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1.
Cell Mol Biol (Noisy-le-grand) ; 65(2): 69-74, 2019 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-30860476

RESUMO

Obesity among children has emerged as a serious public health problem. The growing prevalence of childhood obesity has led to the appearance of serious complications, including a chronic systemic inflammation associated with oxidative stress.  In the present study, we analysed the interaction between two genes related with iron metabolism - HFE and haptoglobin - and the plasmatic concentration of glutathione, as a way to evaluate the antioxidant response capacity in obesity. To achieve this, 118 obese children and 89 eutrophic children were recruited for the study. Results showed that although obese children present a significantly decreased tGSH levels, once we analysed separately children based on their haptoglobin phenotype, the decreased tGSH levels is significant only for the Hp 2 allele. Additionally, Hp 2.2 obese children carrying H63D polymorphism show significantly lower tGSH/GSSG values. Our results found an association of haptoglobin and HFE with oxidative stress in childhood obesity.


Assuntos
Predisposição Genética para Doença , Glutationa/sangue , Haptoglobinas/genética , Proteína da Hemocromatose/genética , Obesidade/sangue , Obesidade/genética , Estudos de Casos e Controles , Criança , Feminino , Dissulfeto de Glutationa/sangue , Humanos , Masculino , Fenótipo
2.
Artigo em Inglês | MEDLINE | ID: mdl-30445289

RESUMO

Variability in the levels of GSH and GSSG in plasma is suggested to derive from inadequate pre-processing methods. The aim of this study was to develop a protocol for comparable and reliable measurements of GSH/GSSG. Venous blood from 8 healthy individuals were collected and divided into 7 different pre-processing procedures. For three of the samples an extraction mixture was added after 0 (baseline), 4 and 8 min and for three of the samples the extraction mixture was added at different times during defrost. A worst case scenario where a sample was left in a cool box during 6 h was also included. The samples were analyzed with UHPLC-ESI-MSMS. A large difference in the levels of GSH and GSSG were identified and it was clearly associated with the sample handling procedures. A sample left untreated for 4 min will have significantly reduced amount of GSH. Stability tests showed that the level of GSH was reduced after 3 months in -80 °C.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Dissulfeto de Glutationa/sangue , Dissulfeto de Glutationa/química , Glutationa/sangue , Glutationa/química , Estabilidade de Medicamentos , Humanos , Modelos Lineares , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem/métodos
3.
Vopr Pitan ; 87(5): 13-19, 2018.
Artigo em Russo | MEDLINE | ID: mdl-30592886

RESUMO

It is assumed that in the progression of obesity, complicated by fatty hepatosis in adolescents, a significant role is given to the reactions of oxidative stress with deficiency of antioxidant factors. However, an important factor that remains outside the field of view of researchers is the ethnicity of the patient, which is an important element in the development of a personalized approach in the treatment and prevention of diseases. In connection with this, the purpose of this study was to study the changes in the lipid peroxidation-antioxidant defense processes in adolescent Mongoloids with exogenously constitutional obesity complicated by fatty hepatosis. 18 adolescent boys with fatty hepatosis were examined on the background of exogenous-constitutional obesity of the first degree; 38 adolescent boys with exogenously constitutional obesity without changes in the liver and 37 practically healthy adolescents (control group). All subjects surveyed for ethnicity belonged to the Mongoloids. Spectrophotometric and fluorometric methods were used in the research. The results of the study indicated a high intensity of lipid peroxidation reactions in Mongoloid boys with obesity and fatty hepatosis relative to control values: an increase in blood plasma content of compounds with unsaturated double bonds (p<0.001), diene conjugates (p=0.0012), ketodienes and conjugated trienes (p<0.0001), in the absence of significant differences in the level of TBA-active products. Increased values of total antioxidant activity in blood plasma (p=0.0023) and erythrocyte superoxide dismutase activity (p=0.0072), decreased levels of fat-soluble vitamins in blood plasma [α-tocopherol (p<0.0001) and retinol (p=0.0011)] and oxidized form of glutathione in erythrocytes (p=0.0083) have been found. The pronounced insufficiency of fatsoluble vitamins - α-tocopherol and retinol in patients of the main group was also noted in comparison with patients without morphological changes in the liver. Thus, in teenage Mongoloids with exogenously constitutional obesity and fatty hepatosis, it is possible to recommend antioxidant drugs in addition to basic metabolic therapy.


