Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 164
Filtrar
1.
Mutagenesis ; 38(4): 216-226, 2023 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-37422797

RESUMO

Post-COVID conditions are defined as the continuation of the symptoms of Coronavirus Disease 2019 (COVID-19) 3 months after the initial Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, with no other explanation. Post-COVID conditions are seen among 30%-60% of patients with asymptomatic or mild forms of COVID-19. The underlying pathophysiological mechanisms of post-COVID conditions are not known. In SARS-CoV-2 infection, activation of the immune system leads to increased production of reactive oxygen molecules, depleted antioxidant reserve, and finally occurrence of oxidative stress. In oxidative stress conditions, DNA damage increases and DNA repair systems impair. In this study, glutathione (GSH) level, glutathione peroxidase (GPx) activity, 8-hydroxydeoxyguanosine (8-OHdG) level, basal, induced, and post-repair DNA damage were investigated in individuals suffering from post-COVID conditions. In the red blood cells, GSH levels and GPx activities were measured with a spectrophotometric assay and a commercial kit. Basal, in vitro H2O2 (hydrogen peroxide)-induced, and post-repair DNA damage (DNA damage after a repair incubation following H2O2-treatment, in vitro) were determined in lymphocytes by the comet assay. The urinary 8-OHdG levels were measured by using a commercial ELISA kit. No significant difference was found between the patient and control groups for GSH level, GPx activity, and basal and H2O2-induced DNA damage. Post-repair DNA damage was found to be higher in the patient group than those in the control group. Urinary 8-OHdG level was lower in the patient group compared to the control group. In the control group, GSH level and post-repair DNA damage were higher in the vaccinated individuals. In conclusion, oxidative stress formed due to the immune response against SARS-COV-2 may impair DNA repair mechanisms. Defective DNA repair may be an underlying pathological mechanism of post-COVID conditions.


Assuntos
Antioxidantes , COVID-19 , Humanos , Antioxidantes/metabolismo , Peróxido de Hidrogênio/farmacologia , Síndrome de COVID-19 Pós-Aguda , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , SARS-CoV-2/metabolismo , Dano ao DNA , Reparo do DNA , Glutationa/metabolismo , Estresse Oxidativo , 8-Hidroxi-2'-Desoxiguanosina
2.
Pharmacol Res ; 192: 106786, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37146924

RESUMO

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of disease phenotypes which start with simple steatosis and lipid accumulation in the hepatocytes - a typical histological lesions characteristic. It may progress to non-alcoholic steatohepatitis (NASH) that is characterized by hepatic inflammation and/or fibrosis and subsequent onset of NAFLD-related cirrhosis and hepatocellular carcinoma (HCC). Due to the central role of the liver in metabolism, NAFLD is regarded as a result of and contribution to the metabolic abnormalities seen in the metabolic syndrome. Peroxisome proliferator-activated receptors (PPARs) has three subtypes, which govern the expression of genes responsible for energy metabolism, cellular development, inflammation, and differentiation. The agonists of PPARα, such as fenofibrate and clofibrate, have been used as lipid-lowering drugs in clinical practice. Thiazolidinediones (TZDs) - ligands of PPARγ, such as rosiglitazone and pioglitazone, are also used in the treatment of type 2 diabetes (T2D) with insulin resistance (IR). Increasing evidence suggests that PPARß/δ agonists have potential therapeutic effects in improving insulin sensitivity and lipid metabolism disorders. In addition, PPARs ligands have been considered as potential therapeutic drugs for hypertension, atherosclerosis (AS) or diabetic nephropathy. Their crucial biological roles dictate the significance of PPARs-targeting in medical research and drug discovery. Here, it reviews the biological activities, ligand selectivity and biological functions of the PPARs family, and discusses the relationship between PPARs and the pathogenesis of NAFLD and metabolic syndrome. This will open new possibilities for PPARs application in medicine, and provide a new idea for the treatment of fatty liver and related diseases.


Assuntos
Carcinoma Hepatocelular , Diabetes Mellitus Tipo 2 , Neoplasias Hepáticas , Síndrome Metabólica , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Síndrome Metabólica/metabolismo , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Fígado/metabolismo , PPAR alfa/metabolismo , Inflamação/metabolismo , Lipídeos/uso terapêutico
3.
BMC Neurol ; 22(1): 21, 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35016629

