Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.113
Filtrar
1.
Medicine (Baltimore) ; 98(39): e17373, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574886

RESUMO

Ionizing radiation can induce deoxyribonucleic acid (DNA) methylation pattern change, and ionizing radiation-induced oxidative damage may also affect DNA methylation status. However, the influence of low-dose ionizing radiation, such as occupational radiation exposure, on DNA methylation is still controversial.By investigating the relationship between occupational radiation exposure and DNA methylation changes, we evaluated whether radiation-induced oxidative damage was related to DNA methylation alterations and then determined the relationship among occupational radiation level, DNA methylation status, and oxidative damage in interventional physicians.The study population included 117 interventional physicians and 117 controls. We measured global methylation levels of peripheral blood leukocyte DNA and expression level of DNA methyltransferase (Dnmts) and homocysteine (Hcy) in serum to assess the DNA methylation status of the body. We measured 8-hydroxy-2'-deoxyguanosine (8-OHDG) and 4-hydroxynonenal (4-HNE) levels as indices of oxidative damage. Relevance analysis between multiple indices can reflect the relationship among occupational radiation exposure, DNA methylation changes, and oxidative damage in interventional physicians.The expression levels of Dnmts, 4-HNE, and 8-OHDG in interventional physicians were higher than those in controls, while there was no statistical difference in total DNA methylation rate and expression of Hcy between interventional physicians and controls. Total cumulative personal dose equivalent in interventional physicians was positively correlated with the expression levels of Dnmts, 8-OHDG, and 4-HNE. The expression levels of 8-OHDG in interventional physicians were negatively correlated with global DNA methylation levels and positively correlated with the expression levels of Hcy.Occupational radiation exposure of interventional physicians has a certain effect on the expression of related enzymes in the process of DNA methylation, while ionizing radiation-induced oxidative damage also has a certain effect on DNA methylation. However, there was no evidence that dose burden of occupational exposure was associated to changes of DNA methylation status of interventional physicians, since it is rather unclear which differences are observed among the effects produced by radiation exposure and oxidative damage.


Assuntos
Dano ao DNA/efeitos da radiação , Metilação de DNA/efeitos da radiação , Exposição Ocupacional/análise , Estresse Oxidativo/efeitos da radiação , Exposição à Radiação/análise , Radiologia Intervencionista/estatística & dados numéricos , Adulto , Aldeídos/sangue , Desoxiguanosina/análogos & derivados , Desoxiguanosina/sangue , Feminino , Homocisteína/sangue , Humanos , Leucócitos/metabolismo , Masculino , Metiltransferases/sangue , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Médicos/estatística & dados numéricos , Exposição à Radiação/efeitos adversos
2.
Medicine (Baltimore) ; 98(32): e16518, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393354

RESUMO

BACKGROUND: The main objective was to evaluate and compare the local genotoxicity of sevoflurane and desflurane in bronchoalveolar cells, while the secondary outcome was to detect systemic oxidative DNA damage. To our knowledge, our study is the first one to evaluate the local effects of inhalation anesthetics in human bronchoalveolar cells in patients. METHODS: American Society of Anesthesiologists group I-II patients scheduled for lumbar discectomy surgery were enrolled in this randomized prospective study. Patients were randomized to sevoflurane or desflurane for anesthesia maintenance. Bronchoalveolar lavage samples and peripheral blood samples were taken at 2-time points: the first point (baseline, T1); and the second point (postexposure, T2). Final number of 48 samples were the sevoflurane (n = 22) and desflurane (n = 26) groups. Comet assay was applied to examine genotoxic properties. Oxidative DNA damage in plasma was measured with 8-hydroxy-2'-deoxyguanosine (8-OHdG). RESULTS: T2 values were higher than baseline values in both the desflurane group (tail-length: 66 ±â€Š24, %DNA in tail: 72 ±â€Š60, tail moment: 47.52 ±â€Š14.4; P = .001, P = .005, P = .001, respectively) and the sevoflurane group (tail-length: 58 ±â€Š33, %DNA in tail: 88 ±â€Š80, tail moment: 51.04 ±â€Š26.4; P = .001, P = .012, P = .001, respectively). T2 plasma 8-OHdG levels were also higher than baseline levels in the desflurane group (3.91 ±â€Š0.19 ng/ml vs 1.32 ±â€Š0.20 ng/ml, P = .001) and sevoflurane group (3.98 ±â€Š0.18 ng/ml vs 1.31 ±â€Š0.11 ng/ml, P = .001). There were no differences between the 2 groups in comet parameters and 8-OHdG levels. CONCLUSION: Our results indicate that both inhalation agents cause DNA damage in the bronchoalveolar cells. Also, we detected increases in plasma 8-OHdG concentrations. Local genotoxicity and systemic oxidized DNA damage were similar in both groups.