Assuntos
Grupo com Ancestrais do Continente Asiático , Fígado Gorduroso/sangue , Peroxidação de Lipídeos , Obesidade/sangue , Adolescente , Antioxidantes/metabolismo , Eritrócitos/metabolismo , Dissulfeto de Glutationa/sangue , Humanos , Masculino , Vitamina A/sangue , alfa-Tocoferol/sangue
4.
Arch Endocrinol Metab ; 62(5): 545-551, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30462808

RESUMO

OBJECTIVE: Evaluate the relationship between exogenous subclinical hyperthyroidism and oxidative stress through the analysis of the redox profile of patients with subclinical hyperthyroidism exogenous (SCH) grade I (TSH = 0.1 to 0.4 IU/mL) and grade II (TSH < 0.1 IU/mL). SUBJECTS AND METHODS: We analyzed 46 patients with SCH due to the use of TSH suppressive therapy with LT4 after total thyroidectomy along with 6 control euthyroid individuals (3M and 3W). Patients were divided into two groups, G1 with TSH ≥ 0.1-0.4 IU/mL (n = 25; and 7M 14W) and G2 with TSH < 0.1 IU/mL (n = 25; and 4M 21W). Venous blood samples were collected to measure the levels of markers for oxidative damage (TBARS, FOX and protein carbonylation), muscle and liver damage (CK, AST, ALT, GGT) and antioxidants (GSH, GSSG and catalase). RESULTS: Individuals in G2 showed a GSH/GSSG ratio ~ 30% greater than those in G1 (p = 0.004) and a catalase activity that was 4 times higher (p = 0.005). For lipid peroxidation, the levels measured in G2 were higher than both control and G1 (p = 0.05). No differences were observed for both protein carbonyl markers. G1 and G2 presented with greater indications of cell injury markers than the control group. CONCLUSION: TSH suppression therapy with LT4 that results in subclinical hyperthyroidism can cause a redox imbalance. The greater antioxidant capacity observed in the more suppressed group was not sufficient to avoid lipid peroxidation and cellular damage.


Assuntos
Hipertireoidismo/tratamento farmacológico , Tireotropina/antagonistas & inibidores , Tiroxina/farmacologia , Adulto , Estudos de Casos e Controles , Catalase/sangue , Estudos Transversais , Feminino , Glutationa/sangue , Dissulfeto de Glutationa/sangue , Humanos , Hipertireoidismo/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fenóis/sangue , Carbonilação Proteica , Valores de Referência , Estatísticas não Paramétricas , Sulfóxidos/sangue , Substâncias Reativas com Ácido Tiobarbitúrico/análise
5.
Molecules ; 23(10)2018 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-30274319

RESUMO

Glutathione (γ-glutamyl-cysteinyl-glycine; also known as GSH) is an endogenous antioxidant that plays a crucial role in cell defense mechanisms against oxidative stress. It is thus not surprising that this molecule can serve as a biomarker for oxidative stress monitoring. As capillary blood is a highly accessible target for biomarking, it is a valuable bodily fluid for diagnosing human GSH levels. This study focused on the optimization of GSH measurements from micro volumes of capillary blood prior to using electrochemical detection. The optimization of experimental parameters, including the sample volume and its stability, was performed and evaluated. Moreover, we tested the optimized method as part of a short-term study. The study consisted of examining 10 subjects within 96 h of their consumption of high amounts of antioxidants, attained from a daily dose of 2 g/150 mL of green tea. The subjects' capillary blood (5 µL) was taken at 0 h, 48 h, and 96 h for subsequent analysis. The short-term supplementation of diet with green tea showed an increase of GSH pool by approximately 38% (between 0 and 48 h) within all subjects.


Assuntos
Glutationa/sangue , Chá/química , Adulto , Capilares , Dieta , Técnicas Eletroquímicas , Feminino , Dissulfeto de Glutationa/sangue , Humanos , Masculino
6.
Food Funct ; 9(11): 5891-5902, 2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30375606

RESUMO

Acetaminophen (APAP) is commonly used to relieve pain and fever in a clinical setting, but its excessive use can lead to serious hepatotoxicity. Our previous study demonstrated that polydatin (PD) can effectively attenuate d-galactose- and alcohol-induced hepatotoxicity, however, its effect on APAP-induced hepatotoxicity is still unknown. In this study, we explore the protective effect and potential mechanism of PD against APAP-induced hepatotoxicity in mice. The results indicate that PD effectively improves the survival of mice with APAP-induced hepatotoxicity, significantly alleviating histopathologic alterations in the liver, and decreasing the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). PD significantly and dose-dependently reduces oxidative stress by lowering the content of oxidized glutathione (GSSG), reactive oxygen species (ROS), nitric oxide (NO) and malonaldehyde (MDA), while enhancing the hepatic activities of glutathione (GSH), glutathione peroxidase (GSH-Px) and the GSH/GSSG ratio. Meanwhile, PD also substantially inhibits the levels and mRNA expressions of inducible nitric oxide synthase (iNOS) and NADPH oxidase 2 (NOX2). Additionally, PD markedly arrests apoptosis by assuaging TUNEL-positive hepatocytes and the apoptotic index, decreasing the levels and expression of cytochrome c (CytC), cleaved-caspase-9, apoptotic protease activating factor 1 (Apaf-1), cleaved-caspase-3, and Bax and increasing the level and expression of Bcl-2. Overall, PD pretreatment shows a potent protective effect against APAP-induced hepatotoxicity by relieving oxidative stress and inhibiting apoptosis.