RESUMO

BACKGROUND: Immersive virtual reality (VR)-based motor control training (VRT) is an innovative approach to improve motor function in patients with stroke. Currently, outcome measures for immersive VRT mainly focus on motor function. However, serum biomarkers help detect precise and subtle physiological changes. Therefore, this study aimed to identify the effects of immersive VRT on inflammation, oxidative stress, neuroplasticity and upper limb motor function in stroke patients. METHODS: Thirty patients with chronic stroke were randomized to the VRT or conventional occupational therapy (COT) groups. Serum biomarkers including interleukin 6 (IL-6), intracellular adhesion molecule 1 (ICAM-1), heme oxygenase 1 (HO-1), 8-hydroxy-2-deoxyguanosine (8-OHdG), and brain-derived neurotrophic factor (BDNF) were assessed to reflect inflammation, oxidative stress and neuroplasticity. Clinical assessments including active range of motion of the upper limb and the Fugl-Meyer Assessment for upper extremity (FMA-UE) were also used. Two-way mixed analyses of variance (ANOVAs) were used to examine the effects of the intervention (VRT and COT) and time on serum biomarkers and upper limb motor function. RESULTS: We found significant time effects in serum IL-6 (p = 0.010), HO-1 (p = 0.002), 8-OHdG (p = 0.045), and all items/subscales of the clinical assessments (ps < 0.05), except FMA-UE-Coordination/Speed (p = 0.055). However, significant group effects existed only in items of the AROM-Elbow Extension (p = 0.007) and AROM-Forearm Pronation (p = 0.048). Moreover, significant interactions between time and group existed in item/subscales of FMA-UE-Shoulder/Elbow/Forearm (p = 0.004), FMA-UE-Total score (p = 0.008), and AROM-Shoulder Flexion (p = 0.001). CONCLUSION: This was the first study to combine the effectiveness of immersive VRT using serum biomarkers as outcome measures. Our study demonstrated promising results that support the further application of commercial and immersive VR technologies in patients with chronic stroke.


Assuntos
Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Realidade Virtual , Humanos , Inflamação , Plasticidade Neuronal , Estresse Oxidativo , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/terapia , Resultado do Tratamento , Extremidade Superior
4.
Molecules ; 27(13)2022 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-35807276

RESUMO

The aim of this study is to examine the ability of resveratrol to counteract hexavalent chromium [Cr(VI)]-induced genetic damage, as well as the possible pathways associated with this protection. Hsd:ICR male mice are divided into groups of the following five individuals each: (a) control 1, distilled water; (b) control 2, ethanol 30%; (c) resveratrol, 50 mg/kg by gavage; (d) CrO3, 20 mg/kg intraperitoneally; (e) resveratrol + CrO3, resveratrol administered 4 h prior to CrO3. The assessment is performed on peripheral blood. Micronuclei (MN) kinetics are measured from 0 to 72 h, while 8-hydroxydeoxyguanosine (8-OHdG) adduct repair levels, endogenous antioxidant system biomarkers, and apoptosis frequency were quantified after 48 h. Resveratrol reduces the frequency of Cr(VI)-induced MN and shows significant effects on the 8-OHdG adduct levels, suggesting that cell repair could be enhanced by this polyphenol. Concomitant administration of resveratrol and Cr(VI) results in a return of the activities of glutathione peroxidase and catalase to control levels, accompanied by modifications of superoxide dismutase activity and glutathione levels. Thus, antioxidant properties might play an important role in resveratrol-mediated inhibition of Cr(VI)-induced oxidant genotoxicity. The increase in apoptotic cells and the decrease in necrosis further confirmed that resveratrol effectively blocks the actions of Cr(VI).


Assuntos
Cromo , Dano ao DNA , 8-Hidroxi-2'-Desoxiguanosina , Animais , Antioxidantes/farmacologia , Cromo/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos ICR , Resveratrol/farmacologia
5.
J Obstet Gynaecol ; 42(2): 338-345, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34159896

RESUMO

This study aimed to determine the effect of 3',4'-Dihydroxyflavonol (DiOHF) on lipid peroxidation, DNA damage and inflammation in ovarian ischaemia (I)-reperfusion (R) injury. This study was performed on 44 Wistar-albino female rats. Groups were designed as Control; Sham; I/R (the left ovary was ligated for 2 h and then reperfused for 2 h); I/R + DiOHF (after 2 h ischaemia and 2 h reperfusion, 30 mg/kg of DiOHF was given intraperitoneally and reperfusion was allowed for 2 h more); I + DiOHF + R (after 2 h I, 30 mg/kg of DiOHF was given at the beginning of 2 h reperfusion); DiOHF + I/R (2 h after DiOHF administration, the left ovary was ligated for 2 h and then reperfused for 2 h). Blood and ovarian tissue samples were analysed for GSH, MDA, 8-OHdG, SOD, and IL-6. Ovarian tissue was examined histopathologically. Ovarian I/R has led to inflammation and oxidative damage. However, DiOHF activated the antioxidant system and prevented DNA damage induced by I/R in ovarian tissue. Vascularisation, oedema, and inflammation also occurred in ovarian tissue in I/R group. The results of this study indicated that I/R led to disturbance of the oxidant/antioxidant system balance and increased DNA damage; however, DiOHF supplementation prevented DNA damage, lipid peroxidation and inflammation by increasing the antioxidant system in ovarian I/R injury in rats. However, in potential I/R situations, DiOHF application appears to be beneficial in reducing inflammation, oxidant injury, and DNA damage, and in activating the antioxidant system. IMPACT STATEMENTWhat is already known on this subject? Ischaemia/reperfusion (I/R) injuries lead to damage in cells or tissues due to insufficient blood flow.What do the results of this study add? Increased DNA injury and inflammatory response (IL-6) and structural impairment were treated by administration of intraperitoneal (DiOHF) which strongly stimulated the antioxidant system, inhibited antioxidant activities, prevented DNA damage and inflammation process.What are the implications of these findings for clinical practice and/or further research? This study's strength is that it is the first research demonstrates the prevention of DNA damage in ovarian I/R by DiOHF supplementation. This flavonoid (DiOHF) may be used for treatment in different ovarian ischaemia/reperfusion.