Assuntos
Anestésicos Inalatórios/efeitos adversos , Anestésicos Inalatórios/farmacologia , Líquido da Lavagem Broncoalveolar/citologia , Dano ao DNA/efeitos dos fármacos , Adulto , Idoso , Ensaio Cometa , Desoxiguanosina/análogos & derivados , Desoxiguanosina/sangue , Desflurano/efeitos adversos , Desflurano/farmacologia , Discotomia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Estudos Prospectivos , Sevoflurano/administração & dosagem , Sevoflurano/farmacologia
3.
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
4.
Chem Pharm Bull (Tokyo) ; 67(7): 707-712, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31257326

RESUMO

Hypobromous acid (HOBr) is generated not only by eosinophils but also by neutrophils in the presence of Br- at the plasma concentration. Reactivity of HOBr is greatly modulated by coexistent compounds such as amines and amides. In this study, we investigated effects of urea in the reaction of nucleosides with HOBr. When nucleosides were incubated with HOBr without urea in potassium phosphate buffer at pH 7.4 and 37°C, the reactions almost completed within 10 min, with consumptions in the order of 2'-deoxyguanosine > 2'-deoxycytidine > 2'-deoxythymidine > 2'-deoxyadenosine, generating 8-bromo-2'-deoxyguanosine and 5-bromo-2'-deoxycytidine. In the presence of urea, the reaction of nucleosides with HOBr was relatively slow, continuing over several hours. When HOBr was preincubated without urea in potassium phosphate buffer at pH 7.4 and 37°C for 48 h, the preincubated HOBr solution did not react with nucleosides. However, a similar preincubated solution of HOBr with urea reacted with nucleosides to generate 8-bromo-2'-deoxyguanosine and 5-bromo-2'-deoxycytidine. These results imply that a reactive bromine compound with a long life, probably bromourea, is generated by HOBr in neutral urea solution and reacts with nucleosides, resulting in brominated nucleosides.


Assuntos
Bromatos/química , Nucleosídeos/química , Ureia/química , Cromatografia Líquida de Alta Pressão , Desoxicitidina/química , Desoxiguanosina/análogos & derivados , Desoxiguanosina/análise , Desoxiguanosina/química , Halogenação , Fosfatos/química , Compostos de Potássio/química , Espectrometria de Massas por Ionização por Electrospray , Timidina/química
5.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(3): 193-198, 2019 May.
Artigo em Chinês | MEDLINE | ID: mdl-31257797

