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1.
Environ Pollut ; 254(Pt A): 112921, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31394349

RESUMO

The associations between bisphenol analogues (BPs) exposure and oxidative damage was explored in this 3-year longitudinal study of 275 school children in East China. Nine BPs in first morning urine samples were measured to assess BPs exposure, and 8-hydroxydeoxyguanosine (8-OHdG) and 8-oxo-7,8-dihydroguanosine (8-OHG) were measured as biomarkers of oxidative DNA and RNA damage. Linear mixed model (LMM) was used for repeated measures analysis. School children were mainly exposed to BPA, BPS, BPF, and BPAF (detection frequencies: 97.9%, 42.2%, 13.3%, and 12.8%) with median concentrations of 1.55, 0.355, 0.236 and 0.238 µg g-1Cre, respectively. An interquartile range (IQR) increase in urinary BPA was significantly associated with 12.9% (95% CI: 6.1%, 19.6%) increase in 8-OHdG and 19.4% (95% CI: 11.7%, 27.1%) increase in 8-OHG, and for total of BPs (the sum of BPA, BPS, BPF, and BPAF), they were 17.4% (95% CI: 8.9%, 26.0%) for 8-OHdG and 25.9% (95% CI: 16.1%, 35.7%) for 8-OHG, respectively. BPS was positively associated with 8-OHG, but not with 8-OHdG. The study found positive associations of urinary levels of BPA and total BPs with 8-OHdG and 8-OHG and indicated that BPs exposure might cause oxidative RNA damage.


Assuntos
Compostos Benzidrílicos/urina , Dano ao DNA , Desoxiguanosina/análogos & derivados , Exposição Ambiental/análise , Poluentes Ambientais/urina , Fenóis/urina , Compostos Benzidrílicos/toxicidade , Biomarcadores/urina , Criança , China , DNA , Desoxiguanosina/urina , Poluentes Ambientais/toxicidade , Humanos , Estudos Longitudinais , Oxirredução , Estresse Oxidativo , Fenóis/toxicidade , RNA , Projetos de Pesquisa
2.
Int J Occup Environ Med ; 10(3): 124-136, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31325295

RESUMO

BACKGROUND: Coke oven workers are exposed to polycyclic aromatic hydrocarbons (PAHs) with possible genotoxicity and carcinogenicity. Metabolizing enzymes genes and DNA repair genes are suspected to be correlated with the level of DNA damage. They may contribute to variable individual sensitivity to DNA damage induced by PAHs exposure at workplace. OBJECTIVE: To investigate the relationship between biomarkers of PAHs: 1-hydroxypyrene (1-OHP), DNA adducts, and 8-hydroxy-2-deoxyguanosine (8-OHdG) in coke oven workers, and to assess the role of cytochrome P2E1 (CYP2E1) gene expression and DNA repairing gene (XRCC1) polymorphism in detecting workers at risk. METHODS: 85 exposed workers and 85 unexposed controls were enrolled into this study. Urinary 1-OHP, 8-OHdG, and BPDE-DNA adduct were measured. CYP2E1 gene expression and genotyping of XRCC1 399 Arg/Gln were evaluated by real-time PCR. RESULTS: The median urinary 1-OHP levels (6.3 µmol/mol creatinine), urinary 8-OHdG (7.9 ng/mg creatinine), DNA adducts (6.7 ng/µg DNA) in the exposed group were significantly higher than those in the unexposed group. Carriers of the variant allele (Gln) of XRCC1 had the highest levels of 1-OHP, DNA adducts and 8-OHdG, and the lowest level of CYP2E1 gene expression. In exposed workers, significant positive correlations were found between 1-OHP level and each of the work duration, 8-OHdG, and DNA adducts levels. There was a significant negative correlation between 1-OHP level and CYP2E1 gene expression. Work duration and CYP2E1 gene expression were predictors of DNA adducts level; 1-OHP level and work duration were predictors of urinary 8-OHdG level. CONCLUSION: Workers with higher exposure to PAH were more prone to oxidative DNA damage and cancer development. DNA adducts level reflects the balance between their production by CYP2E1 and elimination by XRCC1 gene.


Assuntos
Citocromo P-450 CYP2E1/genética , Adutos de DNA/genética , Desoxiguanosina/análogos & derivados , Monitoramento Ambiental/métodos , Exposição Ocupacional/análise , Pirenos/urina , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/genética , 7,8-Di-Hidro-7,8-Di-Hidroxibenzo(a)pireno 9,10-óxido , Adulto , Biomarcadores/urina , Coque , Citocromo P-450 CYP2E1/biossíntese , Adutos de DNA/urina , Dano ao DNA/efeitos dos fármacos , Reparo do DNA/genética , Desoxiguanosina/urina , Egito , Humanos , Masculino , Pessoa de Meia-Idade , Hidrocarbonetos Policíclicos Aromáticos/urina , Polimorfismo Genético , Medição de Risco , Proteína 1 Complementadora Cruzada de Reparo de Raio-X/biossíntese , Adulto Jovem
3.
Lipids Health Dis ; 18(1): 111, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31077211