Assuntos
Acetaminofen/toxicidade , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Glucosídeos/farmacologia , Substâncias Protetoras/farmacologia , Estilbenos/farmacologia , Alanina Transaminase/sangue , Animais , Antioxidantes/metabolismo , Fator Apoptótico 1 Ativador de Proteases/genética , Fator Apoptótico 1 Ativador de Proteases/metabolismo , Aspartato Aminotransferases/sangue , Caspase 3/genética , Caspase 3/metabolismo , Caspase 9/genética , Caspase 9/metabolismo , Glutationa/sangue , Dissulfeto de Glutationa/sangue , Dissulfeto de Glutationa/metabolismo , Glutationa Peroxidase/sangue , Glutationa Peroxidase/metabolismo , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Malondialdeído/sangue , Camundongos , Camundongos Endogâmicos ICR , NADPH Oxidase 2/genética , NADPH Oxidase 2/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
7.
J Occup Environ Med ; 60(11): e595-e601, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30252723

RESUMO

OBJECTIVE: Firefighters (FFs) involved in fire suppression have the greatest on-duty risk of cardiovascular disease (CVD), which may be caused by oxidative stress (OS). METHODS: Healthy, active FFs performed a victim "search and clear" exercise involving three conditions: (1) no heat, (2) heat + antioxidant, and (3) heat + placebo. Blood samples were analyzed for OS markers glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD), catalase (CAT), and advanced oxidation protein products (AOPP). RESULTS: Increased GSH was found during both heat conditions compared with no heat. CAT activity was higher immediately post exercise. AOPP was reduced post exercise. CONCLUSIONS: Antioxidant supplementation did not impact the OS response to exercise. Added heat did not cause OS and exercise resulted in reductions in OS markers. These findings can be attributed to the training status of the FFs involved.


Assuntos
Antioxidantes/administração & dosagem , Curcumina/administração & dosagem , Bombeiros , Temperatura Alta , Estresse Oxidativo , Esforço Físico/fisiologia , Adulto , Produtos da Oxidação Avançada de Proteínas/sangue , Biomarcadores/sangue , Catalase/sangue , Estudos Cross-Over , Método Duplo-Cego , Fogo , Dissulfeto de Glutationa/sangue , Frequência Cardíaca , Humanos , Masculino , Superóxido Dismutase/sangue
8.
Einstein (Sao Paulo) ; 16(3): eAO4190, 2018.
Artigo em Português, Inglês | MEDLINE | ID: mdl-30110067

RESUMO

Objective To investigate the relation between oxidative stress markers, human papillomavirus infection and cervical cancer precursor lesions. Methods The study comprised women aged 14 to 60 years living in communities located by Amazon rivers in the state of Pará (Itaituba, Limoeiro do Ajuru and Bragança, 126, 68 and 43 women respectively). Papanicolau smears and polymerase chain reaction tests for human papillomavirus DNA detection were performed. Blood samples were collected to test malondialdehyde, total and oxidized glutathione levels. Results Malondialdehyde, total and oxidized glutathione concentrations did not differ significantly (p>0.05) between women with and without low-grade squamous intraepithelial lesions across communities. Malondialdehyde levels (8.02nmols/mL) were almost five times higher in human papillomavirus-positive compared to human papillomavirus-negative women (1.70nmols/mL) living in Itaituba (statistically significant difference; p<0.05). Malondialdehyde levels did not differ significantly (p>0.05) between human papillomavirus-positive and human papillomavirus-negative women living in remaining communities. Significant (p<0.05) differences in total glutathione levels between human papillomavirus-positive and human papillomavirus-negative women (8.20µg/mL and 1.47µg/mL, respectively) were limited to those living in Bragança. Conclusion Malondialdehyde and total glutathione levels were significantly associated with human papillomavirus infection. However, lack of similar associations with squamous lesions suggest oxidative stress alone does not explain correlations with cervical carcinogenesis. Other factors may therefore be involved.


Assuntos
Dissulfeto de Glutationa/sangue , Glutationa Peroxidase/sangue , Malondialdeído/sangue , Estresse Oxidativo/fisiologia , Infecções por Papillomavirus/sangue , Lesões Intraepiteliais Escamosas Cervicais/sangue , Neoplasias do Colo do Útero/sangue , Adolescente , Adulto , Biomarcadores Tumorais/sangue , Brasil , Estudos Transversais , DNA Viral , Feminino , Humanos , Pessoa de Meia-Idade , Teste de Papanicolaou , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Reação em Cadeia da Polimerase , Valores de Referência , Rios , Índice de Gravidade de Doença , Lesões Intraepiteliais Escamosas Cervicais/virologia , Estatísticas não Paramétricas , Neoplasias do Colo do Útero/virologia , Adulto Jovem
9.
Anal Bioanal Chem ; 410(27): 7153-7161, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30151684