Assuntos
Ovário , Traumatismo por Reperfusão , Animais , Dano ao DNA , Feminino , Flavonóis , Inflamação/prevenção & controle , Peroxidação de Lipídeos , Malondialdeído , Ratos , Ratos Wistar , Traumatismo por Reperfusão/prevenção & controle
6.
Heart Vessels ; 36(1): 38-47, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32632553

RESUMO

The aim of the present study was to determine whether urinary 8-hydroxydeoxyguanosine (8-OHdG), which is a marker of oxidative stress, can predict future cardiovascular death in patients with acute coronary syndrome (ACS). A total of 551 consecutive patients with ACS who underwent admission urinary 8-OHdG measurements were enrolled in this study. The patients were divided into 2 groups according to the optimal cutoff value of admission urinary 8-OHdG determined by a receiver-operating characteristics curve for the prediction of cardiovascular death: a high admission urinary 8-OHdG group, 169 patients with admission urinary 8-OHdG ≥ 17.92 ng/mg creatinine; and a low admission urinary 8-OHdG group, 382 patients with admission urinary 8-OHdG < 17.92 ng/mg creatinine. The patients were followed up for a median period of 34 months. The primary and secondary end points were the incidence of cardiovascular death and major cardiovascular events (MACE) composed of cardiovascular death, non-fatal myocardial infarction, or urgent hospitalization for heart failure. Of the 551 patients, cardiovascular deaths and MACE occurred in 14 (2.5%) and 35 (6.4%), respectively. The Kaplan-Meier estimate of the event-free rate revealed cardiovascular deaths and MACE were more likely in the high admission 8-OHdG group than in the low admission 8-OHdG group (log rank, both P < 0.001). Multiple adjusted Cox proportional hazards analysis indicated that high admission urinary 8-OHdG was an independent predictor of cardiovascular death (hazard ratio [HR] 7.642, P = 0.011) and MACE (HR 2.153, P = 0.049). High admission urinary 8-OHdG levels predict cardiovascular mortality after adjustment in patients with ACS.


Assuntos
8-Hidroxi-2'-Desoxiguanosina/análogos & derivados , Síndrome Coronariana Aguda/urina , Admissão do Paciente , Medição de Risco/métodos , 8-Hidroxi-2'-Desoxiguanosina/urina , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/mortalidade , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/urina , Ecocardiografia , Feminino , Seguimentos , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Curva ROC , Fatores de Risco , Taxa de Sobrevida/tendências
7.
J Toxicol Environ Health A ; 84(8): 331-344, 2021 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-33372577

RESUMO

This study aimed to investigate the relationship between endogenous antioxidant system, 8-hydroxydeoxyguanosine adduct (8-OHdG) repair, and apoptosis in mice treated with chromium(VI) alone and in the presence of the antigenotoxic compound (-)-epigallocatechin-3-gallate (EGCG). Groups of 5 Hsd:ICR male mice were divided and treated as follows: (1) control, vehicle only; (2) EGCG, 8.5 mg/kg by gavage alone; (3) CrO3, 20 mg/kg intraperitoneally alone; and (4) EGCG combined with CrO3, EGCG was administered 4 hr prior to CrO3. Peripheral blood parameters were analyzed before treatment administration (time 0), and 48 hr after exposure. The administration of EGCG increased 8-OHdG levels and superoxide dismutase (SOD) activity. Treatment with CrO3 increased number of micronucleus (MN) presence, elevated apoptotic/necrotic cells frequencies, decreased 8-OHdG levels, diminished total antioxidant capacity (TAC), increased glutathione (GSH) total levels, and lowered SOD activity. Administration of EGCG prior to treatment with CrO3 resulted in lower concentrations of MN, reduced apoptotic and necrotic cell number, and restored TAC and SOD activity to control levels. It is conceivable that the dose of EGCG plays an important role in the genotoxic damage protection pathways. Thus, this study confirms the action of EGCG as an antigenotoxic agent against chromium(VI)-induced oxidative insults and demonstrates potential protective pathways for EGCG actions to counteract genotoxic damage induced by this metal.