RESUMO

BACKGROUND: Hepatic lipase (HL, encoded by LIPC) is a glycoprotein primarily synthesized and secreted by hepatocytes. Previous studies had demonstrated that HL is crucial for reverse cholesterol transport and affects the metabolism, composition, and level of several lipoproteins. In current study, we investigated the association of LIPC (Lipase C, Hepatic Type) variants with circulating and urinary biomarker levels by using subgroup and mediation analyses. METHODS: A total of 572 participants from Taiwan were genotyped for three LIPC single nucleotide polymorphisms (SNPs) by using TaqMan assay. Fasting levels of glucose, lipid profile, inflammation markers, urine creatinine and 8-hydroxy deoxyguanosine (8-OHdG) were measured. The chi-square test, 2-sample t test and Analysis of variance (ANOVA) were used to examine differences among variables and genotype frequencies. RESULTS: SNPs rs2043085 and rs1532085 were significantly associated with urinary 8-OHdG levels, whereas all three SNPs were more significantly associated with Triglycerides (TG) or HDL-cholesterol (HDL-C) levels after additional adjustment for HDL-C or TG levels, respectively. Subgroup analyses revealed that the association of the LIPC SNPs with the levels of serum TG, HDL-C, and urinary 8-OHdG were predominantly observed in the men but not in the women. Differential associations of the LIPC SNPs with various lipid levels were observed in participants with different adiposity statuses. Mediation analyses indicated that TG levels acted as a suppressor masking the association of the LIPC genotypes with HDL-C levels, particularly in the men (Sobel test, all P < 0.01). CONCLUSION: Our data revealed that interaction and suppression effects mediated the pleiotropic association of the LIPC variants. The effects of the LIPC SNPs depended on sex, adiposity status, and TG levels. Thus, our findings can provide a method for identifying high-risk populations of cardiovascular diseases for clinical diagnosis.


Assuntos
Desoxiguanosina/análogos & derivados , Estudos de Associação Genética , Pleiotropia Genética , Lipase/genética , Lipídeos/sangue , Polimorfismo de Nucleotídeo Único/genética , Biomarcadores/sangue , HDL-Colesterol/sangue , Desoxiguanosina/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Obesidade/sangue , Obesidade/genética , Caracteres Sexuais , Triglicerídeos/sangue
4.
Talanta ; 201: 271-279, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31122423

RESUMO

In this work, an innovative aptamer-based magnetic adsorbent (Fe3O4@PDA-aptamer MNPs) was prepared by hydrothermal synthesis method followed by the surface functionalization of nanoparticles. After fixing in a steel stainless tube as sorbent of magnetic solid phase extraction (MSPE), an online magnetic solid phase extraction-high performance liquid chromatography-mass spectrometry (online-MSPE-HPLC-MS) method was developed and applied for the determination of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) simultaneously in urine. The synthesized sorbent presented outstanding features, including large specific surface area, high enrichment capacity and excellent stability. High throughput analysis can be achieved by affinity-specific adsorption of 8-OHdG and non-specific adsorption of OH-PAHs at the same time. In addition, online MSPE can greatly simplify the analysis process, reduce human errors and enhance the sensitivity. When compared with offline MSPE, a sensitivity enhancement of 30-400 times was obtained for the online method. Some experimental parameters such as the amount of the sorbent, sampling flow rate and sample volume, were optimized systematically. Under the optimal conditions, the limits of detection (LOD) were in the range of 0.028-0.114 ng mL-1, and the correlation coefficients (R2) were higher than 0.9962. The relative standard deviations (RSDs) were less than 16.1% (n = 5) and the recoveries ranged from 71% to 116%. The above results show that the rapid, sensitive and automated online-MSPE-HPLC-MS method has potential application in the simultaneous determination of 8-OHdG and PAHs in complex sample matrix to assess the environmental exposure level.


Assuntos
Aptâmeros de Nucleotídeos/química , Desoxiguanosina/análogos & derivados , Hidrocarbonetos Policíclicos Aromáticos/urina , Extração em Fase Sólida/métodos , Adolescente , Adsorção , Adulto , Sequência de Bases , Cromatografia Líquida de Alta Pressão , Desoxiguanosina/urina , Humanos , Limite de Detecção , Nanopartículas de Magnetita/química , Espectrometria de Massas , Adulto Jovem
5.
J Trace Elem Med Biol ; 54: 103-109, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31109599

RESUMO

Arsenic is a well-known toxic heavy metal that is naturally dispersed in groundwater. Whereas arsenic is widely accepted to be involved in oxidative stress damage, little is known about arsenic-induced oxidative damage in relationship to contaminated drinking water as a source. The aim of this study was to determine the association between arsenic exposure through drinking water and oxidative stress status by measuring levels of urinary 8-hydroxydeoxyguanosine (8-OHdG) as a biomarker of oxidative stress damage in a Myanmar population. A questionnaire-based survey and drinking water and urine sampling (n = 198) were performed to assess the association between arsenic exposure and urinary 8-OHdG concentration in the Ayeyarwady Region, Myanmar. Urinary arsenic concentrations were significantly correlated with drinking water arsenic concentrations (Spearman's rho = 0.32, p < 0.001). Multivariate linear regression analysis showed that higher urinary arsenic concentrations were significantly associated with higher 8-OHdG concentrations (coefficient = 0.09, 95% confidence interval, 0.03 - 0.15; p = 0.002). The present study identified that exposure to arsenic through drinking water could induce an increase in the urinary 8-OHdG concentration, reflecting increased oxidative DNA damage. These findings provide evidence that may explain the role of arsenic-induced oxidative stress in the pathophysiology of arsenic-induced diseases including cancers.


Assuntos
Arsênico/urina , Água Potável/efeitos adversos , Adulto , Estudos Transversais , Dano ao DNA/efeitos dos fármacos , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Masculino , Metais Pesados/urina , Pessoa de Meia-Idade , Análise Multivariada , Mianmar , Estresse Oxidativo/efeitos dos fármacos , Inquéritos e Questionários , Poluentes Químicos da Água
6.
Exp Oncol ; 41(1): 26-31, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30932412

RESUMO

Prognosis of metastatic colorectal cancer (mCRC) patients nowadays is an important subject in the field of oncology. R0-resection of colon with primary tumor and liver metastasis remains the only treatment which significantly improves survival rate. However, recent experimental data show that surgical trauma can indirectly stimulate tumor growth due to mitochondrial dysfunction and unregulated superoxide radical (O2-) generation. AIM: To study the clinical significance of 8-oxo-2'-deoxyguanosine (8-oxodGu) marker, to assess the oncological effects of warm ischemia of liver parenchyma on disease prognosis in patients with mCRC. MATERIAL AND METHODS: 69 urine 24-hour volume tests of patients with mCRC and 17 healthy individuals were studied. Urine 8-oxodGu level was measured using spectrophotometric method with pre-solid phase DNA extraction. The energy system and hepatocyte detoxification system state, levels of O2- in tumor tissue were determined using the method of electron paramagnetic resonance (EPR) and SpinTraps technology at room temperature. Experiments were carried out on a computerized EPR spectrometer RE-1307. EPR spectra were recorded at temperature of liquid nitrogen (196C) in paramagnetically pure quartz dewar on a computerized spectrometer PE-1307 with resonator H011. Error of the method of spectrum integration and spread of spectrum reproduction of one sample was not more than 3%. RESULTS: The average level of marker in healthy individuals was 0.244 day, whereas before the resection and on day 3 after the R0-resection of liver in mCRC patients was 3.42 day and 2.12 day (p < 0.05), respectively. On day 3 after the liver resection due to its metastatic lesions with a total duration of warm ischemia period < 30 min and > 30 min have had marker at level 2.108 day and 2.9883 day (p < 0.0001), respectively. The volume of metastatic tissue significantly and directly correlated with the level of urine 8-oxodGu (R2=0.54, 95% CI 0.0370.0991, p < 0.0001), also duration of surgical intervention (300 min) and duration of worm liver ischemia ( 30 min) during the surgery significantly increased urine level of 8-oxodGu (R2=0.54, 95% CI 0.001 0.004, p < 0.001). CONCLUSIONS: Warm liver ischemia (> 30 min), long-term surgical intervention ( 300 min) and metastatic tissue volume ( 12 cm3) in liver parenchyma in mCRC patients significantly increase urine 8-oxodGu levels. R0-resection of liver metastases in mCRC patients decreases urine 8-oxodGu levels already on day 3 after the surgery. 8-oxodGu is a new factor of oncological prognosis in patients with mCRC.


Assuntos
Neoplasias Colorretais/metabolismo , DNA/metabolismo , Oxirredução , Idoso , Biomarcadores , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Desoxiguanosina/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico
7.
Toxicol In Vitro ; 57: 194-202, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30853490

RESUMO

Maple syrup urine disease (MSUD) is an inherited deficiency of the branched-chain α-keto dehydrogenase complex, characterized by accumulation of the branched-chain amino acids (BCAAs) and their respective branched chain α-keto-acids (BCKAs), as well as by the presence of alloisoleucine (Allo). Studies have shown that oxidative stress is involved in the pathophysiology of MSUD. In this work, we investigated using the comet assay whether Allo, BCAAs and BCKAs could induce in vitro DNA damage, as well as the influence of l-Carnitine (L-Car) upon DNA damage. We also evaluated urinary 8-hydroxydeoguanosine (8-OHdG) levels, an oxidative DNA damage biomarker, in MSUD patients submitted to a restricted diet supplemented or not with L-Car. All tested concentrations of metabolites (separated or incubated together) induced in vitro DNA damage, and the co-treatment with L-Car reduced these effects. We found that Allo induced the higher DNA damage class and verified a potentiation of DNA damage induced by synergistic action between metabolites. In vivo, it was observed a significant increase in 8-OHdG levels, which was reversed by L-Car. We demonstrated for the first time that oxidative DNA damage is induced not only by BCAAs and BCKAs but also by Allo and we reinforce the protective effect of L-Car.


Assuntos
Aminoácidos/administração & dosagem , Carnitina/uso terapêutico , Dano ao DNA , Suplementos Nutricionais , Doença da Urina de Xarope de Bordo , Substâncias Protetoras/uso terapêutico , Aminoácidos/sangue , Aminoácidos/urina , Criança , Pré-Escolar , Ensaio Cometa , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Humanos , Doença da Urina de Xarope de Bordo/sangue , Doença da Urina de Xarope de Bordo/dietoterapia , Doença da Urina de Xarope de Bordo/genética , Doença da Urina de Xarope de Bordo/urina
8.
Anal Chim Acta ; 1058: 80-88, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-30851856