RESUMO

Currently, the measure of the oxidative stress, from oxidized and reduced glutathione (GSSG and GSH respectively), for large cohorts of samples, is generally limited to spectrometric methods. In this study, a high-throughput assay for GSH after derivatization with N-ethylmaleimide and GSSG in blood sample was developed with an analysis time of 1.5 min. The method combines protein precipitation and a short LC (10-mm length) column where compounds were trapped in front-flush mode and eluted in back-flush mode. This setup is combined with modifier-assisted differential ion mobility spectrometry (DMS, SelexIon) and detection is performed in the selected reaction monitoring mode using positive electrospray ionization. In DMS, various modifiers were investigated including N2, methanol, toluene, ethanol, acetonitrile, and isopropanol to improve assay selectivity. Using EtOH as modifier, the limit of quantification (LOQ) was found to be 0.4 µM for GSSG and 3.2 µM for GS-N-ethylmaleimide (NEM) using a blood volume of 60 µL. The method is linear over a wide dynamic concentration range of 0.4 to 400 µM for GSSG and from 3.2 to 3200 µM for GS-NEM. The inter-assay precision of QC samples were ≤ 6.7%, with accuracy values between 98.3 and 103%. The method was further cross-validated with a LC Hypercarb-DMS-MS/MS method by the analysis of human blood samples. The bias between both assays ranged from - 0.3 to 0.2%. Graphical abstract ᅟ.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Dissulfeto de Glutationa/sangue , Glutationa/sangue , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/instrumentação , Desenho de Equipamento , Humanos , Limite de Detecção , Oxirredução , Estresse Oxidativo , Reprodutibilidade dos Testes
10.
Int J Mol Med ; 42(4): 1885-1898, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30015864

RESUMO

A total of 32 electrohypersensitivity (EHS) self­reporting patients were serially included in the present prospective study for oxidative stress and antioxidative stress response assessment. All thiobarbituric acid­reactive substances (TBARs) were measured in the plasma, particularly malondialdehyde (MDA) for lipid peroxidation; additional measurements included total thiol group molecules, reduced glutathione (GSH), oxidized glutathione (GSSG) for oxidative stress assessment and nitrotyrosine, a marker of peroxynitrite­induced oxidative/nitrosative stress. In addition, the activity of Cu­Zn superoxide dismutase (SOD1) was measured in red blood cells (RBCs) and glutathione reductase (GR) and glutathione peroxidase (GPx) in RBCs and plasma. Depending of the biomarker considered, 30­50% of EHS self­reporting patients presented statistically significantly increased TBARs, MDA, GSSG and NTT mean plasmatic level values in comparison with normal values obtained in healthy controls (P<0.0001). By contrast, there were no plasmatic level values above the upper normal limits for GSH, GSH/GSSG ratio, total glutathione (GluT) and GSH/GluT ratio, and values for these GSH­associated biomarkers were statistically significantly decreased in 20­40% of the patients (P<0.0001). Furthermore, in RBCs, mean SOD1 and GPx activities were observed to be statistically significantly increased in ~60% and 19% (P<0.0001) of the patients, respectively, while increased GR activity in RBCs was observed in only 6% of the patients. The present study reports for the first time, to the best of our knowledge, that overall ~80% of EHS self­reporting patients present with one, two or three detectable oxidative stress biomarkers in their peripheral blood, meaning that these patients­as is the case for cancer, Alzheimer's disease or other pathological conditions­present with a true objective new pathological disorder.


Assuntos
Eritrócitos/metabolismo , Dissulfeto de Glutationa/sangue , Glutationa Peroxidase/sangue , Glutationa Redutase/sangue , Estresse Oxidativo , Autorrelato , Superóxido Dismutase-1/sangue , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
11.
J Cancer Res Ther ; 14(2): 428-431, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29516932

RESUMO

Background and Aim: Squamous cell carcinoma (SCC) is the most common type of oral cancer, and it is important for it to be diagnosed in early stages. Researchers are interested in exploring the possibility of using biomarkers in the diagnosis of SCC in early stages. One of the detectable biomarkers in the serum is glutathione. Glutathione includes two forms: reduced form (or GSH) and oxidized form (or GSSG). The GSH/GSSG ratio tends to decrease in severe oxidative stress. The aim of this study was to assess the serum levels of GSH and GSSG as well as GSH/GSSG as total antioxidant capacity in patients with head and neck SCC (HNSCC) and to subsequently compare them with healthy controls. Materials and Methods: Twenty HNSCC patients as well as twenty healthy controls were included in the study. A blood sample of 5 ml was obtained from both the case and control groups. GSH, GSSG, and total antioxidant capacity were measured spectrophotometrically. Results: No significant difference in the level of GSSG was observed in the patients from the case and control groups (P = 0.796), whereas the level of GSH and GSH/GSSG was significantly lower in the case group (P = 0.002, P = 0.011, respectively). There was no significant relationship between the level of GSH, GSSG, and total antioxidant capacity, on the one hand, and the stage and grade of the tumor, on the other hand. Conclusion: Since the levels of GSH and GSH/GSSG were significantly lower in the case group, GSH/GSSG could be used as a prognostic factor for the early diagnosis of HNSCC.


Assuntos
Antioxidantes , Biomarcadores/sangue , Carcinoma de Células Escamosas/sangue , Dissulfeto de Glutationa/sangue , Glutationa/sangue , Neoplasias de Cabeça e Pescoço/sangue , Idoso , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Oxirredução , Estresse Oxidativo , Carcinoma de Células Escamosas de Cabeça e Pescoço
12.
J Nutr ; 148(2): 245-253, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29490099

RESUMO

Background: Both systemic redox status and diet quality are associated with risk outcomes in chronic disease. It is not known, however, the extent to which diet quality influences plasma thiol/disulfide redox status. Objective: The purpose of this study was to investigate the influence of diet, as measured by diet quality scores and other dietary factors, on systemic thiol/disulfide redox status. Methods: We performed a cross-sectional study of 685 working men and women (ages ≥18 y) in Atlanta, GA. Diet was assessed by 3 diet quality scores: the Alternative Healthy Eating Index (AHEI), Dietary Approaches to Stop Hypertension (DASH), and the Mediterranean Diet Score (MDS). We measured concentrations of plasma glutathione (GSH), cysteine, their associated oxidized forms [glutathione disulfide (GSSG) and cystine (CySS), respectively], and their redox potentials (EhGSSG and EhCySS) to determine thiol/disulfide redox status. Linear regression modeling was performed to assess relations between diet and plasma redox after adjustment for age, body mass index (BMI), sex, race, and history of chronic disease. Results: MDS was positively associated with plasma GSH (ß = 0.02; 95% CI: 0.003, 0.03) and total GSH (GSH + GSSG) (ß = 0.02; 95% CI: 0.003, 0.03), and inversely associated with the CySS:GSH ratio (ß = -0.02; 95% CI: -0.04, -0.004). There were significant independent associations between individual MDS components (dairy, vegetables, fish, and monounsaturated fat intake) and varying plasma redox indexes (P < 0.05). AHEI and DASH diet quality indexes and other diet factors of interest were not significantly correlated with plasma thiol and disulfide redox measures. Conclusion: Adherence to the Mediterranean diet was significantly associated with a favorable plasma thiol/disulfide redox profile, independent of BMI, in a generally healthy working adult population. Although longitudinal studies are warranted, these findings contribute to the feasibility of targeting a Mediterranean diet to improve plasma redox status.


Assuntos
Índice de Massa Corporal , Cisteína/sangue , Cistina/sangue , Dieta Mediterrânea/estatística & dados numéricos , Dissulfeto de Glutationa/sangue , Adulto , Estudos Transversais , Dieta , Dissulfetos/sangue , Feminino , Glutationa/sangue , Humanos , Hipertensão/dietoterapia , Masculino , Pessoa de Meia-Idade , Oxirredução , Compostos de Sulfidrila/sangue
13.
Eur J Sport Sci ; 18(6): 832-841, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29575975

RESUMO

Using a controlled parallel group longitudinal trial design, we investigated the effects of different training interventions on the prooxidant/antioxidant status of elite athletes: living and training at moderate altitude for 3 (Hi-Hi3) and 4 weeks (Hi-Hi), and for 4 weeks too, living high and training high and low (Hi-HiLo) and living and training at sea level (Lo-Lo). From 61 swimmers, 54 completed the study. Nitrites, carbonyls, and lipid peroxidation (LPO) levels were assessed in plasma. Enzymatic antioxidants glutathione peroxidase (GPx) and glutathione reductase (GRd), and non-enzymatic antioxidants total glutathione (GST), reduced glutathione (GSH) and oxidized glutathione (GSSG) were analysed in the erythrocyte fraction. At the end of the intervention, nitrites levels were similar in all altitude groups but higher than in the Lo-Lo controls (P = .02). Hi-HiLo had greater GPx activity than Hi-Hi and Hi-Hi3 during most of the intervention (P ≤ .001). GRd activity was higher in Lo-Lo than in Hi-Hi at the end of the training camp (P ≤ .001). All groups showed increased levels of LPO, except Lo-Lo, and carbonyls at the end of the study (P ≤ .001). Training at altitude for 3 or 4 weeks drives oxidative stress leading to cellular damage mainly by worsening the antioxidant capacities. The GSSG/GSH ratio appears to be related to perceived exertion and fatigue. The stronger antioxidant defence showed by the Hi-HiLo group suggests an inverse relationship between redox alterations and performance. Further studies are required to investigate the role of oxidative stress in acclimatization, performance, and health.


Assuntos
Altitude , Atletas , Estresse Oxidativo , Condicionamento Físico Humano , Adolescente , Adulto , Antioxidantes/análise , Estudos Controlados Antes e Depois , Feminino , Glutationa/sangue , Dissulfeto de Glutationa/sangue , Glutationa Peroxidase/sangue , Glutationa Redutase/sangue , Humanos , Peroxidação de Lipídeos , Estudos Longitudinais , Masculino , Nitritos/sangue , Adulto Jovem
14.
Eur J Clin Nutr ; 72(5): 744-751, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29288250

RESUMO

BACKGROUND/OBJECTIVES: Disruptions in redox balance lead to oxidative stress, a promoter of morbidity in critical illness. This study aimed to: (1) characterize the plasma and alveolar thiol/disulfide redox pools, (2) examine their associations with alveolar macrophage phagocytosis, and (3) determine the effect of high dose vitamin D3 on plasma thiol/disulfide redox. SUBJECTS/METHODS: Subjects were 30 critically ill, ventilated adults in a double-blind randomized trial of high-dose (250 000 or 500 000 IU) vitamin D3 or placebo. Baseline bronchoalveolar lavage fluid (BALF) samples were analyzed for determination of alveolar phagocytosis index (PI) and for concentrations of glutathione (GSH), glutathione disulfide (GSSG), cysteine (Cys), cystine (CySS), and their respective redox potentials (EhGSSG and EhCySS). Plasma redox outcomes were assessed at baseline and days 7 and 14. RESULTS: Baseline plasma Cys was inversely associated with alveolar PI (ρ = -0.69, P = 0.003), and EhCySS was positively associated with PI (ρ = 0.61, P = 0.01). Over time, among all subjects there was an increase in plasma GSH levels and a decrease in EhGSSG (P < 0.01 for both), with no difference by treatment group. Vitamin D3 decreased oxidized plasma GSSG to a more normal state (P for group x time = 0.009). CONCLUSIONS: Oxidative stress indicators were positively associated with alveolar macrophage phagocytic function in acutely ill ventilated adults. High-dose vitamin D3 decreased plasma GSSG concentrations, which suggests that vitamin D can possibly improve the oxidative stress environment.


Assuntos
Colecalciferol/uso terapêutico , Estado Terminal/terapia , Macrófagos Alveolares/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Respiração Artificial , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Cisteína/sangue , Cistina/sangue , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Glutationa/sangue , Dissulfeto de Glutationa/sangue , Humanos , Masculino , Pessoa de Meia-Idade
15.
Eur J Clin Nutr ; 72(1): 105-111, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28853742

RESUMO

BACKGROUND/OBJECTIVES: Glutathione (GSH) is the most abundant endogenous antioxidant and a critical regulator of oxidative stress. Maintenance of optimal tissues for GSH levels may be an important strategy for the prevention of oxidative stress-related diseases. We investigated if oral administration of liposomal GSH is effective at enhancing GSH levels in vivo. SUBJECTS/METHODS: A 1-month pilot clinical study of oral liposomal GSH administration at two doses (500 and 1000 mg of GSH per day) was conducted in healthy adults. GSH levels in whole blood, erythrocytes, plasma and peripheral blood mononuclear cells (PBMCs) were assessed in 12 subjects at the baseline and after 1, 2 and 4 weeks of GSH administration. RESULTS: GSH levels were elevated after 1 week with maximum increases of 40% in whole blood, 25% in erythrocytes, 28% in plasma and 100% in PBMCs occurring after 2 weeks (P<0.05). GSH increases were accompanied by reductions in oxidative stress biomarkers, including decreases of 35% in plasma 8-isoprostane and 20% in oxidized:reduced GSH ratios (P<0.05). Enhancements in immune function markers were observed with liposomal GSH administration including Natural killer (NK) cell cytotoxicity, which was elevated by up to 400% by 2 weeks (P<0.05), and lymphocyte proliferation, which was elevated by up to 60% after 2 weeks (P<0.05). Overall, there were no differences observed between dose groups, but statistical power was limited due to the small sample size in this study. CONCLUSIONS: Collectively, these preliminary findings support the effectiveness of daily liposomal GSH administration at elevating stores of GSH and impacting the immune function and levels of oxidative stress.


Assuntos
Biomarcadores/sangue , Glutationa/administração & dosagem , Glutationa/sangue , Imunidade/fisiologia , Lipossomos/administração & dosagem , Idoso , Citotoxicidade Imunológica/efeitos dos fármacos , Suplementos Nutricionais , Eritrócitos/química , Feminino , Dissulfeto de Glutationa/sangue , Humanos , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Leucócitos Mononucleares/química , Leucócitos Mononucleares/efeitos dos fármacos , Ativação Linfocitária/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Pennsylvania
16.
Molecules ; 22(11)2017 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-29112153

RESUMO

Despite being a plant by-product, chokeberry pomace is believed to exert some therapeutic effects because it is one of the richest sources of highly bioavailable non-enzymatic antioxidants. The aim of this study was to determine the functionality of bioactive compounds present in the Aronia melanocarpa pomace (chokeberry) based on enzymatic and non-enzymatic parameters related to the active defence of liver and blood against the effects of oxidative stress. The experiment was conducted with 48 lambs of two breeds-Polish Merino and Wrzosówka. Experimental groups were administered the basic feed with the addition of 150 g or 300 g of black chokeberry pomace per each kg of the complete feed. The activities of antioxidative enzymes (superoxide dismutase, glutathione peroxidase), peptides (glutathione, glutathione disulfide), and a lipid peroxidation indicator (malondialdehyde), as well as the capacity of non-enzymatic antioxidants were investigated. The results proved a strong effect of bioactive compounds contained in the black chokeberry pomace on the estimated parameters. The inclusion of chokeberry pomace in feed mixtures brought many benefits linked with the antioxidative protection. Parameters responsible for the oxidative status were significantly modified despite the commonly-held view about a limited possibility of transferring phenolic compounds to the organs.


Assuntos
Antioxidantes/administração & dosagem , Fígado/metabolismo , Photinia/química , Extratos Vegetais/administração & dosagem , Animais , Antioxidantes/farmacologia , Glutationa/sangue , Glutationa/metabolismo , Dissulfeto de Glutationa/sangue , Dissulfeto de Glutationa/metabolismo , Glutationa Peroxidase/sangue , Glutationa Peroxidase/metabolismo , Malondialdeído/sangue , Malondialdeído/metabolismo , Extratos Vegetais/farmacologia , Ovinos , Superóxido Dismutase/sangue , Superóxido Dismutase/metabolismo
17.
Anal Chem ; 89(20): 10726-10733, 2017 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-28853561

RESUMO

The simultaneous electrochemical quantification of oxidized (GSSG) and reduced glutathione (GSH), biomarkers of oxidative stress, is demonstrated in biological fluids. The detection was accomplished by the development of a modified carbon electrode and was applied to the analysis of biological fluids of model organisms under oxidative stress caused by lead intoxication. Nanocomposite molecular material based on cobalt phthalocyanine (CoPc) and multiwalled carbon nanotubes functionalized with carboxyl groups (MWCNTf) was developed to modify glassy carbon electrodes (GCE) for the detection of reduced and oxidized glutathione. The morphology of the nanocomposite film was characterized by scanning electron microscopy (SEM) and profilometry. The electrochemical behavior of the modified electrode was assessed by cyclic voltammetry (CV) to determine the surface coverage (Γ) by CoPc. The electrocatalytic behavior of the modified electrode toward reduced (GSH) and oxidized (GSSG) forms of glutathione was assessed by CV studies at physiological pH. The obtained results show that the combined use of CoPc and MWCNTf results in an electrocatalytic activity for GSH oxidation and GSSG reduction, enabling the simultaneous detection of both species. Differential pulse voltammetry reveals detection limits of 100 µM for GSH and 8.3 µM for GSSG, respectively. The potential interference from ascorbic acid, cysteine, glutamic acid, and glucose was also studied, and the obtained results show limited effects from these species. Finally, the hybrid electrode was used for the determination of GSH and GSSG in rat urine and plasma samples, intoxicated or not by lead. Both glutathione forms were detected in these complex biological matrixes without any pretreatment. Our results portray the role of GSH and GSSG as markers of oxidative stress in live organisms under lead intoxication.


Assuntos
Técnicas Eletroquímicas/métodos , Dissulfeto de Glutationa/análise , Glutationa/análise , Animais , Líquidos Corporais/metabolismo , Eletrodos , Glutationa/sangue , Glutationa/urina , Dissulfeto de Glutationa/sangue , Dissulfeto de Glutationa/urina , Indóis/química , Limite de Detecção , Masculino , Nanocompostos/química , Nanotubos de Carbono/química , Compostos Organometálicos/química , Oxirredução , Estresse Oxidativo , Ratos , Ratos Wistar
18.
BMC Pediatr ; 17(1): 172, 2017 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-28728551

RESUMO

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is commonly detected during mass screening for neonatal disease. We developed a method to measure reduced glutathione (GSH) and glutathione disulfide (GSSG) using tandem mass spectrometry (MS/MS) for detecting G6PD deficiency. METHODS: The concentration of GSH and the GSH/GSSG ratio in newborn dry-blood-spot (DBS) screening and in blood plus sodium citrate for test confirmation were examined by MS/MS using labeled glycine as an internal standard. RESULTS: G6PD-deficient newborns had a lower GSH content (242.9 ± 15.9 µmol/L)and GSH/GSSG ratio (14.9 ± 7.2) than neonatal controls (370.0 ± 53.2 µmol/L and 46.7 ± 19.6, respectively). Although the results showed a significance of P < 0.001 for DBS samples plus sodium citrate that were examined the first day after preparation, there were no significant differences in the mean GSH concentration and GSH/GSSG ratio between the G6PD deficiency-positive and negative groups when examined three days after sample preparation. CONCLUSION: The concentration of GSH and the ratio of GSH/GSSG in blood measured using MS/MS on the first day of sample preparation are consistent with G6PD activity and are helpful for diagnosing G6PD deficiency.


Assuntos
Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Glutationa/sangue , Triagem Neonatal/métodos , Espectrometria de Massas em Tandem , Biomarcadores/sangue , Estudos de Casos e Controles , Teste em Amostras de Sangue Seco , Deficiência de Glucosefosfato Desidrogenase/sangue , Dissulfeto de Glutationa/sangue , Humanos , Recém-Nascido
19.
J Affect Disord ; 219: 193-200, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28564628

RESUMO

BACKGROUND: Oxidative stress is implicated in both depression and anxiety, but it is currently unclear whether this relates to syndromal diagnoses or trans-diagnostic dimensional symptoms. We examined the relationship between oxidative stress and severity of depression and anxiety symptoms in individuals with Major Depressive Disorder (MDD). METHODS: Plasma oxidative stress markers F2-isoprostanes and oxidized glutathione (GSSG), and the antioxidant reduced glutathione (GSH), were assessed in 69 physically healthy, medication-free MDD subjects. Symptoms of anxiety and depression were assessed using the Hamilton Anxiety (HAM-A) and Hamilton Depression (HAM-D) Rating Scales. Total HAM-A and HAM-D scores, along with "core" anxiety and depression subscales, and individual HAM-D items "psychic anxiety" and "depressed mood," were related to oxidative stress markers. Analyses controlled for age, sex, BMI, and smoking. RESULTS: Total HAM-A ratings were positively associated with F2-isoprostanes (ß=.26, p=.042) and GSSG (ß=.25, p=.049), but not GSH (ß=.05, p=.711). Core anxiety severity was positively associated with F2-isoprostanes (ß=.34, p=.012) and GSSG, although this did not reach significance (ß=.24, p=.074). None of the biological markers were significantly associated with total HAM-D or core depression ratings (all p>.13). Subjects scoring high on "psychic anxiety" had elevated F2-isoprostanes (p=.030) and GSSG (p=.020). This was not seen with "depressed mood" scores (all p>.12). LIMITATIONS: We assessed peripheral oxidative markers, but their relationship to the brain is unclear. CONCLUSIONS: Oxidative stress is more closely related to anxiety than depression symptoms in MDD. This highlights the importance of relating oxidative stress to specific symptoms and could provide new insights into the biological correlates of affective disorders.


Assuntos
Ansiedade/sangue , Depressão/sangue , Transtorno Depressivo Maior/sangue , Estresse Oxidativo/fisiologia , Adulto , Biomarcadores/sangue , F2-Isoprostanos/sangue , Feminino , Glutationa/sangue , Dissulfeto de Glutationa/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença
20.
Lupus ; 26(11): 1166-1173, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28420061

RESUMO

Metabolomics has been applied to explore altered metabolite profiles in disease and identify unique metabolic signatures specific to certain pathologies. The aim of the current study is to characterize the metabolic profile of patients diagnosed with lupus nephritis (LN) and explore new insights into underlying disease processes. A metabolomic approach using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS) was developed in serum samples from 32 LN patients, 30 idiopathic nephrotic syndrome (INS) patients and 28 healthy controls (HCs). Potential biomarkers were screened from orthogonal projection to latent structures discriminate analysis (OPLS-DA) and further evaluated by receiver operating characteristic analysis (ROC). A total of 14 potential biomarkers were screened and tentatively identified for LN patients compared to HCs. Compared to HCs and INS patients, the LN patients had increased serum levels of sorbitol and glycocholic acid metabolites and decreased levels of cortisol, creatinine and L-aspartyl-L-phenylalanine. A panel of three metabolomics (theophylline, oxidized glutathione and capric acid) was identified as biomarkers of LN with a sensitivity of 87.50% and a specificity of 67.86% using ROC analysis. Our results suggest that UPLC-HRMS based quantification of circulating metabolites was a useful tool for identification of biomarkers with the ability to segregate LN patients from INS patients and HCs. The potential biomarkers indicated that the LN metabolic disturbance may be closely associated with inflammation injury, oxidative stress and phospholipid metabolism.


Assuntos
Ácidos Decanoicos/sangue , Dissulfeto de Glutationa/sangue , Nefrite Lúpica/sangue , Metabolômica/métodos , Teofilina/sangue , Adulto , Área Sob a Curva , Biomarcadores/sangue , Estudos de Casos e Controles , Cromatografia Líquida de Alta Pressão , Análise Discriminante , Feminino , Humanos , Nefrite Lúpica/diagnóstico , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Reprodutibilidade dos Testes
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