RESUMO

OBJECTIVE: To investigate the vascular damage effects and possible mechanism of acute exposure to ozone (O3) in male Wistar rats. METHODS: One hundred and twenty male Wistar rats were randomly divided into six groups, 20 in each group. The experimental animals were placed in a gas poisoning cabinet, the control group was exposed to filtered air, and the treatment group was exposed to ozone at concentrations of 0.12 ppm, 0.5 ppm, 1.0 ppm, 2.0 ppm, and 4.0 ppm, respectively, for 4 hours. Arterial blood pressure data were obtained by PC-lab medical physiological signal acquisition system. Blood rheology indicators and blood biochemical indicators were detected by Tianjin Dean Diagnostic Laboratory. Serum endothelin-1 (ET-1), homocysteine (HCY), von Willebrand factor (vWF), 8-hydroxydeoxyguanosine (8-OhdG), interleukin (IL-6) and tumor necrosis factor alpha (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA) microplate assay. Oxidative stress indicators superoxide dismutase (SOD) activity and malondialdehyde (MDA) were determined by xanthine oxidase method, thiobarbituric acid (TBA) method, reduced glutathione (GSH) and nitric oxide (NO) were tested by using microplate colorimetry. Paraffin sections were prepared from thoracic aorta tissue, and vascular structure was observed by HE staining. RESULTS: Acute exposure to 0.12 ppm ozone could cause a significant increase in arterial systolic blood pressure (SBP). Exposure to different concentrations of ozone could cause a significant increase in plasma viscosity, and the K value of the ESR equation was significantly increased in the 1.0 ppm ozone exposure group. Both the relative and reduced viscosities were significantly reduced at ozone concentrations of 0.5 ppm and 4.0 ppm, while the red blood cell deformation index was increased significantly at ozone concentrations of 0.12 ppm, 0.5 ppm, 1.0 ppm, and 2.0 ppm. Acute ozone exposure resulted in the decrease of total cholesterol content. The content of high-density lipoprotein cholesterol (HDL-C) was significantly reduced in the 0.12 ppm ozone exposure group. When the ozone concentration was higher than 1.0 ppm, the body may also had an inflammatory reaction (increased TNF-α) and oxidative stress (increased MDA, decreased GSH). Acute exposure to ozone could lead to elevated levels of ET-1 in the blood, with significant differences in the 4.0 ppm concentration group, while HCY levels were decreased firstly and then increased, reaching the highest in the 1.0 ppm concentration group. No obvious pathological changes were observed in the thoracic aorta. CONCLUSION: Acute ozone exposure can affect arterial blood pressure, blood rheology and cholesterol metabolism in rats. The possible mechanism is that ozone exposure leads to inflammatory reaction and oxidative stress reaction, causing vascular endothelial function damage, and vascular endothelial cells increase with ozone exposure concentration.


Assuntos
Vasos Sanguíneos/lesões , Estresse Oxidativo , Ozônio/toxicidade , Animais , Desoxiguanosina/análogos & derivados , Desoxiguanosina/sangue , Endotelina-1/sangue , Homocisteína/sangue , Interleucina-6/sangue , Masculino , Malondialdeído/análise , Ratos , Ratos Wistar , Superóxido Dismutase/análise , Fator de Necrose Tumoral alfa/sangue , Fator de von Willebrand/análise
6.
J Physiol Pharmacol ; 70(1)2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31172968

RESUMO

The etiopathogenesis of potentially malignant oral disorders (PMOD) has not been fully understood yet. Recent results suggest that oxidative stress may be involved in the etiology of PMOD. Production of oxidants seems to be the major biological effect responsible for tissue injury and inflammatory response to air pollution. The aim of this study was to compare the oxidative stress markers and antioxidant potential in saliva of PMOD subjects and healthy controls in periods of high and low air pollution. Among enrolled 40 participants, there were 20 PMOD patients and 20 healthy volunteers. The exposure to air pollution was assessed by exhaled CO (eCO). Four oxidative status parameters: 8-hydroxy-2'-deoxyguanosine (8-OHdG), malondialdehyde (MDA), reduced glutathione (GSH) and total antioxidant capacity (TAC) were measured in saliva. Measurements were carried out in June (low air pollution) and November (increased air pollution). In both groups, significantly higher concentrations of 8-OHdG (P < 0.001 for PMOD patients and P = 0.001 for healthy controls), MDA (P = 0.002 and P = 0.012 respectively) and eCO (P < 0.001 and P < 0.001 respectively) were observed in periods of high air pollution. The concentration of TAC did not change between visits. The concentration of salivary GSH (P < 0.001 and P < 0.001 for both groups) decreased when compared between consecutive visits. We conclude that exhaled carbon monoxide (reflecting exposure to air pollution) correlated with the oxidative stress markers in patients with PMOD and healthy controls.