RESUMO

Herein, graphite nanosheets (GN) were first prepared through simple liquid-phase exfoliation of graphite powder in N, N-dimethylacetamide (DMAC). After then, ultrasmall Cu-based metal organic frame (HKUST-1) nanoparticles (less than 5 nm) were in-situ anchored on the surface of graphite nanosheets with high degree of dispersion. Due to the intrinsic structural advantages of the as-synthesized HKUST-1 nanoparticles decorated graphite nanosheets (HKUST-1/GN) hybrids, including superior electron transfer ability and the greatly enhanced adsorption property, HKUST-1/GN shows excellent electrochemical sensing performance toward DNA damage biomarker 8-hydroxy-2'-deoxyguanosine with fast detection speed (∼240 s), wide linear window (10 nM-1 µM), high sensitivity (346857 µA mM-1 cm-2), low detection limit (∼2.5 nM), and good reproducibility. As a result, a highly sensitive electrochemical sensing platform for the detection of DNA damage biomarker 8-hydroxy-2'-deoxyguanosine was fabricated basing the as-prepared HKUST-1/GN hybrids. What is more, the developed electrochemical method was successfully used for the detection of real samples and exhibited satisfied result.


Assuntos
Dano ao DNA , Desoxiguanosina/análogos & derivados , Técnicas Eletroquímicas/métodos , Grafite/química , Estruturas Metalorgânicas/química , Nanopartículas/química , Biomarcadores/urina , Cobre/química , Desoxiguanosina/urina , Humanos , Limite de Detecção , Tamanho da Partícula , Reprodutibilidade dos Testes
9.
PLoS One ; 14(2): e0212499, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30768632

RESUMO

BACKGROUND: It remains unclear whether daily physical activity is associated with DNA damage. This cross-sectional study examined the association between leisure-time physical activity and urinary 8-hydroxydeoxyguanosine (8-OH-dG), a biomarker of oxidative DNA damage, or urinary 7-methylguanine (m7Gua), a biomarker of methylating DNA damage. METHODS: Participants included 501 workers (294 men and 207 women), aged 20-65 years, from municipal offices in Japan. Urinary 8-OH-dG and m7Gua were measured using column-switching HPLC. Physical activity was evaluated using a self-reported questionnaire. The associations between leisure-time physical activity and urinary DNA damage markers were assessed by multiple linear regression analysis, with stratification by occupational physical activity. RESULTS: After adjusting for covariates, leisure-time physical activity showed a suggestive inverse correlation with urinary 8-OH-dG levels (P for trend = 0.06), and a significant inverse association with urinary m7Gua levels (P for trend = 0.03). In analysis stratified by occupation, inverse correlations were observed in sedentary workers (walking < 30 min/day at work: P for trend = 0.06 and = 0.03 for urinary 8-OH-dG and m7Gua, respectively), but not in physically active workers (walking ≥ 30 min/day at work). In analysis for each intensity of leisure-time physical activity, light-intensity exercise was associated with lower levels of urinary 8-OH-dG (P for trend = 0.03), whereas moderate-to-high-intensity exercise was associated with lower levels of urinary m7Gua (P for trend = 0.02). CONCLUSIONS: Our results suggest that high levels of leisure-time physical activity are associated with decreased levels of DNA damage in individuals with low physical activity at work.


Assuntos
Dano ao DNA , Exercício Físico , Atividades de Lazer , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Biomarcadores/urina , Estudos Transversais , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Feminino , Guanina/análogos & derivados , Guanina/urina , Humanos , Japão , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Ocupações , Adulto Jovem
10.
Environ Int ; 126: 153-161, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30798196

RESUMO

Human exposure to phthalates is ubiquitous and has received considerable attention due to their association with adverse health outcomes, including type 2 diabetes mellitus (T2DM). Nevertheless, earlier studies that link phthalate exposure to T2DM yielded ambiguous results. Furthermore, studies that associate phthalate exposure with oxidative stress and then with T2DM are scant. In this diabetic case-control study, urine samples collected from 101 individuals aged 28-68 years from Jeddah, Saudi Arabia, were analyzed to determine 20 phthalate metabolites (PhMs) and seven oxidative stress biomarkers (OSBs). Unconditional logistic regression was used to estimate odds ratios for the association between diabetes and urinary PhMs and OSBs in participants, stratified by age, gender, nationality, smoking status, occupation, and urinary creatinine. Twelve PhMs and five OSBs were found at detection rates above 50%, with geometric mean concentrations of 0.61-100 and 0.35-10.7 ng/mL (1.04-171 and 0.61-18.6 µg/g creatinine), respectively. Almost all exposures were significantly higher in diabetic cases than in controls. The 12 PhMs were positively associated with higher urinary concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin F2α (8-PGF2α). Individuals in the 3rd and/or 4th quartile(s) for urinary concentrations of PhMs and OSBs showed 3.7- and 7.3-fold increase, respectively, in the odds of having diabetes compared with those in the 1st quartile. The rank order of association of PhMs/OSBs with diabetes followed the order of: mEP ≈ mBP > mEHP > mCPP > mECPP ≈ mEOHP ≈ mEHHP ≈ mIBP ≈ mMP > mCMHP ≈ mBzP and 8-OHdG > 8-PGF2α ≈ 15-PGF2α. The relationship between phthalate exposure and risk of developing T2DM was mediated in part by phthalate-induced oxidative stress, especially 8-OHdG. Our study suggests that human exposure to phthalates is associated with increased oxidative stress which mediates the development of T2DM.


Assuntos
Diabetes Mellitus Tipo 2/urina , Poluentes Ambientais/urina , Estresse Oxidativo , Ácidos Ftálicos/urina , Adulto , Idoso , Biomarcadores/urina , Estudos de Casos e Controles , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Dinoprosta/análogos & derivados , Dinoprosta/urina , Monitoramento Ambiental , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Arábia Saudita/epidemiologia
11.
Environ Int ; 126: 184-192, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30798199

RESUMO

Prostatic enlargement might affect up to 30% of men and can cause signs and symptoms in the lower urinary tract in the elderly. Imbalanced estrogen and androgen secretions are important in prostatic physiopathology. Phthalates-environmental endocrine disruptors-affect androgen secretion and disrupt sexual organs, including testes and the prostate, but the underlying mechanisms are unclear. Using European Association of Urology (EAU) guidelines, we recruited from urology clinics in southern Taiwan 207 elderly men diagnosed with benign prostatic hyperplasia (BPH) and prostatic enlargement between 2015 and 2017. We took blood and urine samples from all patients on the same day. We used multivariate linear regression, associations, and potential interactions after we had measured and analyzed oxidative stress (OS) markers, steroidal hormones, and 11 urinary phthalate metabolites, and then we adjusted for confounders. Di(2-ethylhexyl) phthalate (DEHP) metabolite levels, particularly urinary mono-(2-ethylhexyl) phthalate, were positively associated with androgen, estrogen, hormone ratios, inducible nitric oxide synthetase (iNOS), 8-hydroxy-2'-deoxyguanosine (8-OHdG), prostate specific antigen (PSA), and prostate volume (PV) (p < 0.05). PV and PSA were positively associated with androgen, estrogen, hormone ratios and OS markers (p < 0.05). The estimated percentages of exposure to phthalates in prostatic enlargement mediated by androgen, estrogen, and OS markers ranged from 3.5% to 63.1%. Exposure to DEHP promoted the progress of BPH by increasing dihydrotestosterone (DHT), estradiol (E2), the converted enzymes aromatase and 5α reductase, and reactive oxygen species (ROS) (8-OHdG and iNOS) production. Sex hormones and OS might be important hyperplasia-promoters after a patient has been exposed to phthalates, especially to DEHP.


Assuntos
Disruptores Endócrinos/urina , Poluentes Ambientais/urina , Hormônios Esteroides Gonadais/sangue , Estresse Oxidativo , Ácidos Ftálicos/urina , Hiperplasia Prostática/sangue , Hiperplasia Prostática/urina , Androgênios/sangue , Biomarcadores/sangue , Biomarcadores/urina , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Estrogênios/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo II/sangue , Taiwan
12.
Metabolism ; 91: 53-60, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30513280

RESUMO

OBJECTIVE: Association of oxidative DNA damage with gain in anthropometric indices has not been fully elucidated. METHODS: In this study, participants (n = 1151) were derived from the baseline visit of Wuhan residents in the Wuhan-Zhuhai Cohort Study. The participants finished the physical examinations at both baseline and 3-year follow up. Urinary levels of 8-hydroxydeoxyguanosine (8-OHdG) were measured by gradient-elution high performance liquid chromatography method and then calibrated by urinary creatinine (Cr) values. RESULTS: Generalized linear models showed that after adjusted for confounding factors, baseline central obesity individuals with a ≥2.5% hip circumference (HC) loss or >5% HC gain had a 0.290 µmol/mol Cr (95% confidence interval (CI): 0.108, 0.472) or 0.553 µmol/mol Cr (95% CI: 0.273, 0.833) increase in urinary 8-OHdG levels compared with those with a -2.5%-2.5% HC gain (both P < 0.05). Moreover, compared with non-central obesity at both baseline and 3-year follow-up, we observed that central obese men at both baseline and 3-year follow-up had a 0.46 µmol/mol Cr (95% CI: 0.16, 0.75) increased in urinary 8-OHdG levels. CONCLUSIONS: HC gain showed dose-dependent associations with urinary 8-OHdG levels. Moreover, male central obesity at both baseline and 3-year follow-up had an increased risk for urinary 8-OHdG levels.


Assuntos
Desoxiguanosina/análogos & derivados , Obesidade Abdominal/urina , Adulto , Idoso , Antropometria , Pressão Sanguínea , Estudos de Coortes , Creatinina/urina , Desoxiguanosina/urina , Feminino , Seguimentos , Humanos , Estilo de Vida , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Circunferência da Cintura
13.
Redox Biol ; 20: 556-565, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30508700

RESUMO

A reliable and fast liquid chromatography-tandem mass spectrometry method has been developed for the simultaneous determination of three oxidized nucleic acid damage products in urine, 8-oxoguanine (8-oxoGua), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo). We applied this method to assess the effect of various urine workup procedures on the urinary concentrations of the oxidized nucleic acid products. Our results showed that frozen urine samples must be warmed (i.e., to 37 °C) to re-dissolve any precipitates prior to analysis. We showed that common workup procedures, such as thawing at room temperature or dilution with deionized water, are not capable of releasing fully the oxidized nucleic acid products from the precipitates, and result in significant underestimation (up to ~ 100% for 8-oxoGua, ~ 86% for both 8-oxodGuo and 8-oxoGuo). With this method, we further assessed and compared the ability of the three oxidized nucleic acid products, as well as malondialdehyde (MDA, a product of lipid peroxidation), to biomonitor oxidative stress in vivo. We measured a total of 315 urine samples from subjects with burdens of oxidative stress from low to high, including healthy subjects, patients with chronic obstructive pulmonary disease (COPD), and patients on mechanical ventilation (MV). The results showed that both the MV and COPD patients had significantly higher urinary levels of 8-oxoGua, 8-oxodGuo, and 8-oxoGuo (P < 0.001), but lower MDA levels, compared to healthy controls. Receiver operating characteristic curve analysis revealed that urinary 8-oxoGuo is the most sensitive biomarker for oxidative stress with area under the curve (AUC) of 0.91, followed by 8-oxodGuo (AUC: 0.80) and 8-oxoGua (AUC: 0.76). Interestingly, MDA with AUC of 0.34 failed to discriminate the patients from healthy controls. Emerging evidence suggests a potential clinical utility for the measurement of urinary 8-oxoGuo, and to a lesser extent 8-oxodGuo, which is strongly supported by our findings.


Assuntos
Biomarcadores/urina , Guanina/metabolismo , Estresse Oxidativo , Idoso , Cromatografia Líquida , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Feminino , Guanina/análogos & derivados , Guanina/urina , Guanosina/análogos & derivados , Guanosina/urina , Humanos , Masculino , Metaboloma , Metabolômica , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/urina , Curva ROC , Espécies Reativas de Oxigênio/urina , Espectrometria de Massas em Tandem , Temperatura
14.
Acta Trop ; 189: 124-128, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30321522

RESUMO

Inflammation of the hepatobiliary system in chronic opisthorchiasis is associated with an elevated level of urinary 8-oxo-7,8 dihydro-2'deoxyguanosine (8-oxodG) during active as well as past exposure to Opisthorchis viverrini infection. In this study, we evaluated the short-term effect of praziquantel treatment on hepatobiliary disease (HBD) using urinary 8-oxodG as an inflammatory marker in a cohort of residents in endemic areas of opisthorchiasis in Khon Kaen, Thailand. The HBD status in terms of periductal fibrosis (PDF) was determined by abdominal ultrasonography and O. viverrini infection was monitored at baseline and 2-4 weeks after curative treatment by praziquantel. Analysis of O. viverrini-infected participants who were PDF-ve revealed that there was a significant reduction of urinary 8-oxodG after treatment compared with the baseline levels (p < 0.001). By contrast, in PDF+ve individuals, the levels of urinary 8-oxodG were similar between baseline and those post-treatment. Although confirmation by using a larger sample size is needed, the positive association between HBD and urinary 8-oxodG level after worm clearance suggests that chronic hepatobiliary inflammation is neither affected nor interrupted by short-term praziquantel treatment. Individuals with persistent PDF at pre- and post-treatment who have a high risk of cholangiocarcinoma, could be identified within 2-4 weeks after parasite removal by drug treatment. Thus, urinary 8-oxodG is a useful biomarker for predicting persistent PDF in individuals with a recent drug treatment history who require further clinical investigation, management and treatment.


Assuntos
Anti-Helmínticos/farmacologia , Desoxiguanosina/análogos & derivados , Opistorquíase/tratamento farmacológico , Praziquantel/farmacologia , Animais , Doenças Biliares/parasitologia , Biomarcadores/urina , Desoxiguanosina/urina , Feminino , Humanos , Hepatopatias/parasitologia , Masculino , Pessoa de Meia-Idade , Opistorquíase/complicações
15.
Environ Int ; 123: 171-180, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30529889

RESUMO

INTRODUCTION: Few studies have investigated the role of exposure to metals and metal mixtures on oxidative stress in the general population. OBJECTIVES: We evaluated the cross-sectional association of urinary metal and metal mixtures with urinary oxidative stress biomarkers, including oxidized to reduced glutathione ratio (GSSG/GSH), malondialdehyde (MDA), and 8­oxo­7,8­dihydroguanine (8-oxo-dG), in a representative sample of a general population from Spain (Hortega Study). METHODS: Urine antimony (Sb), barium (Ba), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), molybdenum (Mo), vanadium (V) and zinc (Zn) were measured by ICPMS in 1440 Hortega Study participants. RESULTS: The geometric mean ratios (GMRs) of GSSG/GSH comparing the 80th to the 20th percentiles of metal distributions were 1.15 (95% confidence intervals [95% CI]: 1.03-1.27) for Mo, 1.17 (1.05-1.31) for Ba, 1.23 (1.04-1.46) for Cr and 1.18 (1.00-1.40) for V. For MDA, the corresponding GMRs (95% CI) were 1.13 (1.03-1.24) for Zn and 1.12 (1.02-1.23) for Cd. In 8-oxo-dG models, the corresponding GMR (95% CI) were 1.12 (1.01-1.23) for Zn and 1.09 (0.99-1.20) for Cd. Cr for GSSG/GSH and Zn for MDA and 8-oxo-dG drove most of the observed associations. Principal component (PC) 1 (largely reflecting non-essential metals) was positively associated with GSSG/GSH. The association of PC2 (largely reflecting essential metals) was positive for GSSG/GSH but inverse for MDA. CONCLUSIONS: Urine Ba, Cd, Cr, Mo, V and Zn were positively associated with oxidative stress measures at metal exposure levels relevant for the general population. The potential health consequences of environmental, including nutritional, exposure to these metals warrants further investigation.


Assuntos
Poluentes Ambientais/urina , Metais Pesados/urina , Estresse Oxidativo , Adulto , Idoso , Biomarcadores/urina , Estudos Transversais , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Feminino , Glutationa/urina , Humanos , Masculino , Malondialdeído/urina , Pessoa de Meia-Idade , Espanha
16.
Environ Int ; 123: 382-389, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30572170

RESUMO

Oxidative stress in humans is affected by the health and nutritional status as well as exposure to external environmental factors. To evaluate the effects of external factors, an assessment of baseline levels as well as diurnal variations in oxidative stress status of healthy individuals is needed. In this study, we examined intra- and inter-individual variability of oxidative stress biomarkers (OSBs) of lipids (malondialdehyde [MDA] and four F2-isoprostane isomers, namely, 8-isoprostaglandinF2α [8-PGF2α], 11ß-prostaglandinF2α [11-PGF2α], 15(R)-prostaglandinF2α [15-PGF2α], and 8-iso,15(R)-prostaglandinF2α [8,15-PGF2α]); proteins (o,o'-dityrosine [diY]); and DNA (8-hydroxy-2'-deoxyguanosine [8-OHdG]) in urine from healthy individuals. The significance of creatinine correction, which is typically used to account for urinary dilution, on OSB concentrations was evaluated. Analysis of 515 urine samples, collected longitudinally from 19 healthy individuals daily for over a month, showed inter-individual coefficient of variation (CV) in concentrations from 112% for MDA to 272% for 15-PGF2α. Intra-individual CV in concentrations ranged from 29% for 8-OHdG to 149% for 15-PGF2α. MDA was the most abundant OSB found in urine. The intra- and inter-individual variability in F2-isoprostane concentrations were higher than the values calculated for diY, 8-OHdG, and MDA. All seven OSB concentrations were significantly correlated with each other and with creatinine. Creatinine normalization of OSB concentrations improved predictability in OSB concentrations over time. Our results suggest that 8-OHdG, showing the highest ICC (0.96), yielded more reproducible measurements with a low CV, and is the most suitable biomarker of OSB in spot urine samples. The measured concentrations and diurnal variability in urinary OSB levels in healthy individuals reported in this study are useful as a benchmark for future toxicological and epidemiological studies.


Assuntos
Biomarcadores/urina , Estresse Oxidativo , Creatinina/urina , DNA , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Feminino , Voluntários Saudáveis , Humanos , Lipídeos , Masculino , Malondialdeído/urina , Estado Nutricional , Oxirredução , Valores de Referência , Tirosina/análogos & derivados , Tirosina/urina
17.
Anal Chim Acta ; 1047: 9-20, 2019 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-30567668

RESUMO

In this work, carbon quantum dots (CQD) encapsulated in super small platinum nanocrystals core-shell architecture/nitrogen doped graphene hybrid nanocomposite (CQD@PDA@PtNCs-NGR) was design synthesized. Without using any capping reagent, stabilizer and surfactant, very small CQD was served as template and anchoring point for the synthesis of Pt NCs with a super small size (2.25 nm) and a uniform distribution. Meanwhile, dopamine (DA) was used as bridging agent, positioning agent and weak reducing agent to make Pt2+ grow on the CQD. Combine the high dispersed Pt NCs with high specific surface area and high conductivity of NGR, the CQD@PDA@PtNCs-NGR shows excellent electrocatalytic performance towards the biosensing of DNA damage biomarker- 8-Hydroxy-2'-deoxyguanosine (8-OH-dG). A very low detection limit of 0.45 nM and 0.85 nM (S/N = 3), a wide linear range of 0.013 µM-109.78 µM and a high sensitivity of 7.912 µA µM-1cm-2 and 4.190 µA µM-1cm-2 were obtained. The fabricated CQD@PDA@PtNCs-NGR realized the detection of 8-OH-dG in human urine practical sample. Furthermore, CQD@PDA@PtNCs-NGR was applied for the determination of 8-OH-dG generated from damaged DNA and damaged guanine (G), respectively. This work effectively combines the electrochemical signal of 8-OH-dG with DNA damage, confirms the mechanism of DNA damage, which might pave a new way to establish the associations between degree of DNA damage and 8-OH-dG.


Assuntos
DNA/química , Desoxiguanosina/análogos & derivados , Grafite/química , Nanocompostos/química , Platina/química , Pontos Quânticos/química , Técnicas Biossensoriais/métodos , Dano ao DNA , Desoxiguanosina/urina , Técnicas Eletroquímicas/métodos , Concentração de Íons de Hidrogênio , Indóis/química , Limite de Detecção , Tamanho da Partícula , Polímeros/química
18.
Environ Int ; 123: 301-309, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30553203

RESUMO

BACKGROUND: Bisphenol F (BPF) and bisphenol S (BPS) are increasingly used as alternatives to endocrine disrupting chemical bisphenol A (BPA). Evidence from in vitro and animal studies demonstrates that BPA, BPF and BPS induce oxidative stress, a proposed mechanism that is relevant to various adverse health effects. Evaluation in humans is hampered by the potentially high within-subject variability of urinary measurements. OBJECTIVE: To evaluate the variability and associations of levels of BPA, BPS, BPF and 3 oxidative stress markers [i.e., 8-hydroxy-2-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)] in urine collected on multiple occasions over 3 months. METHOD: A total of 529 spot urine samples, including 88 first morning voids (FMVs) and 24-h specimens, were gathered from 11 adult men on days 0, 1, 2, 3, 4, 30, 60 and 90 and analyzed for BPA, BPF, BPS, 8-OHdG, 8-isoPGF2α and HNE-MA. Intraclass correlation coefficients (ICCs) were estimated to characterize the reproducibility of urinary bisphenols and oxidative stress markers, and linear mixed models were applied to assess the associations between markers of exposure and response. RESULTS: BPA and BPF were detected in ≥85% of the spot samples, while BPS in 13% of the samples. High degrees of within-subject variability were found for BPA, BPF, 8-OHdG, 8-isoPGF2α and HNE-MA in spot samples, FMVs and 24-h specimens (creatinine-corrected ICCs ≤ 0.37). The sensitivities were low-to-moderate (0.30-0.63) when using single spot samples or FMVs to predict high (>27th, or 36th percentile) 3-month average urinary levels of BPA, BPF, 8-OHdG, 8-isoPGF2α and HNE-MA. Collecting repeated specimens at different time points improved the accuracy of classification for markers of exposure and response. Elevated urinary BPA and BPF were associated with significantly higher levels of oxidative stress markers. CONCLUSIONS: Repeated urinary specimens are required to characterize bisphenol exposure levels and the oxidative stress status of individuals. Exposure to BPA and BPF may partly contribute to the elevated urinary levels of oxidative stress makers in adult men.


Assuntos
Compostos Benzidrílicos/urina , Estresse Oxidativo , Fenóis/urina , Sulfonas/urina , Adulto , Animais , Variação Biológica Individual , Biomarcadores/urina , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Humanos , Masculino , Reprodutibilidade dos Testes
19.
Sci Rep ; 8(1): 17926, 2018 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-30560943

RESUMO

In sleep apnea syndrome (SAS), chronic intermittent hypoxia (CIH) is believed to activate the sympathetic nerve system, and is thus involved in cardiovascular diseases (CVD). However, since patients with SAS are often already obese, and have diabetes and/or hypertension (HT), the effects of CIH alone on sympathetic nerve activation and its impacts on CVD are largely unknown. We, therefore, examined the effects of CIH on sympathetic nerve activation in non-obese mice to determine whether renal sympathetic nerve denervation (RD) could ameliorate CIH-mediated cardiovascular effects. Male C57BL/6 (WT) mice were exposed to normal (FiO2 21%) or CIH (10% O2, 12 times/h, 8 h/day) conditions for 4 weeks with or without RD treatment. Increased urinary norepinephrine (NE), 8-OHdG, and angiotensinogen levels and elevated serum asymmetric dimethyl arginine levels were observed in the CIH model. Concomitant with these changes, blood pressure levels were significantly elevated by CIH treatment. However, these deleterious effects by CIH were completely blocked by RD treatment. The present study demonstrated that CIH-mediated renal sympathetic nerve activation is involved in increased systemic oxidative stress, endothelial dysfunction, and renin-angiotensin system activation, thereby contributing to the development of HT and CVD, thus could be an important therapeutic target in patients with SAS.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Hipertensão/prevenção & controle , Hipóxia/complicações , Simpatectomia/métodos , Sistema Nervoso Simpático/cirurgia , Angiotensinas/urina , Animais , Arginina/análogos & derivados , Arginina/sangue , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Modelos Animais de Doenças , Humanos , Hipóxia/sangue , Hipóxia/urina , Rim/inervação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Norepinefrina/urina , Estresse Oxidativo
20.
Biomed Res ; 39(6): 269-277, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30531156

RESUMO

Pelvic venous congestion (PC) is thought to be related to several diseases of the lower urinary tract (LUT). We examined the characteristics of the LUT in rats with PC. To create PC, female rats were anesthetized with isoflurane, and the bilateral common iliac veins and bilateral uterine veins were ligated. At 1-8 weeks after either ligation or sham surgery, we performed cystometry with or without administration of carbazochrome sodium sulfonate hydrate or propiverine hydrochloride, histologic examination of the bladder, blood flow imaging, assessment of locomotor activity, measurement of urinary 8-hydroxydeoxyguanosine (8-OHdG) and nitric oxide metabolites (NOx), and the Evans blue dye extravasation test. PC elevated frequency of urination after 2-6 weeks, and caused a decrease of spontaneous locomotor activity. In addition, there was a decrease of bladder blood flow, an increase of bladder vascular permeability, an increase of urinary 8-OHdG, a decrease of urinary NOx, and mild inflammatory changes of the bladder. In rats with PC, frequency of urination was normalized by administration of propiverine or carbazochrome. Rats with PC may be used as a model of PC associated with high frequency of urination, and this model may be useful when developing treatment for LUT symptoms associated with PC.


Assuntos
Hiperemia/fisiopatologia , Bexiga Urinária/fisiopatologia , Doenças Urológicas/fisiopatologia , Adrenocromo/análogos & derivados , Adrenocromo/farmacologia , Animais , Benzilatos/farmacologia , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Modelos Animais de Doenças , Feminino , Locomoção , Óxido Nítrico/urina , Ratos , Ratos Sprague-Dawley , Micção/efeitos dos fármacos
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