Assuntos
8-Hidroxi-2'-Desoxiguanosina/metabolismo , Antimutagênicos/farmacologia , Apoptose , Catequina/análogos & derivados , Cromo/efeitos adversos , Adutos de DNA/metabolismo , Poluentes Ambientais/efeitos adversos , Animais , Antioxidantes/metabolismo , Catequina/farmacologia , Masculino , Camundongos
8.
Environ Monit Assess ; 193(6): 342, 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-34002328

RESUMO

DPM (diesel particulate matter) is ubiquitously present in the mining environment and is known for mutagenicity and carcinogenicity to humans. However, its health effects in surface coal mines are not well studied, particularly in India. In this study, DPM exposure and corresponding exposure biomarkers were investigated in four different surface coal mines in Central India. To document and evaluate the DPM exposure in surface coal miners, we characterized 1-NP (1-nitropyrene) in the mining environment as surrogate for DPM using Sioutas Cascade Impactor. Exposure biomarkers were analyzed by collecting post work shift (8-h work shift) urine samples and determining the concentrations of 1-aminopyrene (1-AP) as a metabolite of 1-NP and 8-hydroxydeoxyguanosine (8OHdG) as DNA damage marker. We observed high concentration of 1-NP (7.13-52.46 ng/m3) in all the mines compared with the earlier reported values. The average creatinine corrected 1-AP and 8OHdG levels ranged 0.07-0.43 [Formula: see text]g/g and 32.47-64.16 [Formula: see text]g/g, respectively, in different mines. We found 1-AP in majority of the mine workers' urine (55.53%) and its level was higher than that reported for general environmental exposure in earlier studies. Thus, the study finding indicates occupational exposure to DPM in all the four mines. However, the association between 1-NP level and exposure biomarkers (1-AP and 8OHdG) was inconsistent, which may be due to individual physiological variations. The data on exposure levels in this study will help to understand the epidemiological risk assessment of DPM in surface coal miners. Further biomonitoring and cohort study are needed to exactly quantify the occupational health impacts caused by DPM among coal miners.


Assuntos
Poluentes Ocupacionais do Ar , Minas de Carvão , Mineradores , Exposição Ocupacional , Poluentes Ocupacionais do Ar/análise , Carvão Mineral , Estudos de Coortes , Monitoramento Ambiental , Humanos , Índia , Exposição Ocupacional/análise , Material Particulado/análise , Pirenos , Emissões de Veículos/análise
9.
Neurourol Urodyn ; 39(8): 2305-2313, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32813897

RESUMO

AIMS: In overactive bladder (OAB) research, different biomarkers have been proposed as diagnostic tools and may be used to create individual patient profiles. Assessing the diagnostic performance of biomarkers would better outline their utility. Therefore, our aim was to investigate the diagnostic value of four urinary biomarkers: human brain derived neurotrophic factor (hBDNF), malondialdehyde (MDA), h nerve growth factor (hNGF) and h 8-hydroxydeoxyguanosine in women with OAB. These are neurotrophins/oxidative stress markers that have been linked to lower urinary tract symptoms. METHODS: A total of 105 women were included in the study and distributed in two groups: a group with OAB (n = 53) and a control group (n = 50). The levels of the biomarkers were determined using enzyme-linked immunosorbent assay technique and they were compared between the groups. If the Mann-Whitney test demonstrated a statistically significant difference, receiver operating curves (ROC) analysis was undertaken. RESULTS: When normalized to urinary creatinine, hBDNF, MDA, and hNGF showed significantly increased values in women with OAB as compared to controls, whereas 8-OHdG showed no significant difference. The diagnostic performance of these biomarkers was analyzed based on the area under the ROC curve (AUC). MDA had the highest AUC (0.75), followed by hNGF (0.69) and hBDNF (0.67). CONCLUSIONS: Our findings suggest that MDA, a relatively novel biomarker in OAB research, has a fair performance as a diagnostic tool for OAB. Moreover, urinary neurotrophins (NGF and BDNF) as biomarkers may have a role in the diagnostic pathways of women with OAB symptoms.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/urina , Fator de Crescimento Neural/urina , Bexiga Urinária Hiperativa/diagnóstico , 8-Hidroxi-2'-Desoxiguanosina/urina , Adulto , Biomarcadores/urina , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Malondialdeído/urina , Pessoa de Meia-Idade , Urinálise , Bexiga Urinária Hiperativa/urina
10.
J Gastroenterol Hepatol ; 35(6): 1078-1087, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31907970

RESUMO

BACKGROUND AND AIM: Exogenous 8-hydroxydeoxyguanosine (8-OHdG) was suggested as an inhibitor of Rac1 and NADPH oxidase (NOX). The aim of this study was to evaluate the effects of the exogenous 8-OHdG on hepatic fibrogenesis in vitro and in vivo model of liver fibrosis. METHODS: Adult Sprague-Dawley rats were allocated to sham-operated rats (n = 7), rats that underwent bile duct ligation (BDL) (n = 6), and BDL rats treated with 8-OHdG (60 mg/kg/day by gavage, n = 6). All rats were sacrificed on day 21. Double immunofluorescence staining between either NOX1 or NOX2 and α-smooth muscle actin (SMA) in liver was performed. Hepatic fibrotic contents were assessed by hydroxyproline assay and quantified by Sirius red staining. In vitro, hepatic stellate cell (HSC) line LX-2 and HHSteC cells were stimulated by angiotensin II (10 µM). The reactive oxygen species (ROS) production was measured by confocal microscopy. The expressions of NOX1, NOX2, α-SMA, transforming growth factor (TGF)-ß1, and collagen Iα were analyzed by quantitative real-time polymerase chain reaction or immunoblotting. RESULTS: The 8-OHdG treatment in BDL rats reduced the NOX1 and NOX2 protein expression, which overlapped with α-SMA compared with BDL rats. The 8-OHdG treatment in BDL rats significantly decreased the mRNA expression of NOX1, NOX2, α-SMA, TGF-ß1, and collagen Iα, and fibrotic contents. Increases of ROS production, Rac1 activation, NOX1, NOX2, and fibronectin expression induced by angiotensin II in HSCs were attenuated by 8-OHdG. CONCLUSIONS: Rac1 activation and NOX-derived ROS are implicated to liver fibrosis. The 8-OHdG ameliorates liver fibrosis through the inhibition of Rac1 activation and NOX-derived ROS.