Assuntos
Poluição do Ar , Monóxido de Carbono/metabolismo , Exposição Ambiental , Doenças da Boca/metabolismo , Estresse Oxidativo , Saliva/metabolismo , Idoso , Biomarcadores/metabolismo , Testes Respiratórios , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Expiração , Feminino , Glutationa/metabolismo , Humanos , Masculino , Malondialdeído/metabolismo , Pessoa de Meia-Idade , Polônia
7.
Anticancer Res ; 39(6): 3241-3248, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31177174

RESUMO

BACKGROUND/AIM: The effects of oxidative stress on various carcinomas were reported in previous studies, but those in intrahepatic cholangiocarcinoma (ICC) have not been fully elucidated. The purpose of this study was, thus, to reveal the effects of oxidative DNA damage and repair enzymes on ICC. MATERIALS AND METHODS: The levels of 8-hydroxydeoxyguanosine (8-OHdG) and 8-OHdG DNA glycosylase (OGG1) were immunohistochemically evaluated in specimens resected from 63 patients with ICC. RESULTS: Low OGG1 expression was related to tumour depth T4 (p=0.04), venous invasion (p=0.0005), lymphatic vessel invasion (p=0.03), and perineural invasion (p=0.03). Compared to the high-OGG1-expression group, patients with low OGG1 expression had a significantly poorer prognosis (overall survival: p=0.04, recurrence-free survival: p=0.02). Unlike for OGG1, the expression levels of 8-OHdG showed no association with prognosis. CONCLUSION: Oxidative DNA damage and DNA repair enzymes may be closely related to ICC progression.


Assuntos
Neoplasias dos Ductos Biliares/enzimologia , Biomarcadores Tumorais/análise , Colangiocarcinoma/enzimologia , DNA Glicosilases/análise , Reparo do DNA , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/terapia , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Colangiocarcinoma/terapia , Dano ao DNA , Desoxiguanosina/análogos & derivados , Desoxiguanosina/análise , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Intervalo Livre de Progressão , Estudos Retrospectivos , Fatores de Tempo
8.
Environ Sci Pollut Res Int ; 26(22): 22562-22574, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31165450

RESUMO

Zingerone (ZO), one of the active components of ginger (Zingiber officinale), is a phenolic alkanone with antioxidant, antiapoptotic, and anti-inflammatory properties. Cisplatin (CP) is a widely used chemotherapeutic drug for solid tumors, but its therapeutic use is limited due to dose-dependent nephrotoxicity. In the present study, we investigated the ameliorative effect of ZO against CP-induced nephrotoxicity. Intraperitoneal administration of single-dose CP (7 mg/kg body weight) on the first day enhanced kidney lipid peroxidation and reduced antioxidant enzyme activities such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione (GSH). CP increased serum urea and creatinine levels and disrupted histological integrity while causing a decrease aquaporin 1 (AQP1) level in the kidney tissues. CP induced inflammatory responses by elevating the levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-33 (IL-33) and nuclear factor kappa B (NF-κB), and activities of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, it also caused oxidative DNA damage and activation of apoptotic pathway by increasing of 8-hydroxy-2'-deoxyguanosine (8-OHdG), p53, cysteine aspartate-specific protease-3 (caspase-3), and Bcl-2-associated x protein (bax) while decreasing B cell lymphoma-2 (Bcl-2). However, treatment with ZO at a dose of 25 and 50 mg/kg b.wt. for 7 days significantly decreased oxidative stress, apoptosis, inflammation, and histopathological alterations while increased AQP1 levels in the kidney tissue. The results of the current study suggested that ZO as an effective natural product attenuates CP-induced nephrotoxicity.


Assuntos
Antioxidantes/metabolismo , Cisplatino/toxicidade , Guaiacol/análogos & derivados , Rim/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Autofagia , Nitrogênio da Ureia Sanguínea , Catalase/metabolismo , Dano ao DNA , Desoxiguanosina/análogos & derivados , Feminino , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Guaiacol/metabolismo , Inflamação/metabolismo , Interleucina-6/metabolismo , Rim/metabolismo , Peroxidação de Lipídeos , Masculino , NF-kappa B/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Ratos , Superóxido Dismutase/metabolismo , Testes de Toxicidade , Fator de Necrose Tumoral alfa/metabolismo
9.
Cell Mol Biol (Noisy-le-grand) ; 65(4): 53-62, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31078153

RESUMO

Thyroid hormones regulate the development and maturation of the brain by maintaining levels of neurotransmitters and their related metabolites. The present work emphasizes the neural dysfunction in the brain caused by hypothyroidism and the potential role of Hordeum vulgare (water soluble barley, (B)) in ameliorating these effects. The study was conducted on euothyroid and hypothyroid adult female rats. The induction of hypothyroidism was conducted by oral-administration of neo-mercazole (5.0 mg.kg-1) daily for thirty days prior the study and terminated at the end of the study. The groups were assigned as; euthyroid (EU) and hypothyroid (H) groups and other two groups were treated with 100 mg.kg-1 water soluble barley; daily for one month and assigned as (EU+B) and (H+B) groups. Compared with EU and EU+B groups, a reduction in fT4, and ERK1/2 levels and elevation in TSH in brain tissue, Moreover, a  significant elevation in 8-OH deoxyguanosine and caspase-3 levels, confirmed with increase percentage DNA-damage in the brain and thyroid tissues in hypothyroid control rats. Furthermore, a significant decrease in all monoamines levels in different brain areas and downregulation of dopamine and 5-hydroxytreptamin receptors transcription, with a significant increase in excitatory amino acids and no significant change in the levels inhibitory amino acids were recorded in control hypothyroid group. Treatment of hypothyroid group with Hordeum vulgare improved the above-mentioned adverse impact by ameliorating the thyroid hormone levels with depleting the DNA-degradation and elaborating the levels of neurotransmitters with related receptors and amino acids in brain areas.  Water soluble Hordeum vulgare as a phytonutrient, is safe and efficient agent in ameliorating the neural dysfunction resulting from hypothyroidism status in adult female rats.


Assuntos
Monoaminas Biogênicas/metabolismo , Hordeum/química , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/fisiopatologia , Sistema Nervoso/fisiopatologia , Extratos Vegetais/uso terapêutico , Glândula Tireoide/fisiopatologia , Aminoácidos/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Caspase 3/metabolismo , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Sistema Nervoso/efeitos dos fármacos , Neurotransmissores/metabolismo , Extratos Vegetais/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar , Glândula Tireoide/efeitos dos fármacos , Hormônios Tireóideos/genética , Hormônios Tireóideos/metabolismo
10.
Chemistry ; 25(44): 10408-10419, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31062885

RESUMO

Nucleoside configuration (α-d vs. ß-d), nucleobase substituents, and the helical DNA environment of silver-mediated 5-aza-7-deazaguanine-cytosine base pairs have a strong impact on DNA stability. This has been demonstrated by investigations on oligonucleotide duplexes with silver-mediated base pairs of α-d and ß-d anomeric 5-aza-7-deaza-2'-deoxyguanosines and anomeric 2'-deoxycytidines incorporated in 12-mer duplexes. To this end, a new synthetic protocol has been developed to access the pure anomers of 5-aza-7-deaza-2'-deoxyguanosine by glycosylation of either the protected nucleobase or its salt followed by separation of the glycosylation products by crystallization and chromatography. Thermal stability measurements were performed on duplexes with α-d/α-d and ß-d/ß-d homo base pairs or α-d/ß-d and ß-d/α-d hybrid pairs within two sequence environments, positions 6 or 7, of oligonucleotide duplexes. The respective Tm stability increases observed after silver ion addition differ significantly. Homo base pairs with ß-d/ß-d or α-d/α-d nucleoside combinations are more stable than α-d/ß-d hybrid base pairs. The positional switch of silver-ion-mediated base pairs has a significant impact on stability. Nucleobase substituents introduced at the 5-position of the dC site of silver-mediated base pairs affect base pair stability to a minor extent. Our investigation might lead to applications in the construction of bioinspired nanodevices, in DNA diagnostics, or metal-DNA hybrid materials.


Assuntos
DNA/química , Desoxiguanosina/análogos & derivados , Prata/química , Pareamento Incorreto de Bases , Pareamento de Bases , Cátions Monovalentes , Citosina/química , Desoxicitidina/química , Desoxiguanosina/química , Glicosilação , Guanina/análogos & derivados , Guanina/química , Modelos Moleculares , Conformação de Ácido Nucleico , Oligonucleotídeos/síntese química , Oligonucleotídeos/química , Relação Estrutura-Atividade , Termodinâmica
11.
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
12.
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
13.
Transplant Proc ; 51(4): 1049-1053, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31101169

RESUMO

BACKGROUND: Long-term consequences of donor nephrectomy might be reduced kidney function, increased risk for cardiovascular disease, and impaired quality of life. The purpose of the current cross-sectional study was to evaluate the relationship between clinical, laboratory, and donation-specific outcomes of living kidney donors and systemic oxidative DNA damage. METHODS: We conducted a cross-sectional study and assessed retrospectively pre- and postdonation data from 60 donors who donated between 2010 and 2015. Plasma malondialdehyde levels and 8-hydroxy-2'-deoxyguanosine/deoxyguanosine ratio (8-OHdG/dG ratio) were determined as oxidative stress markers. Catalase, carbonic anhydrase, and paraoxonase (PON) activities were measured as antioxidants. RESULTS: Approximately 3 years after donation, the hypertensive donor ratio was 12%, and 11% of the donors had glomerular filtration rate <60 mL/min/1.73 m2. Mean serum urea (P = .001) and serum creatinine levels (P = .001) were increased; creatinine clearance level (126.2 ± 35.5 vs 94.6 ± 26.8, P = .001) was decreased in the postdonation period. There was a significant positive correlation between predonation serum urea and 8-0HdG/dG ratio (r = 0.338, P = .016) and predonation serum creatinine and 8-0HdG/dG ratio (r = 0.442, P = .001), while there was a significant negative correlation between serum creatinine and PON activity (r = -0.545, P < .001). CONCLUSION: Our data have demonstrated that kidney donors exhibit increased oxidative DNA damage and decreased antioxidant activity. We propose that predonation serum creatinine is positively correlated with 8-0HdG/dG ratio and negatively correlated with antioxidant PON activity. This is the first study to demonstrate that plasma oxidative DNA damage increases in healthy kidney donors.


Assuntos
Antioxidantes , Dano ao DNA , Nefrectomia/efeitos adversos , Estresse Oxidativo , Adulto , Biomarcadores/sangue , Creatinina/sangue , Estudos Transversais , Desoxiguanosina/análogos & derivados , Desoxiguanosina/sangue , Feminino , Humanos , Doadores Vivos , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Estudos Retrospectivos , Coleta de Tecidos e Órgãos/efeitos adversos
14.
Chem Commun (Camb) ; 55(48): 6850-6853, 2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31123731

RESUMO

PAGE and UV melting analysis revealed that longer LNA-based splice-switching oligonucleotides (SSOs) formed secondary structures by themselves, reducing their effective concentration. To avoid such secondary structure formation, we introduced 7-deaza-2'-deoxyguanosine or 2'-deoxyinosine into the SSOs. These modified SSOs, with fewer secondary structures, showed higher exon skipping activities.


Assuntos
Éxons , Oligonucleotídeos/química , Desoxiguanosina/análogos & derivados , Desoxiguanosina/química , Inosina/análogos & derivados , Inosina/química , Conformação de Ácido Nucleico , Oxirredução
15.
Methods Mol Biol ; 1973: 15-25, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31016693

RESUMO

Formation of adducts to DNA is of great benefit to DNA sequencing and damage detection technology and to enzymology. Here we describe the synthesis and characterization procedures of 18-crown-6 adducts formed to abasic (AP) sites, 8-oxo-7,8-dihydro-2'-deoxyguanosine (OG), and 2'-deoxycytidine (C) residues in DNA oligodeoxynucleotides. These crown ether adducts were used as site-specific modifications to facilitate nanopore technology. The methods described can be readily expanded to attach other suitable primary amines of interest.


Assuntos
Éteres de Coroa/química , Adutos de DNA/química , DNA/biossíntese , Desoxicitidina/química , Desoxiguanosina/análogos & derivados , Oligodesoxirribonucleotídeos/química , DNA/química , Desoxiguanosina/química , Nanoporos
16.
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
17.
Int J Pediatr Otorhinolaryngol ; 122: 70-75, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30978472

RESUMO

OBJECTIVES: Cisplatin is employed for chemotherapeutic purposes in several types of adult and pediatric cancer. However, side-effects including nephrotoxicity, ototoxicity, gastrointestinal effects and neuropathy restrict the use of the drug due to their adverse impacts on quality of life. This study aimed to determine whether levosimendan exhibits a protective effect against cisplatin-related ototoxicity in a rat model by means of functional, biochemical and histochemical analysis. METHODS: The study was employed with 24 female Sprague Dawley rats. After distortion product otoacoustic emissions (DPOAE) tests applied to all rats, rats were randomly assigned into four groups of six animals each. A single intraperitoneal 15 mg/kg dose of cisplatin was administered to Cisplatin group. Levosimendan group received intraperitoneal levosimendan at a dose of 100 mg/kg for five consecutive days. Cisplatin + Levosimendan group received intraperitoneal levosimendan at a dose of 100 mg/kg for five consecutive days and a single intraperitoneal dose of 15 mg/kg cisplatin at 3rd day of the study. Control group received 8 mL/kg/day intraperitoneal saline solution for five consecutive days. The DPOAE test was repeated on the 6th day of the study. All rats were then sacrificed, the cochleas were removed and set aside for biochemical and histopathological analyses. RESULTS: A significant increase in levels of Malondialdehyde (MDA) and significantly lower activities of superoxide dismutase (SOD) and Glutathione peroxidase (GPx) were observed at rats of cisplatin group. Administration of levosimendan showed significantly lower cochlear MDA levels, while SOD and GPx activities both increased significantly. The DPOAE test performed at 6th day of the study showed a significant impairment in the signal-noise ratio (SNR) levels of rats in Cisplatin group. The SNR levels of rats treated with levosimendan were significantly higher than those of cisplatin group and were similar to those of the control group. Cisplatin impaired the cochlear structure and a severe Caspase 3 and 8-hydroxy-2' -deoxyguanosine (8-OHdG) immunopositivity was observed at cochlea of the rats of cisplatin group. Administration of levosimendan protected the structure of cochlea and there was a mild Caspase 3 and 8OHdG immunopositivity. CONCLUSION: Our data demonstrate that levosimendan protects hearing against cisplatin-induced ototoxicity and obviates cellular degeneration. It also significantly reduces oxidative stress and apoptosis, probable mechanisms involved in ototoxicity.


Assuntos
Cóclea/metabolismo , Cóclea/patologia , Perda Auditiva/prevenção & controle , Inibidores da Fosfodiesterase 3/uso terapêutico , Simendana/uso terapêutico , Animais , Antineoplásicos/efeitos adversos , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Cisplatino/efeitos adversos , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Modelos Animais de Doenças , Feminino , Glutationa Peroxidase/metabolismo , Audição/efeitos dos fármacos , Perda Auditiva/induzido quimicamente , Perda Auditiva/fisiopatologia , Malondialdeído/metabolismo , Emissões Otoacústicas Espontâneas/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Razão Sinal-Ruído , Superóxido Dismutase/metabolismo
18.
Talanta ; 199: 324-328, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30952266

RESUMO

In this work, an electrochemical method for sensitive analysis of 8-hydroxy-2'-deoxyguanosine, a key biomarker that is widely used to study oxidative injury-related diseases, is proposed based on exonuclease-mediated functional nucleic acid. In the design, exonuclease can not only distinguish the existence of target, but also suppress the background noise, thus the sensitivity can be enhanced. Moreover, DNAzyme designed in the functional nucleic acid can further improve the sensitivity of the analysis during signal generation process. Therefore, exonuclease-mediated functional nucleic acid may ensure high sensitivity of the assay. Further studies reveal that the detection of 8-hydroxy-2'-deoxyguanosine can be achieved with a linearity from 0.01 nM to 7.0 µM and a detection limit of 6.82 pM. The new method has also been successfully applied to the determination of 8-OHdG in urine with good results, indicating its great potential for practical use.


Assuntos
Técnicas Biossensoriais , DNA/química , DNA/metabolismo , Desoxiguanosina/análogos & derivados , Técnicas Eletroquímicas , Exonucleases/metabolismo , Desoxiguanosina/análise , Eletrodos , Ouro/química , Humanos
19.
Oncol Rep ; 41(5): 3041-3050, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30964148

RESUMO

Reactive oxygen species (ROS) accumulation is known to induce carcinogenesis and accelerate cancer progression. 8­Hydroxydeoxyguanosine (8­OHdG) is a specific marker of ROS­mediated DNA damage. Therefore, we analysed 8­OHdG levels in cancerous and normal tissue DNA via enzyme­linked immunosorbent assay (ELISA) using 97 tissue specimens obtained from surgically­treated patients with stage II/III colorectal cancer (CRC). Additionally, 8­OHdG levels in these tissues were also assessed via quantitative immunohistochemistry (qIHC). To eliminate individual background variables, the ratio of 8­OHdG levels between cancerous and normal tissues was calculated using both techniques. A comparative analysis demonstrated that the 8­OHdG ratio in DNA was significantly correlated with both lymph node metastasis and lymphatic invasion. Multivariate analysis revealed that a high 8­OHdG ratio in DNA was independently correlated with poor prognosis. These results suggest that the 8­OHdG ratio in DNA reflects ROS­induced cancer progression. Conversely, a low 8­OHdG ratio as estimated via qIHC was an independent factor for poor prognosis. In Kaplan­Meier analysis, the combination of a high 8­OHdG ratio in DNA (ELISA) and a low 8­OHdG ratio in cytoplasm (qIHC) was associated with markedly worse patient prognosis than other combinations. Combined evaluation of the 8­OHdG ratio using ELISA and qIHC may be pivotal for predicting surgical outcomes for patients with stage II/III CRC.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias Colorretais/diagnóstico , DNA de Neoplasias/química , Desoxiguanosina/análogos & derivados , Idoso , Biomarcadores Tumorais/química , Colo/patologia , Colo/cirurgia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Citoplasma/química , Desoxiguanosina/análise , Desoxiguanosina/química , Intervalo Livre de Doença , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática/diagnóstico , Metástase Linfática/patologia , Masculino , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico
20.
Environ Sci Pollut Res Int ; 26(13): 12709-12719, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30879234

RESUMO

Co-exposure to carboxylic acid functionalized multi-walled carbon nanotubes (F-MWCNTs) and polycyclic aromatic hydrocarbons (PAHs) such as benzo a pyrene (BaP) in ambient air have been reported. Adsorption of BaP to F-MWCNTs can influence combined toxicity. Studying individual toxicity of F-MWCNTs and BaP might give unrealistic data. Limited information is available on the combined toxicity of F-MWCNTs and BaP in human cells. The objective of the present work is to evaluate the toxicity of F-MWCNTs and BaP individually and combined in human lung adenocarcinoma (A549 cells). The in vitro toxicity is evaluated through cell viability, the production of reactive oxygen species (ROS), apoptosis, and the production of 8-OHdG assays. Adsorption of BaP to F-MWCNTs was confirmed using a spectrophotometer. The results indicated that the F-MWCNTs and BaP reduce cell viability individually and produce ROS, apoptosis, and 8-OHdG in exposed cells. Stress oxidative is found to be a mechanism of cytotoxicity for both F-MWCNTs and BaP. Combined exposure to F-MWCNTs and BaP decreases cytotoxicity compared to individual exposure, but the difference is not statistically significant in all toxicity assays; hence, the two-factorial analysis indicated an additive toxic interaction. Adsorption of BaP to F-MWCNTs could mitigate the bioavailability and toxicity of BaP in biological systems. Considering the mixture toxicity of MWCNTs and BaP is required for risk assessment of ambient air contaminants.


Assuntos
Benzo(a)pireno/toxicidade , Ácidos Carboxílicos/toxicidade , Nanotubos de Carbono/toxicidade , Células A549 , Apoptose/efeitos dos fármacos , Ácidos Carboxílicos/química , Sobrevivência Celular/efeitos dos fármacos , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Humanos , Hidrocarbonetos Policíclicos Aromáticos , Espécies Reativas de Oxigênio/metabolismo , Testes de Toxicidade/métodos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA