80% ethanol extract were investigated using online high-performance liquid chromatography-DPPH and were identified as caffeic acid, 3-O-caffeoylquinic acid, fukinolic acid, 3,4-di-O-caffeoylquinic acid, 3,5-di-O-caffeoylquinic acid, and 4,5-di-O-caffeoylquinic acid using liquid chromatography-mass spectrometry. Fukinolic acid was the most active compound based on its activity and abundance. Administering the extracts orally to ICR mice prior to iron injection significantly suppressed plasma thiobarbituric acid reactive substance (TBARS) production. Moreover, TBARS and triglyceride concentrations in the plasma of C57BL/6 mice fed with a high fat diet were also significantly decreased by the extract. The results suggest that antioxidative compounds in P. japonicus can be used in the management of oxidative stress.


Assuntos
Antioxidantes/farmacologia , Flores/química , Petasites/química , Extratos Vegetais/farmacologia , Animais , Cromatografia Líquida de Alta Pressão/métodos , Técnicas In Vitro , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Estresse Oxidativo/efeitos dos fármacos , Espectrometria de Massas em Tandem , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
16.
Food Chem Toxicol ; 135: 111038, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31825855

RESUMO

The aim of the study was to evaluate the potential protective role of sildenafil and tadalafil in contrast-induced nephropathy (CIN) by modulating oxidative stress. Thirty Wistar male rats were equally assigned into five groups: sham, CIN, CIN + sildenafil (10 mg/kg bw/day), CIN + tadalafil (5 mg/kg bw/day) and CIN + N-Acetyl Cysteine (NAC) (100 mg/kg bw/day) as a positive control. CIN was induced by 12 h dehydration and administration of indomethacin (10 mg/kg bw), N-ω- nitro-L-arginine methyl ester (10 mg/kg bw), and iopromide (3 g/kg bw iodine). Blood was drawn prior to and 24 h after CIN induction for evaluating renal function and oxidative stress. In the CIN group, total antioxidant capacity (TAC), reduced glutathione (GSH) and catalase (CAT) levels were significantly decreased; and protein carbonyl (PROTC) and thiobarbituric reactive species (TBARS) were significantly increased compared to the sham group. Pre- Sildenafil and tadalafil pre-treatment reduced CIN risk and reversed oxidative stress almost to the sham group levels. These results suggest that PDE5Is can be good candidates for preventing CIN based on their ability to modulate the oxidant/antioxidant balance.


Assuntos
Antioxidantes/metabolismo , Meios de Contraste/efeitos adversos , Nefropatias/induzido quimicamente , Nefropatias/prevenção & controle , Oxidantes/metabolismo , Inibidores da Fosfodiesterase 5/farmacologia , Citrato de Sildenafila/farmacologia , Tadalafila/farmacologia , Acetilcisteína/administração & dosagem , Animais , Catalase/metabolismo , Modelos Animais de Doenças , Glutationa/metabolismo , Nefropatias/enzimologia , Nefropatias/metabolismo , Masculino , Camundongos , Estresse Oxidativo , Ratos , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
17.
J Strength Cond Res ; 34(1): 235-248, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30113919

RESUMO

Nunes, RFH, Cidral-Filho, FJ, Flores, LJF, Nakamura, FY, Rodriguez, HFM, Bobinski, F, De Sousa, A, Petronilho, F, Danielski, LG, Martins, MM, Martins, DF, and Guglielmo, LGA. Effects of far-infrared emitting ceramic materials on recovery during 2-week preseason of elite futsal players. J Strength Cond Res 34(1): 235-248, 2020-We investigated the effects of far-infrared emitting ceramic materials (cFIR) during overnight sleep on neuromuscular, biochemical and perceptual markers in futsal players. Twenty athletes performed a 2-week preseason training program and during sleep wore bioceramic (BIO; n = 10) or placebo pants (PL; n = 10). Performance (countermovement jump [CMJ]; squat jump [SJ]; sprints 5, 10, and 15-m) and biochemical markers (tumor necrosis factor alpha-TNF-α, interleukin 10-IL-10, thiobarbituric acid-reactive species [TBARS], carbonyl, superoxide dismutase [SOD], catalase [CAT]) were obtained at baseline and after the 1st and 2nd week of training. Delayed-onset muscle soreness (DOMS) and training strain were monitored throughout. Changes in ΔCMJ and ΔSJ were possibly (60/36/4 [week-1]) and likely (76/22/2 [week-2]) higher in BIO. Both groups were faster in 5-m sprint in week 2 compared with baseline (p = 0.015), furthermore, BIO was likely faster in 10-m sprint (3/25/72 [week 1]). Significant group × time interaction in %ΔTNF-α were observed (p = 0.024 [week-1]; p = 0.021 [week-2]) with values possibly (53/44/3 [week 1]) and likely (80/19/1 [week 2]) higher in BIO. The %ΔIL-10 decreased across weeks compared with baseline (p = 0.019 [week-1]; p = 0.026 [week-2]), showing values likely higher in BIO (81/16/3 [week-1]; 80/17/3 [week-2]). Significant weekly increases in %ΔTBARS (p = 0.001 [week-1]; p = 0.011 [week-2]) and %ΔCarbonyl (p = 0.002 [week-1]; p < 0.001 [week-2]) were observed compared with baseline, showing likely (91/5/4 [week-1]) and possibly (68/30/2 [week-2]) higher changes in BIO. Significant weekly decreases in %ΔSOD were observed compared with baseline (p = 0.046 [week 1]; p = 0.011 [week-2]), and between week 2 and week 1 (p = 0.021), in addition to significant decreases in %ΔCAT compared with baseline (p = 0.070 [week 1]; p = 0.012 [week 2]). Training strain (p = 0.021; very -likely [0/2/98]; week 1) and DOMS was lower in BIO (likely; 7 sessions) with differences over time (p = 0.001). The results suggest that the daily use of cFIR clothing could facilitate recovery, especially on perceptual markers during the early phases of an intensive training period.


Assuntos
Desempenho Atlético/fisiologia , Raios Infravermelhos/uso terapêutico , Condicionamento Físico Humano/fisiologia , Futebol/fisiologia , Adulto , Biomarcadores/sangue , Catalase/sangue , Cerâmica , Vestuário , Método Duplo-Cego , Teste de Esforço , Humanos , Interleucina-10/sangue , Movimento , Força Muscular/fisiologia , Músculo Esquelético/fisiopatologia , Mialgia/etiologia , Mialgia/terapia , Condicionamento Físico Humano/efeitos adversos , Recuperação de Função Fisiológica , Corrida , Sono , Superóxido Dismutase/sangue , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fator de Necrose Tumoral alfa/sangue , Adulto Jovem
18.
Ecotoxicol Environ Saf ; 190: 110071, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31841896

RESUMO

Aquatic environments are affected by the use of pesticides in agricultural areas near rivers. To assess the impact of pesticide residues on affected environments Danio rerio (zebrafish) embryos have become an alternative model for biomonitoring studies. In the present study, zebrafish embryos were used as bioindicator of water quality in the Vacacaí river, located in the city of Santa Maria, southern Brazil. We hypothesized that it would be possible to observe changes in the biomarkers tested in the embryos. Exposures were performed over a total of eight months during the year 2018 using water collected in a river located near agricultural areas. Twenty-four pesticides were found in river water samples. The most frequently found were atrazine, quinclorac and clomazone. During exposure (96 h) spontaneous movement, the heart rate and hatching rate were evaluated. After the exposure time the embryos were euthanized for biochemical assays. We analyzed biomarkers such as thiobarbituric acid reactive substance (TBARS), acetylcholinesterase (AChE), glutathione S-transferase (GST) and catalase (CAT). We observed increases in GST and TBARS, especially during periods of major water contamination such as January, February, October, and November. Pesticides can affect the development of native species that reproduce during periods of high agricultural production. These results demonstrate the potential use of biochemical parameters combined with developmental and behavioral analyses in zebrafish embryos for biomonitoring studies.


Assuntos
Praguicidas/análise , Rios/química , Poluentes Químicos da Água/análise , Acetilcolinesterase/metabolismo , Agricultura , Animais , Biomarcadores/metabolismo , Brasil , Catalase/metabolismo , Embrião não Mamífero/fisiologia , Glutationa Transferase/metabolismo , Frequência Cardíaca , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Peixe-Zebra/embriologia , Peixe-Zebra/fisiologia
19.
Int J Nanomedicine ; 14: 8943-8959, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819411

RESUMO

Objective: The study was designed to investigate the therapeutic potential of lactobionic acid (LA) conjugated quercetin (Q) loaded organically modified silica nanoparticles (LA-Q-ORMOSIL) with bulk quercetin to mitigate cyclophosphamide (CP) induced liver injury. Methodology: Q-ORMOSIL nanoparticles were synthesized and characterized using UV-Vis spectroscopy, TEM, Zeta sizer, FTIR and EDX. Further, encapsulation efficiency and in vitro release kinetic study was done. Q-ORMOSIL nanoparticles surface were modified with lactobionic acid, a ligand for the asialoglycoprotein receptor on the hepatocyte surface. The hepatoprotective effects of Q-ORMOSIL and LA-Q-ORMOSIL nanoparticles were evaluated in vivo. Cyclophosphamide (20 mg/kg/day, i.p) was co-administered for seven days with bulk quercetin (50mg/kg/day) and quercetin nanoparticles (50µg/kg/day). After seven days, the number of biomarkers for liver function test and oxidative stress were determined in liver homogenate. Histopathological changes were also analyzed in control and treated liver tissues. Results: Physiochemical characterization of LA-Q-ORMOSIL nanoparticles depicts that the particles formed were of approx. 80 nm, spherical, monodispersed in nature and showed sustain drug release in in vitro study. Our results further suggested that Q-ORMOSIL and LA-Q-ORMOSIL nanoparticles significantly decreased tissue TBARS, ROS levels and ALT, AST, and ALP activities compared to CP induced group. On the other hand, tissue antioxidant levels (GSH, GST, and catalase) showed a significant increase in LA-Q-ORMOSIL treated group compared to the CP treated group confirming its high therapeutic efficacy during liver injury. Conclusion: Targeted nanoquercetin demonstrated a significant hepatoprotective effect compared to bulk quercetin against CP-induced hepatotoxicity and it considerably reduced bulk quercetin dose level to many folds. Bulk quercetin has low bioavailability and thus, from obtained data we suggest that LA-Q-ORMOSIL nanoparticles provide high therapeutic value in protecting experimental animals against CP-induced liver injury. We also propose multifunctional dye-doped LA-modified ORMOSIL nanoparticles for future studies in facilitating nanoparticles uptake to hepatocytes for liver diagnosis and treatment.


Assuntos
Ciclofosfamida/efeitos adversos , Dissacarídeos/química , Fígado/patologia , Nanopartículas/química , Quercetina/farmacologia , Dióxido de Silício/química , Alanina Transaminase/metabolismo , Fosfatase Alcalina/metabolismo , Animais , Antioxidantes/farmacologia , Aspartato Aminotransferases/metabolismo , Catalase/metabolismo , Liberação Controlada de Fármacos , Cinética , Fígado/efeitos dos fármacos , Masculino , Nanopartículas/ultraestrutura , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
20.
Mediators Inflamm ; 2019: 1468502, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31780857

RESUMO

The literature shows that phenolic compounds possess important antioxidant and anti-inflammatory activities; however, the mechanism underlying these effects is not elucidated yet. The genus Calea is used in folk medicine to treat rheumatism, respiratory diseases, and digestive problems. In this context, some phenolic compounds were isolated with high purity from Calea uniflora Less. and identified as noreugenin (NRG) and α-hydroxy-butein (AH-BU). The aim of this study was to analyze the effect of these compounds on cell viability, the activity of myeloperoxidase (MPO), and apoptosis of mouse neutrophils using ex vivo tests. Furthermore, the effect of these compounds on the cytokines, interleukin 1 beta (IL-1ß), interleukin 17A (IL-17A), and interleukin 10 (IL-10), and oxidative stress was investigated by analyzing lipid peroxidation (the concentration of thiobarbituric acid reactive substances (TBARS)) and activities of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST), using a murine model of neutrophilic inflammation. The NRG and AH-BU reduce MPO activity and increase neutrophil apoptosis (p < 0.05). These compounds reduced the generation of oxygen reactive species and IL-1ß and IL-17A levels but increased IL-10 levels (p < 0.05). This study demonstrated that NRG and AH-BU show a significant anti-inflammatory effect by inhibiting the MPO activity and increasing neutrophil apoptosis in primary cultures of mouse neutrophils. These effects were at least partially associated with blocking reactive species generation, inhibiting IL-1ß and IL-17A, and increasing IL-10 levels.


Assuntos
Antioxidantes/uso terapêutico , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Fenóis/uso terapêutico , Pleurisia/tratamento farmacológico , Animais , Antioxidantes/química , Catalase/metabolismo , Modelos Animais de Doenças , Feminino , Glutationa Transferase/metabolismo , Interleucina-10/metabolismo , Interleucina-17/metabolismo , Interleucina-1beta/metabolismo , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Fenóis/química , Pleurisia/metabolismo , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
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