Assuntos
8-Hidroxi-2'-Desoxiguanosina/farmacologia , 8-Hidroxi-2'-Desoxiguanosina/uso terapêutico , Actinas/genética , Actinas/metabolismo , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/genética , NADPH Oxidase 1/metabolismo , NADPH Oxidase 2/genética , NADPH Oxidase 2/metabolismo , NADPH Oxidases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Proteínas rac1 de Ligação ao GTP/metabolismo , Animais , Linhagem Celular , Colágeno/genética , Colágeno/metabolismo , Modelos Animais de Doenças , Células Estreladas do Fígado , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/metabolismo , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo
11.
Pathol Int ; 70(8): 533-541, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32419286

RESUMO

Hepatocellular carcinoma (HCC) has a poor prognosis in the setting of chronic inflammation and fibrosis, both of which promote nuclear DNA oxidative damage. 8-hydroxy-deoxyguanosine (8-OHdG) DNA glycosylase (OGG1) enhances the repair of 8-OHdG, which is the primary oxidative stress-induced mutation that leads to malignant alterations. This study aims to clarify the relationships between oxidative stress-induced factors and HCC progression. The clinicopathological factors were compared with immunohistochemistry OGG1 and 8-OHdG expressions in 86 resected HCC specimens. High 8-OHdG expression was associated with high serum aspartate transaminase and total bilirubin levels, as well as a low platelet count, compared with low 8-OHdG expression. Histological liver cirrhosis and poor differentiation were more frequent in patients with high 8-OHdG expression than in those with low 8-OHdG expression. The 8-OHdG was negatively correlated with OGG1 expression in HCC patients. Therefore, we classified the patients into two groups, low OGG1/high 8-OHdG group and the other group. The patients with low OGG1/high 8-OHdG expressions had worse prognosis than those with the other expressions. Our results showed that low OGG1/high 8-OHdG expressions in nuclei influence HCC patient outcomes. Evaluating the patterns of OGG1 and 8-OHdG expressions might provide pivotal prognostic biomarkers in patients with HCC.


Assuntos
8-Hidroxi-2'-Desoxiguanosina/metabolismo , Carcinoma Hepatocelular , DNA Glicosilases/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Desoxiguanosina/metabolismo , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Cirrose Hepática/patologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Prognóstico , Espécies Reativas de Oxigênio/metabolismo , Adulto Jovem
12.
Wei Sheng Yan Jiu ; 49(3): 409-415, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32693889

RESUMO

OBJECTIVE: To determine the acute effects of exposure to fine particulate matter(PM_(2. 5))on children's respiratory inflammation and oxidative stress. METHODS: This study was a cross-sectional study. A total of 115 9-12 year-old children in boarding schools were selected as the research objects. The PM_(2. 5) exposure concentration was continuously monitored for 5 days, and the individual exposure level was estimated by using the time activity mode and the PM_(2. 5) microenvironment concentration. Exhaled breath condensate(EBC) and urine samples were collected on the 5 th day. Fractional exhaled nitric oxide(FeNO) was detected by a FeNO detector, EBC pH was measured by microelectrode potential analysis method, urine 8-hydroxydeoxyguanosine(8-OHdG) was detected by ELISA kit, and the effect of PM_(2. 5) on three effect indicators was analyzed by a linear model. RESULTS: The highest individual exposure concentration was 102 µg/m~3 4 days before the physical examination, and the lowest individual exposure concentration was 9. 19 µg/m~3 2 days before the physical examination. The FeNO of boys was higher than that of girls, and the difference was significant(P<0. 05). There were no significant differences between gender in other indicators. Correlation analysis found that there was a significant correlation between the exposure concentration of PM_(2. 5) and FeNO, and the strongest correlation was 0 to 2 days before the physical examination with each 10 µg/m~3 increase in PM_(2. 5) caused a 29. 7% increase in FeNO, other indicators did not change significantly. Gender subgroup analysis found that PM_(2. 5) had a significant effect on boys' FeNO, every 10 µg/m~3 increase in PM_(2. 5) during the study period can cause an increase in boys' FeNO of 3. 47%-50. 97%, but had no significant effect on all three indicators of girls. CONCLUSION: PM_(2. 5) had significant effects on FeNO in healthy children with immediate and delayed effects, especially on boys.


Assuntos
Poluentes Atmosféricos/análise , Testes Respiratórios , Criança , Estudos Transversais , Feminino , Humanos , Inflamação , Masculino , Óxido Nítrico/análise , Estresse Oxidativo , Material Particulado/análise
13.
Environ Health ; 18(1): 51, 2019 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-31174534

RESUMO

BACKGROUND: Growing evidence indicates that in utero arsenic exposures in humans may increase the risk of adverse health effects and development of diseases later in life. This study aimed to evaluate potential health risks of in utero arsenic exposure on genetic damage in newborns in relation to maternal arsenic exposure. METHODS: A total of 205 pregnant women residing in arsenic-contaminated areas in Hanam province, Vietnam, were recruited. Prenatal arsenic exposure was determined by arsenic concentration in mother's toenails and urine during pregnancy and in umbilical cord blood collected at delivery. Genetic damage in newborns was assessed by various biomarkers of early genetic effects including oxidative/nitrative DNA damage (8-hydroxydeoxyguanosine, 8-OHdG, and 8-nitroguanine), DNA strand breaks and micronuclei (MN) in cord blood. RESULTS: Maternal arsenic exposure, measured by arsenic levels in toenails and urine, was significantly increased (p <  0.05) in subjects residing in areas with high levels of arsenic contamination in drinking water. Cord blood arsenic level was significantly increased in accordance with maternal arsenic exposure (p <  0.001). Arsenic exposure in utero is associated with genotoxic effects in newborns indicated as increased levels of 8-OHdG, 8-nitroguanine, DNA strand breaks and MN frequency in cord blood with increasing levels of maternal arsenic exposure. Maternal toenail arsenic level was significantly associated with all biomarkers of early genetic effects, while cord blood arsenic levels associated with DNA strand breaks and MN frequency. CONCLUSIONS: In utero arsenic exposure is associated with various types of genetic damage in newborns potentially contributing to the development of diseases, including cancer, later in life.


Assuntos
Arsênio/toxicidade , Dano ao DNA/efeitos dos fármacos , Sangue Fetal/química , Exposição Materna/efeitos adversos , Micronúcleos com Defeito Cromossômico/efeitos dos fármacos , Adulto , Biomarcadores/sangue , Feminino , Humanos , Recém-Nascido , Unhas/química , Gravidez , Vietnã , Adulto Jovem
14.
Arch Toxicol ; 93(8): 2155-2164, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31363818

RESUMO

Environmental exposure to arsenic may be involved in the disturbance of DNA hypomethylation. The aim of this study is the first to explore the effect of interactions of urinary total arsenic levels, arsenic methylation capacity, 8-hydroxy-2'-deoxyguanosine (8-OHdG), plasma folate, and global 5-methyl-2'-deoxycytidine (5-MedC) levels on the risk of urothelial carcinoma (UC). A hospital-based case-control study was constructed. The research involved the histological recruitment and pathological verification of 178 UC patients and 356 age-/sex-matched controls without prior history of cancer. Arsenic species were determined by high-performance liquid chromatography (HPLC)-hydride generation and atomic absorption. 5-MedC levels were detected by HPLC and triple-quadrupole mass spectrometry (MS). 8-OHdG was processed by an online solid-phase extraction LC-MS/MS. Plasma folate levels were measured using the chemiluminescent technology. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by multiple logistic regression analysis. Results indicate that the high levels of total urinary arsenic, inorganic arsenic percentage, and 8-OHdG and the low levels of DMA % and plasma folate were independent factors of UC. In addition, global 5-MedC levels in the first quartile versus fifth quartile significantly increased the twofold OR of UC after potential factors were adjusted (95% CI:1.10-4.03). The interaction of 5-MedC level and high total arsenic level, insufficient arsenic capacity, high 8-OHdG, and low folate levels was insignificant. Results of stepwise logistic regression analysis indicate that high total urinary arsenic levels (Q3 versus Q1), low plasma folate level, and low global 5-MedC (Q4 versus Q5) significantly increased the ORs of UC. The above results suggest that high total arsenic, low plasma folate, and 5-MedC levels affect the ORs of UC independently.


Assuntos
Arsênio/urina , Metilação de DNA , Neoplasias Urológicas/metabolismo , 8-Hidroxi-2'-Desoxiguanosina/urina , Idoso , Estudos de Casos e Controles , Desoxicitidina/análogos & derivados , Desoxicitidina/sangue , Exposição Ambiental , Feminino , Ácido Fólico/sangue , Humanos , Masculino , Neoplasias Urológicas/etiologia
15.
J UOEH ; 41(4): 431-436, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31866661

RESUMO

Oxidative stress in biological components has become recognized as one of the causative factors of various diseases. In this study, we investigated the effects of worker lifestyle and fatigue on the levels of urinary 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative stress. Our results revealed that urinary 8-OHdG level was increased by alcohol intake and decreased by snack intake and adequate sleep time on the day before the survey. A decrease in urinary 8-OHdG level was also observed in parallel with a decrease in workload. Urinary 8-OHdG monitoring is expected to be useful for disease prevention in the future.


Assuntos
8-Hidroxi-2'-Desoxiguanosina/análogos & derivados , Estilo de Vida , Saúde Ocupacional , Estresse Oxidativo , 8-Hidroxi-2'-Desoxiguanosina/urina , Biomarcadores/urina , Humanos
16.
J Wound Care ; 27(11): 780-789, 2018 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-30398933

RESUMO

OBJECTIVE: This study investigated the effects of high haem oxygenase-1 (HO-1) expression on oxidative injury and the biological behaviours of rat dermal fibroblasts, under high glucose conditions. METHOD: Rat dermal fibroblasts were cultured in normal glucose (1.0g/l), high glucose (4.5g/l) or haemin (5µm). A bilirubin kit, real-time polymerase chain reaction (RT-PCR) and Western blotting measured the protease activity, mRNA, and protein levels of HO-1, respectively. An enzyme-linked immunosorbent assay (ELISA) kit measured media levels of 8-hydroxydeoxyguanosine (8-OHdG), reactive oxygen species (ROS) and collagen (hydroxyproline) secretion. Cell proliferation was measured using flow cytometry. Cell apoptosis was measured using Hoechst 33258 staining and flow cytometry. The transwell method and scratch test evaluated cell migration. RESULTS: HO-1 expression exhibited a time-dependent change that was lowest in the high glucose (HG) group at 96 hours compared with the normal glucose (NG) group. In the HG group, the 8-OHdG, ROS and cell apoptosis were increased, and collagen secretion, cell proliferation and cell migration (horizontal and vertical) were decreased compared with the NG group at 96 hours. Haemin treatment sustained high HO-1 expression for at least 96 hours, and the cells exhibited decreased 8-OHdG and ROS, increased collagen synthesis, improved proliferation and migration ability, and decreased apoptosis in the NG and haemin (NH) group/HG and haemin (HH) group compared with the NG/HG groups. These cells recovered from oxidative injury and biological behaviours dysfunction. CONCLUSION: Haemin induces HO-1 expression in fibroblasts and it may influence the oxidative injury and biological behaviours of fibroblasts. These findings suggest that HO-1 may accelerate the healing of diabetic wounds via alleviation of oxidative injury and improvement of biological behaviours of fibroblasts.


Assuntos
Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Pele/efeitos dos fármacos , Animais , Células Cultivadas/efeitos dos fármacos , Humanos , Modelos Animais , Ratos
17.
J Clin Biochem Nutr ; 62(3): 238-241, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29892162

RESUMO

Nanoparticles are widely used as useful industrial materials. Therefore, their possible adverse health effects must be appraised. We assessed and compared the oxidative DNA damage caused by four different nanoparticles (TiO2, NiO, ZnO and CeO2). The effects of the administration methods, intratracheal instillation and inhalation, were also evaluated. Rats were subjected to intratracheal instillations or 4 weeks of inhalation exposure to the nanoparticles, and the 8-hydroxydeoxyguanosine (8-OHdG) levels in the lung were analyzed by an HPLC-EC detector method. The 8-OHdG levels were increased in a dose-dependent manner with the inhalation of NiO. ZnO also increased the 8-OHdG levels with inhalation. In comparison with the control, the 8-OHdG levels were significantly and persistently higher with the CeO2 nanoparticle administration, by both intratracheal instillation and inhalation. In contrast, there were no significant differences in the 8-OHdG levels between the control and TiO2 nanoparticle-treated groups, with either intratracheal instillation or inhalation during the observation period. These results indicated that NiO, ZnO and CeO2 nanoparticles generate significant amounts of free radicals, and oxidative stress may be responsible for the lung injury caused by these nanoparticles. In addition, both intratracheal instillation and inhalation exposure induced similar tendencies of oxidative DNA damage with these nanoparticles.

18.
Indian J Clin Biochem ; 33(2): 196-201, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29651211

RESUMO

The role of bisphenol A (BPA) in autism was investigated in 49 children (mean age = 5.950 ± 1.911 years) with autism spectrum disorders (ASDs) and 40 comparable age and sex matched children used as controls (mean age = 5.333 ± 2.279 years). In addition, 8-Hydroxydeoxyguanosine (8-oxodG) was also studied as a biomarker of oxidative stress in the same set of two selected groups. The results showed that both BPA and 8-oxodG were significantly higher in children with autism than those of control children (p values = 0.025 and 0.0001, respectively). There were positive correlations between both BPA and 8-oxodG with ASDs severity (r = 0.400 and 0.805, respectively), these correlations were highly significant (p values = 0.004 and 0.001, respectively). There was a significance positive correlation between BMI and BPA, but the correlation between BMI and 8-oxodG was not significant in children with autism. The observed results revealed that BPA may increase oxidative stress resulting in mitochondrial dysfunction that affecting the behavior and functioning of ASDs children.

19.
Environ Res ; 152: 165-174, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27771571

RESUMO

BACKGROUND: We investigated whether human environmental exposure to chemicals that are labeled as (potential) carcinogens leads to increased (oxidative) damage to DNA in adolescents. MATERIAL AND METHODS: Six hundred 14-15-year-old youngsters were recruited all over Flanders (Belgium) and in two areas with important industrial activities. DNA damage was assessed by alkaline and formamidopyrimidine DNA glycosylase (Fpg) modified comet assays in peripheral blood cells and analysis of urinary 8-hydroxydeoxyguanosine (8-OHdG) levels. Personal exposure to potentially carcinogenic compounds was measured in urine, namely: chromium, cadmium, nickel, 1-hydroxypyrene as a proxy for exposure to other carcinogenic polycyclic aromatic hydrocarbons (PAHs), t,t-muconic acid as a metabolite of benzene, 2,5-dichlorophenol (2,5-DCP), organophosphate pesticide metabolites, and di(2-ethylhexyl) phthalate (DEHP) metabolites. In blood, arsenic, polychlorinated biphenyl (PCB) congeners 118 and 156, hexachlorobenzene (HCB), dichlorodiphenyltrichloroethane (DDT) and perfluorooctanoic acid (PFOA) were analyzed. Levels of methylmercury (MeHg) were measured in hair. Multiple linear regression models were used to establish exposure-response relationships. RESULTS: Biomarkers of exposure to PAHs and urinary chromium were associated with higher levels of both 8-OHdG in urine and DNA damage detected by the alkaline comet assay. Concentrations of 8-OHdG in urine increased in relation with increasing concentrations of urinary t,t-muconic acid, cadmium, nickel, 2,5-DCP, and DEHP metabolites. Increased concentrations of PFOA in blood were associated with higher levels of DNA damage measured by the alkaline comet assay, whereas DDT was associated in the same direction with the Fpg-modified comet assay. Inverse associations were observed between blood arsenic, hair MeHg, PCB 156 and HCB, and urinary 8-OHdG. The latter exposure biomarkers were also associated with higher fish intake. Urinary nickel and t,t-muconic acid were inversely associated with the alkaline comet assay. CONCLUSION: This cross-sectional study found associations between current environmental exposure to (potential) human carcinogens in 14-15-year-old Flemish adolescents and short-term (oxidative) damage to DNA. Prospective follow-up will be required to investigate whether long-term effects may occur due to complex environmental exposures.


Assuntos
Carcinógenos/metabolismo , Dano ao DNA , Exposição Ambiental , Poluentes Ambientais/metabolismo , 8-Hidroxi-2'-Desoxiguanosina , Adolescente , Bélgica , Biomarcadores/sangue , Biomarcadores/metabolismo , Biomarcadores/urina , Ensaio Cometa , Estudos Transversais , Desoxiguanosina/análogos & derivados , Desoxiguanosina/sangue , Desoxiguanosina/urina , Monitoramento Ambiental , Poluentes Ambientais/sangue , Poluentes Ambientais/urina , Feminino , Humanos , Masculino
20.
Int Arch Occup Environ Health ; 90(5): 423-431, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28181029

RESUMO

PURPOSE: Coke oven emissions containing polycyclic aromatic hydrocarbons (PAHs) are predominant toxic constituents of particulate air pollution that have been linked to increased risk of lung cancer. Numerous epidemiological studies have suggested that oxidative DNA damage may play a pivotal role in the carcinogenic mechanism of lung cancer. Little is known about the effect of interaction between PAHs exposure and lifestyle on DNA oxidative damage. METHODS: The study population is composed by coke oven workers (365) and water treatment workers (144), and their urinary levels of four PAH metabolites and 8-hydroxydeoxyguanosine (8-OHdG) were determined. Airborne samples of exposed sites (4) and control sites (3) were collected, and eight carcinogenic PAHs were detected by high-performance liquid chromatography. RESULTS: The median values of the sum of eight carcinogenic PAHs and BaP in exposed sites were significantly higher than control sites (P < 0.01). The study found that the urinary PAH metabolites were significantly elevated in coke oven workers (P < 0.01). Multivariate logistic regression analysis revealed that the risk of high levels of urinary 8-OHdG will increase with increasing age, cigarette consumption, and levels of urinary 1-hydroxypyrene, and P for trend were all <0.05. Smoking can significantly modify the effects of urinary 1-hydroxypyrene on high concentrations urinary 8-OHdG, during co-exposure to both light or heavy smoking and high 1-hydroxypyrene levels (OR 4.28, 95% CI 1.32-13.86 and OR 5.05, 95% CI 1.63-15.67, respectively). CONCLUSIONS: Our findings quantitatively demonstrate that workers exposed to coke oven fumes and smoking will cause more serious DNA oxidative damage.


Assuntos
Poluentes Ocupacionais do Ar/efeitos adversos , Exposição Ocupacional/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Hidrocarbonetos Policíclicos Aromáticos/efeitos adversos , Fumar/efeitos adversos , Adulto , Distribuição por Idade , Poluentes Ocupacionais do Ar/análise , Poluição do Ar em Ambientes Fechados/efeitos adversos , Poluição do Ar em Ambientes Fechados/análise , China , Coque , Dano ao DNA/efeitos dos fármacos , Feminino , Guanosina/análogos & derivados , Guanosina/urina , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/análise , Questionário de Saúde do Paciente , Hidrocarbonetos Policíclicos Aromáticos/urina , Fatores de Risco , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa