8-hydroxy-2--deoxyguanosine and Chronic-Disease

Currently, there are no satisfactory biomarkers available to screen for nasopharyngeal carcinoma (NPC). Nitric oxide (NO), produced by inducible nitric oxide synthase (iNOS), has been suggested to cause nitrative and oxidative stress, leading to the accumulation of 8-nitroguanine (8-NitroG) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) and the subsequent transversion mutation of DNA. The aim of this study was to evaluate iNOS expression and the status of nitrative and oxidative stress in NPC. Fifty-nine cases of NPC and 39 cases of chronic nasopharyngitis were investigated to examine the expression of iNOS and the formation of 8-NitroG and 8-OHdG, using double-immunofluorescent staining. The statistical differences in immunoreactivities were analyzed using the Mann-Whitney test. Thirty-six patients from the 57 cases of NPC and 36 healthy controls were investigated to examine the level of serum 8-OHdG, using enzyme-linked immunosorbent assay (ELISA). The statistical differences were analyzed using a t test. Strong DNA lesions were observed in the cancer cells of NPC patients. All cases of NPC were positive for 8-NitroG and 8-OHdG, and 54 (94.7%) were positive for iNOS. NPC samples exhibited significantly more intense staining for 8-NitroG, 8-OHdG and iNOS than those of chronic nasopharyngitis (P < 0.05, respectively). The mean value of serum 8-OHdG in the 36 NPC patients was 0.538 ± 0.336 ng/ml compared to 0.069 ± 0.059 ng/ml for the healthy controls. The difference in the serum levels of 8-OHdG between the NPC patients and controls was statistically significant (P < 0.05). Our present findings suggest that pathological stimulation of nasopharyngeal tissue, caused by bacterial, viral or parasitic inflammation, may lead to nitrative and oxidative DNA lesions, caused by NO. This may contribute to the cause and development of NPC. Thus, 8-NitroG and 8-OHdG could be potential biomarkers for evaluating the risk of NPC. Better understanding of the molecular mechanisms underlying nitrative and oxidative DNA damage may provide clues to molecular targets for new approaches of NPC prevention.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Chronic Disease; Deoxyguanosine; DNA Damage; DNA, Neoplasm; Enzyme-Linked Immunosorbent Assay; Female; Guanine; Humans; Immunoenzyme Techniques; Male; Middle Aged; Nasopharyngeal Neoplasms; Nasopharyngitis; Nasopharynx; Nitric Oxide Synthase Type II; Oxidation-Reduction; Oxidative Stress; Prognosis

Chile is a mining country, where waste mining is frequently found in the vicinity of inhabited areas. To explore the association between metal exposure and alterations in glucose metabolism, inflammatory status, and oxidative stress in individuals with chronic exposure to metals, a cross-sectional study was performed with 25 volunteers, between 45-65 years old. Inductive coupled plasma mass spectrometry (ICP-MS) was used to measure urinary levels of total arsenic (As) and its metabolites, cooper, nickel, chromium, and lead. Lipid profile, glucose, and insulin were measured in blood, as well as inflammation (interleukin-6, IL-6) and oxidative stress (8-hydroxy-2'deoxyguanosine, 8-OHdG) markers. Increased levels of Low-density lipoprotein, high-density lipoproteins, cholesterol and 8-OHdG, and the index for homeostasis model assessment-insulin resistance (HOMA-IR) were observed in 72%, 60%, and 56% of the volunteers, respectively. Blood-glucose levels were correlated with dimethylarsinic acid (DMA) (R

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Chile; Chronic Disease; Cross-Sectional Studies; Humans; Insulin Resistance; Metals, Heavy; Middle Aged

Cardiovascular complications are the leading cause of morbidity and mortality at any stage of chronic kidney disease (CKD). Moreover, the high rate of cardiovascular mortality observed in these patients is associated with an accelerated atherosclerosis process that likely starts at the early stages of CKD. Thus, traditional and non-traditional or uremic-related factors represent a link between CKD and cardiovascular risk. Among non-conventional risk factors, particular focus has been placed on anaemia, mineral and bone disorders, inflammation, malnutrition and oxidative stress and, in this regard, connections have been reported between oxidative stress and cardiovascular disease in dialysis patients.. We evaluated the oxidation process in different molecular lines (proteins, lipids and genetic material) in 155 non-dialysis patients at different stages of CKD and 45 healthy controls. To assess oxidative stress status, we analyzed oxidized glutathione (GSSG), reduced glutathione (GSH) and the oxidized/reduced glutathione ratio (GSSG/GSH) and other oxidation indicators, including malondialdehyde (MDA) and 8-oxo-2'-deoxyguanosine (8-oxo-dG).. An active grade of oxidative stress was found from the early stages of CKD onwards, which affected all of the molecular lines studied. We observed a heightened oxidative state (indicated by a higher level of oxidized molecules together with decreased levels of antioxidant molecules) as kidney function declined. Furthermore, oxidative stress-related alterations were significantly greater in CKD patients than in the control group.. CKD patients exhibit significantly higher oxidative stress than healthy individuals, and these alterations intensify as eGFR declines, showing significant differences between CKD stages. Thus, future research is warranted to provide clearer results in this area.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Chronic Disease; Humans; Malondialdehyde; Oxidation-Reduction; Oxidative Stress; Renal Insufficiency, Chronic

Systemic oxidative stress plays a key role in the development of chronic heart failure (CHF). We tested the hypothesis that mitochondrial reactive oxygen species (ROS) generation in circulating peripheral blood mononuclear cells (PBMCs) contributes to CHF progression. A total of 31 patients who had a history of hospital admission due to worsening HF were enrolled and grouped as having either mild CHF defined as New York Heart Association (NYHA) functional class I-II or moderate-to-severe CHF defined as NYHA functional class III. ROS levels in PBMC mitochondria were significantly increased in CHF patients with NYHA functional class III compared to those with NYHA functional class I-II, accompanied by impaired mitochondrial respiratory capacity in PBMCs. ROS generation in PBMC mitochondria was positively correlated with urinary 8-hydroxydeoxyguanosine, a systemic oxidative stress marker, in CHF patients. Importantly, mitochondrial ROS generation in PBMCs was directly correlated with plasma levels of B-type natriuretic peptide, a biomarker for severity of HF, and inversely correlated with peak oxygen uptake, a parameter of exercise capacity, in CHF patients. The study showed that ROS generation in PBMC mitochondria was higher in patients with advanced CHF, and it was associated with disease severity and exercise intolerance in CHF patients.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Biomarkers; Chronic Disease; Exercise Test; Exercise Tolerance; Female; Heart Failure; Humans; Leukocytes, Mononuclear; Male; Middle Aged; Mitochondria; Natriuretic Peptide, Brain; Oxygen Consumption; Reactive Oxygen Species; Severity of Illness Index

Warts are benign conditions of the skin and mucosa caused by human papilloma viruses (HPV) that affect many people worldwide.. The aim of this study was to evaluate OS by TOS/TAS, levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) an indicator of DNA damage, and also protein oxidation levels by determining the dynamic serum thiol/disulphide homeostasis in patients with warts. We also aimed to investigate whether there is a relationship between thiol/disulphide homeostasis, recalcitrance of warts and DNA damage.. Forty patients of age ≥18 years, having recalcitrant genital and/or non-genital warts that persisted for more than 2 years, 40 patients with warts that persisted for <2 years and 40 healthy controls were enrolled in the study. Blood TAS, TOS, OSI, 8-OHdG and dynamic thiol/disulphide homeostasis were evaluated.. Significant differences were detected between the groups in the levels of 8-OHdG, TOS, OSI, total thiol, native thiol, reduced thiol, as well as native thiol/total thiol ratio, disulphide/total thiol ratio and disulphide/native thiol ratio. Compared with the controls, patients with recalcitrant warts had significantly higher levels of 8-OHdG, TOS and OSI levels. Total thiol and native thiol levels were significantly lower in patients with recalcitrant warts compared with patients with warts that persisted for <2 years. Disulphide levels were significantly higher in the latter group of patients compared with patients with recalcitrant warts and controls. Native thiol/total thiol ratio was significantly higher in both patient groups compared with controls whereas disulphide/total thiol and disulphide/native thiol ratios were significantly lower in both patient groups than in controls.. Our findings suggest that impairment of thiol disulphide homeostasis in patients with recalcitrant warts may lead to increased OS and DNA damage. Thus, antioxidant administration with thiol containing proteins may help in the regression of warts and thereby prevent carcinogenesis.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adolescent; Adult; Antioxidants; Chronic Disease; Disulfides; DNA Damage; Female; Homeostasis; Humans; Male; Middle Aged; Oxidants; Oxidative Stress; Sulfhydryl Compounds; Warts; Young Adult

Previous studies demonstrated that urinary 8-oxodG is a predictive biomarker for

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Animals; Anthelmintics; Biomarkers; Cholangiocarcinoma; Chronic Disease; Deoxyguanosine; Female; Fibrosis; Humans; Liver Cirrhosis; Logistic Models; Male; Middle Aged; Opisthorchiasis; Opisthorchis; Praziquantel; Thailand

Chronic inflammation is associated with increased risk of cancer development, whereas the link between chronic inflammation and esophageal carcinogenesis is still obscure heretofore. This study aimed to investigate the relationship between chronic inflammation and DNA damage, as well as the possible role of DNA damage in esophageal carcinogenic process. Endoscopic esophageal biopsies from 109 individuals from Chaoshan littoral, a high-risk region for esophageal squamous cell carcinoma (ESCC), were examined to evaluate the association between chronic inflammation and histological severity, while additional 204 esophageal non-tumor samples from patients with ESCC were collected. Immunohistochemistry was performed to detect the oxidative DNA damage and DNA double-strand breaks (DSBs). Significantly positive correlation was observed between degree of chronic inflammation and esophageal precursor lesions (rs = 0.37, P < 0.01). Immunohistochemical analysis showed that oxidative DNA damage level was positively correlated with the degree of chronic inflammation (rs = 0.21, P < 0.05). Moreover, the level of oxidative DNA damage positively correlated with histological severity (rs = 0.49, P < 0.01). We found that the extent of DSBs was progressively increased with inflammation degree (P < 0.01) and the progression of precancerous lesions (P < 0.001). Collectively, these findings provide evidence linking chronic inflammation-associated genomic instability with esophageal carcinogenesis and suggest possibilities for early detection and intervention of esophageal carcinogenesis.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Carcinogenesis; Carcinoma, Squamous Cell; Chronic Disease; Deoxyguanosine; Disease Progression; DNA Damage; Esophageal Neoplasms; Esophagus; Female; Genomic Instability; Histones; Humans; Immunohistochemistry; Inflammation; Male; Middle Aged

Copper is an essential element for human growth and development; however, excessive intake of copper could contribute to neurotoxicity. Here we show that chronic exposure to copper in drinking water impaired spatial memory with simultaneous selective loss of hippocampal pre-synaptic protein synapsin 1, and post-synaptic density protein (PSD)-93/95 in mice. Copper exposure was shown to elevate the levels of nitrotyrosine and 8-hydroxydeoxyguanosine (8-OHdG) in hippocampus, two markers of oxidative stress. Concurrently, we also found that copper exposure activated double stranded RNA-dependent protein kinase (PKR) as evidenced by increased ratio of phosphorylated PKR at Thr451 and total PKR and increased the phosphorylation of its downstream signaling molecule eukaryotic initiation factor 2α (eIF2α) at Ser51 in hippocampus. Consistent with activation of PKR/eIF2α signaling pathway which was shown to mediate synaptic deficit and cognitive impairment, the levels of activating transcription factor 4 (ATF-4), a downstream signaling molecule of eIF2α and a repressor of CREB-mediated gene expression, were significantly increased, while the activity of cAMP response elements binding protein (CREB) was inactivated as suggested by decreased phosphorylation of CREB at Ser133 by copper exposure. In addition, the expression of the pro-apoptotic target molecule C/EBP homology protein (CHOP) of ATF-4 was upregulated and hippocampal neuronal apoptosis was induced by copper exposure. Taken together, we propose that chronic copper exposure might cause spatial memory impairment, selective loss of synaptic proteins, and neuronal apoptosis through the mechanisms involving activation of PKR/eIF2α signaling pathway.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Activating Transcription Factor 4; Animals; Apoptosis; Chronic Disease; Copper Sulfate; Cyclic AMP Response Element-Binding Protein; Deoxyguanosine; Disks Large Homolog 4 Protein; DNA-Binding Proteins; eIF-2 Kinase; Guanylate Kinases; Hippocampus; Male; Membrane Proteins; Memory Disorders; Mice, Inbred C57BL; Neurons; Oxidative Stress; Random Allocation; Signal Transduction; Spatial Memory; Synapsins; Transcription Factor CHOP; Transcription Factors; Tyrosine

Chronic kidney disease patients share clinical and pathological features with the general aging population. Increased oxidative DNA damage, accumulation of cell cycle-arrested cells and decreased Klotho expression are assumed to be age-related factors that are reportedly linked to kidney disease. This study sought to determine the association between these age-related factors and renal damage in patients with IgA nephropathy (IgAN).. We performed a cross-sectional analysis of 71 patients who were diagnosed with IgAN by renal biopsy. Expression of 8-hydroxydeoxyguanosine (8-OHdG, a marker of oxidative DNA damage), p16 (a marker of cell cycle-arrest) and Klotho (an anti-aging protein) were evaluated by immunohistochemical staining of renal biopsy samples. We correlated the changes in expression of these markers with Lee's pathologic grades and the Oxford classification. We also investigated the independent association between these markers and interstitial fibrosis using multiple linear regression analysis.. 8-OHdG and p16 increased but Klotho decreased with progression of pathologic grade. Expression of 8-OHdG and p16 increased with the deterioration of mesangial hypercellularity and segmental glomerulosclerosis. In addition, p16 increased but Klotho decreased with progression of tubular atrophy/interstitial fibrosis. In univariate regression analysis, age, body mass index, systolic blood pressure, urinary protein excretion and expression of 8-OHdG, p16 and Klotho showed significant correlations with interstitial fibrosis. Multivariable regression analyses revealed that aging, increased renal expression of p16 and decreased expression of Klotho were independently correlated with interstitial fibrosis.. The age-related factors might play important roles in the development of IgAN.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aging; Cell Cycle Checkpoints; Chronic Disease; Cross-Sectional Studies; Cyclin-Dependent Kinase Inhibitor p16; Deoxyguanosine; Disease Progression; Female; Fibrosis; Glomerulonephritis, IGA; Glucuronidase; Humans; Kidney; Klotho Proteins; Male; Middle Aged; Neoplasm Proteins; Young Adult

Previous studies have supported the claim that psychological stress induces the production of reactive oxygen species. Several authors have suggested that patients with psychiatric disorders show high levels of oxidative stress markers. We examined different oxidative stress markers in patients with chronic schizophrenia.. This study included 29 patients with chronic schizophrenia and 30 healthy volunteers. The concentration of urinary biopyrrins and 8-hydroxydeoxyguanosine (8-OHdG), as measured by enzyme-linked immunosorbent assay, were normalized to the urinary concentration of creatinine. Psychiatric symptoms were assessed by the administration of the Brief Psychiatric Rating Scale (BPRS).. The concentration of biopyrrins in patients with chronic schizophrenia was significantly higher when compared with healthy volunteers. The correlation between biopyrrin level and the duration of illness was highly significant. There were no significant differences in the levels of urinary 8-OHdG between the two groups. In schizophrenic patients, the level of urinary biopyrrins showed correlations with BPRS scores, while the level of urinary 8-OHdG did not show correlations with BPRS.. Urinary biopyrrins are increased in patients with chronic schizophrenia while urinary 8-OHdG is not increased. These findings suggest that patients with chronic schizophrenia are under the condition of certain oxidative stresses.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Bilirubin; Biomarkers; Case-Control Studies; Chronic Disease; Deoxyguanosine; Female; Humans; Male; Middle Aged; Oxidative Stress; Schizophrenia

To explore the association between dyslipidemia and the level of 8-OHdG/Cr in urine among a population exposed to chronic arsenic.. Four hundred and seven subjects were randomly selected in an arsenic-affected area in Inner Mongolia. After blood biochemical examination, all the subjects were divided into 4 groups based on the results of total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C)and low density lipoprotein cholesterol (LDL-C). The groups consisted of hypercholesterolemia, HDL-C ratio anomaly, combined hypercholesterolemia and HDL-C ratio anomaly, as well as a normal lipid group. Urine samples were collected and 8-OHdG/Cr was measured using the ELISA method. A generalized linear mixed model was used to analyze the association between dyslipidemia and 8-OHdG/Cr.. The levels of 8-OHdG/Cr as 55.73 (39.90-79.94) ng/mg, 58.08 (44.94-69.91)ng/mg, 65.28 (49.29-92.95) ng/mg and 51.43 (36.86-68.57) ng/mgin the HDL-C ratio anomaly, hypercholesterolemia, combined hypercholesterolemia and HDL-C ratio anomaly groups and the control group, respectively, which showed significant differences on the levels of 8-OHdG/Cr in the four groups(P = 0.006). From the linear regression analysis results showed that the 8-OHdG/Cr level in combined hypercholesterolemia and HDL-C ratio anomaly group was higher (4.25 ± 0.55 ng/mg) than in the control group (3.96 ± 0.55 ng/mg) (P = 0.018). After adjusting for important covariates, there was a linear trend between the levels of 8-OHdG/Cr and dyslipidemia (P = 0.016).. Data from our study showed a linear relation between hypercholesterolemia, HDL-C ratio anomaly and the 8-OHdG/Cr level, suggesting that dyslipidemia was associated with oxidative DNA damage among those .

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adolescent; Adult; Aged; Arsenic Poisoning; Cholesterol, HDL; Chronic Disease; Deoxyguanosine; DNA Damage; Dyslipidemias; Female; Humans; Male; Middle Aged; Triglycerides; Young Adult

Chronic psychological stress appears to accelerate biological aging, and oxidative damage is an important potential mediator of this process. However, the mechanisms by which psychological stress promotes oxidative damage are poorly understood. This study investigates the theory that cortisol increases in response to an acutely stressful event have the potential to either enhance or undermine psychobiological resilience to oxidative damage, depending on the body's prior exposure to chronic psychological stress. In order to achieve a range of chronic stress exposure, forty-eight post-menopausal women were recruited in a case-control design that matched women caring for spouses with dementia (a chronic stress model) with similarly aged control women whose spouses were healthy. Participants completed a questionnaire assessing perceived stress over the previous month and provided fasting blood. Three markers of oxidative damage were assessed: 8-iso-prostaglandin F(2α) (IsoP), lipid peroxidation, 8-hydroxyguanosine (8-oxoG) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), reflecting oxidative damage to RNA/DNA respectively. Within approximately one week, participants completed a standardized acute laboratory stress task while salivary cortisol responses were measured. The increase from 0 to 30 min was defined as "peak" cortisol reactivity, while the increase from 0 to 15 min was defined as "anticipatory" cortisol reactivity, representing a cortisol response that began while preparing for the stress task. Women under chronic stress had higher 8-oxoG, oxidative damage to RNA (p<.01). A moderated mediation model was tested, in which it was hypothesized that heightened anticipatory cortisol reactivity would mediate the relationship between perceived stress and elevated oxidative stress damage, but only among women under chronic stress. Consistent with this model, bootstrapped path analysis found significant indirect paths from perceived stress to 8-oxoG and IsoP (but not 8-OHdG) via anticipatory cortisol reactivity, showing the expected relations among chronically stressed participants (p≤.01) Intriguingly, among those with low chronic stress exposure, moderate (compared to low) levels of perceived stress were associated with reduced levels of oxidative damage. Hence, this study supports the emerging model that chronic stress exposure promotes oxidative damage through frequent and sustained activation of the hypothalamic-pituitary-adrenal axis. It also supports the less

Topics: 8-Hydroxy-2'-Deoxyguanosine; Acute Disease; Affect; Aged; Anticipation, Psychological; Caregivers; Case-Control Studies; Chronic Disease; Deoxyguanosine; Dinoprost; DNA Damage; Female; Guanosine; Humans; Hydrocortisone; Middle Aged; Oxidative Stress; Resilience, Psychological; Saliva; Secretory Rate; Spouses; Stress, Psychological; Surveys and Questionnaires

Cyclosporine A (CsA)-associated oxidative stress has been proposed as an important mechanism of renal injury. This study was designed to examine whether N-acetylcysteine (NAC), a well-known antioxidant, affects Klotho, antiaging gene, expression and its signaling pathway in an experimental model of chronic CsA nephropathy.. Mice maintained on a low-sodium diet were given vehicle (olive oil, 1 mL/kg/day), CsA (30 mg/kg/day), NAC (150 mg/kg/day), or a combination of CsA and NAC for 4 weeks. The effect of NAC on CsA-induced renal injury was evaluated with basic parameters, histopathology, and markers of oxidative stress [8-hydroxy-2'-deoxyguanosine (8-OHdG) excretion and manganese superoxide dismutase (MnSOD) expression]. The influence of NAC on Klotho and its signal pathway (p-AKT and p-FoxO1) in CsA-treated mouse kidney was evaluated with immunohistochemistry and/or immunoblot.. Concomitant administration of CsA and NAC significantly improved renal function and attenuated tubulointerstitial fibrosis, and these changes were accompanied by decreased urinary 8-OHdG level and increased MnSOD expression. NAC treatment preserved Klotho gene expression compared with CsA treatment alone (P < 0.05), and this correlated with urinary 8-OHdG excretion (r = -0.934) and MnSOD expression (r = 0.873, P < 0.001 for both). Concomitant treatment of CsA and NAC translocated FoxO1 from the cytoplasm to the nucleus, implicating dephosphorylation of FoxO1 by NAC in p-AKT/p-FoxO1 pathway.. NAC treatment preserves Klotho expression and modifies p-AKT/p-FoxO1 pathway in chronic CsA nephropathy.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Acetylcysteine; Animals; Antioxidants; Apoptosis; Chronic Disease; Cyclosporine; Deoxyguanosine; Disease Models, Animal; Forkhead Box Protein O1; Forkhead Transcription Factors; Gene Expression; Glucuronidase; Immunosuppressive Agents; Kidney Diseases; Klotho Proteins; Male; Mice; Mice, Inbred ICR; Oxidative Stress; Proto-Oncogene Proteins c-akt; Signal Transduction; Superoxide Dismutase

Aging is commonly defined as the accumulation of diverse deleterious changes in cells and tissues with advancing age. To investigate whether aging changes are involved in the lacrimal glands of chronic graft-versus-host disease (cGVHD) model mice, we obtained the specimens from cGVHD model mice, untreated aged and young mice, and examined by histopathology, and immunoblotting. Oxidative stress markers, 8-OHdG, 4-HNE, and hexonoyl lesion (HEL), and other aging markers, p16 and p38, were used to assess the samples. The infiltrating mononuclear cells and endothelia of capillaries in the cGVHD and aged mice expressed the oxidative stress markers and other aging markers, but not in the young mice. Histological changes and the expression of aging markers in the samples from cGVHD mice exhibited similar features to those in aging mice. These results suggest that changes that typically appear with advanced age occur earlier in the lives of mice with lacrimal gland cGVHD.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aging; Animals; Biomarkers; Chronic Disease; Deoxyguanosine; Disease Models, Animal; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Lacrimal Apparatus; Lipid Peroxidation; Macrophages; Male; Mice; Oxidative Stress; p38 Mitogen-Activated Protein Kinases; Reactive Oxygen Species

In spite of improvement in obstetrical care, pregnancy in women with type 1 diabetes mellitus is associated with increased perinatal morbidity and mortality. Hyperglycemia during pregnancy causes excessive fetal growth and chronic fetal hypoxia as reflected in increased erythropoietin (EPO) levels in amniotic fluid (AF).. We hypothesized that the degree of fetal hypoxia would correlate with fetal oxidative and nitrosative stress as evidenced ty the concentration of specific biomarkers in AF.. 19 pregnant women with type 1 or insulin-treated gestational diabetes mellitus were studied. AF samples were collected and processed for EPO, meta-tyrosine, nitro-tyrosine and 8-hydroxy-2-deoxiguanosine by chemiluminescent immunoassay and high-performance liquid chromatography coupled to tandem mass spectrometry methods, respectively.. The mean (SD) of the last HbA1c concentration before delivery was 7.7% (1.1). Median gestational age was 258 days (range 231-268). Birth weight was 3,868 ± 695 g with a z-score >2 SD in 47% of the cases. A significant correlation was found between the concentrations of AF EPO and meta-tyrosine/phenylalanine ratio (p < 0.001), nitro-tyrosine (p < 0.01) and 8-oxo-dG/2dG ratio (p < 0.001).. We confirmed that fetuses of type 1 diabetes or insulin-treated gestational diabetes pregnancies experience chronic hypoxia as reflected by increased EPO concentrations in AF near term. Moreover, EPO levels significantly correlated with the concentration of oxidative and nitrosative stress biomarkers in AF. This pro-oxidant status may predispose newborn infants to poor postnatal adaptation and early neonatal complications.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Amniocentesis; Amniotic Fluid; Biomarkers; Birth Weight; Chromatography, High Pressure Liquid; Chronic Disease; Deoxyguanosine; Diabetes Mellitus, Type 1; Diabetes, Gestational; Erythropoietin; Female; Fetal Hypoxia; Gestational Age; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Immunoassay; Infant, Newborn; Insulin; Male; Nitrosation; Oxidative Stress; Pilot Projects; Pregnancy; Pregnancy in Diabetics; Tandem Mass Spectrometry; Tyrosine; Young Adult

To further characterize, in a rat model, the effects of atherosclerosis-induced chronic bladder ischemia on bladder function and associated changes in oxidative stress markers and proinflammatory cytokines.. Adult Sprague-Dawley male rats were divided into three groups (arterial endothelial injury: AI, sham, naïve). The AI group (n = 14) underwent endothelial injury of the iliac arteries and received a 2% cholesterol diet. The sham group (n = 12) underwent sham operation and received a 2% cholesterol diet. The naïve group (n = 12) received a regular diet. After 8 weeks, cystometrograms (CMG) without anesthesia or restraint were performed. In bladders from each group, oxidative stress markers (8-hydroxy-2'-deoxyguanosine: 8-OHdG; malondialdehyde: MDA) and proinflammatory cytokines (IL-8 like cytokine CXCL1/CINC-1, TNF-α, IL-6) were quantified. Histological examination of the iliac arteries was also performed.. At 8 weeks, the body and bladder wet weights were not significant different among the three groups. The micturition interval in the AI group decreased significantly compared with those in the other two groups, but maximum pressure during micturition did not change. The iliac arteries in the AI group revealed thickening of intima as well as diffuse media fibrosis at the sites of balloon injury. The levels of oxidative stress markers and proinflammatory cytokines were significantly higher in the AI than in the other groups.. Oxidative stress and inflammation may be key factors in the development of bladder overactivity in atherosclerosis-induced chronic bladder ischemia.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Atherosclerosis; Biomarkers; Chronic Disease; Cytokines; Deoxyguanosine; Disease Models, Animal; Iliac Artery; Ischemia; Male; Malondialdehyde; Oxidative Stress; Rats; Rats, Sprague-Dawley; Up-Regulation; Urinary Bladder; Urinary Bladder, Overactive; Urination; Urodynamics

The authors recently reported that urinary 8-hydroxy-2'-deoxyguanosine (U8-OHdG) derived from cardiac tissue reflects clinical status and cardiac dysfunction severity in patients with chronic heart failure (CHF). The aim of the present study was to investigate whether U8-OHdG levels can accurately predict cardiac events in CHF patients and their response to β-blocker treatment.. Plasma brain natriuretic peptide (BNP) and U8-OHdG levels were measured in 186 consecutive CHF patients before discharge. Patients were then prospectively followed (median follow-up, 649 days) with endpoints of cardiac death or hospitalization due to progressive heart failure. From receiver operating characteristic curve analysis, cut-offs were 12.4ng/mg creatinine (Cr) for U8-OHdG and 207pg/ml for BNP. On multivariate Cox analysis, U8-OHdG and BNP were independent predictors of cardiac events. Patients were classified into 4 groups according to U8-OHdG and BNP cut-offs. The hazard ratio for cardiac events in patients with BNP ≥207pg/ml and U8-OHdG ≥12.4ng/mg Cr was 16.2 compared with approximately 4 for patients with only 1 indicator above its respective cut-off. Furthermore, carvedilol therapy was initiated in 30 CHF patients. In responders (≥10% increase in left ventricular ejection fraction [LVEF] or ≥1 class decrease in New York Heart Association [NYHA] class), U8-OHdG levels decreased significantly along with improved NYHA class, LVEF, and BNP levels after treatment.. U8-OHdG may be a useful biomarker for predicting cardiac events and evaluating β-blocker therapy effectiveness in CHF patients.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adrenergic beta-Antagonists; Adult; Aged; Biomarkers; Carbazoles; Carvedilol; Chronic Disease; Death, Sudden, Cardiac; Deoxyguanosine; Female; Follow-Up Studies; Heart Failure, Systolic; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Propanolamines; Prospective Studies; Risk Factors; Treatment Outcome

8-hydroxydeoxyguanosine (8-OHdG) is commonly used as a marker to evaluate oxidative DNA damage in disorders including chronic inflammatory diseases such as inflammatory periodontal pathologies. In the current study we hypothesized that the level of 8-OHdG in saliva increases by the periodontal destruction severity determined by clinical parameters as clinical attachment level (CAL).. A cross-sectional study was conducted on a sum of 60 age gender balanced; chronic periodontitis (CP) (n=20), chronic gingivitis (CG) (n=20) and healthy (H) (n=20) individuals. Clinical periodontal parameters and salivary 8-OHdG levels were evaluated.. The mean 8-OHdG level in the saliva of the CP group was significantly higher than H and CG groups (p< 0.001). Statistically significant correlation was only observed between the salivary levels of 8-OHdG and age (p< 0.05), probing depth (PD) and CAL (p< 0.001) in CP group. However, when CP patients were classified according to their CAL levels (CAL⩾ 3 mm (n=11) and CAL<3 mm (n=9)) statistically significant correlation was only observed between the salivary levels of 8-OHdG and CAL ⩾ 3 mm patients (p< 0.001).. We suggest that elevated salivary levels of 8-OHdG may be a marker for disease activity and it may reflect indirectly disease severity parameters such as CAL.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Case-Control Studies; Chronic Disease; Chronic Periodontitis; Cross-Sectional Studies; Deoxyguanosine; DNA Damage; Enzyme-Linked Immunosorbent Assay; Female; Gingivitis; Humans; Male; Middle Aged; Oxidative Stress; Periodontal Index; Saliva

Increased production of reactive oxygen species, which cause oxidative DNA damage, is considered to be related to gastric carcinogenesis. The aim of this research was to detect the 8-OHdG and the expression of hOGG1and MnSOD, in human gastric mucosa with chronic atrophic gastritis (CAG) and gastric carcinoma (GC) comparing with normal controls (NC).. The level of 8-OHdG in gastric biopsy specimens was assessed with immunohistochemistry. The expression level of hOGG1and MnSOD in gastric tissues was assessed with Western blot.. The 8-OHdG staining in CAG and GC mucosa was stronger than control (p<0.01). hOGG1 was expressed to a lower degree in GC and CAG when compared to the control group (both p<0.01) and the level of GC was even lower than CAG (p<0.05). MnSOD was expressed to a greater degree in GC group when compared to the control (p<0.05).. CAG patients who express 8-OHdG highly should be monitored for the potentially occurrence of GC. The lower lever of hOGG1 in CAG and GC with higher level of 8-OHdG implies that hOGG1 is closely related to oxidative DNA damage and may lead to carcinoma. The increasing expression of MnSOD in the gastric mucosa may indicate the occurrence of gastric cancer.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers, Tumor; Biopsy; Blotting, Western; Case-Control Studies; China; Chronic Disease; Deoxyguanosine; DNA Damage; DNA Glycosylases; DNA Repair; Female; Gastric Mucosa; Gastritis, Atrophic; Humans; Immunohistochemistry; Male; Middle Aged; Oxidative Stress; Stomach Neoplasms; Superoxide Dismutase

Iron metabolism is an important factor of anemia in chronic kidney disease (CKD). Hepcidin is a regulator of iron homeostasis and has a major role in the anemia of chronic disease (ACD). Oxidative stress (OS) is also associated with iron metabolism. However, the clinical utility of hepcidin, especially its association with OS, in CKD patients not receiving dialysis is still unclear.. We recruited 117 patients (62 ± 15 years, 85 males, and median estimated glomerular filtration rate (eGFR) 22 ml/min/1.73 m2) with CKD not receiving dialysis. Serum 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of DNA oxidative injury, and serum hepcidin-25 were measured by ELISA and by liquid chromatography tandem mass spectrometry, respectively.. Hepcidin-25 was associated positively with ferritin, high-sensitive C-reactive protein (hsCRP) and 8-OHdG, and negatively with eGFR and hemoglobin. Sex, oral iron, hemoglobin, transferrin saturation (TSAT), ferritin, and hsCRP were independently associated with hepcidin-25 in a multiple regression model. In contrast, neither eGFR nor 8-OHdG independently affected hepcidin- 25.. The close association between hepcidin and serum ferritin, oral iron and hsCRP indicates that it plays a key role in the pathogenesis of anemia in patients with CKD not receiving dialysis. In contrast, effects of eGFR and OS were not apparent.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Antimicrobial Cationic Peptides; C-Reactive Protein; Chronic Disease; Deoxyguanosine; Erythropoietin; Female; Hepcidins; Humans; Kidney Diseases; Male; Middle Aged; Oxidative Stress; Renal Dialysis

The Klotho gene plays a role in suppressing ageing-related disorders. It is suggested that activation of renin-angiotensin system (RAS) or oxidative stress suppresses Klotho in the kidney. This study evaluated the association between Klotho expression and RAS in cyclosporine (CsA)-induced renal injury.. Chronic CsA nephropathy was induced by administering CsA (30 mg/kg) to mice on a low-salt diet (LSD) for 4 weeks. A normal-salt diet (NSD) was used as the control. Reverse transcription-polymerase chain reaction, western blot and immunohistochemistry were performed for Klotho and intrarenal RAS activity was measured using immunohistochemistry for angiotensinogen and renin. Oxidative stress was measured with urinary excretion of 8-hydroxy-2'-deoxyguanosine (8-OHdG).. CsA treatment decreased Klotho mRNA and protein in mouse kidney in a dose-dependent and time-dependent manner, but a concurrent treatment with losartan, an angiotensin II type 1 (AT1) receptor blocker, reversed the decrease in Klotho expression with histological improvement. This finding was more marked in the LSD than the NSD. Klotho expression was correlated with angiotensinogen and renin expression, tubulointerstitial fibrosis score and urinary 8-OHdG excretion.. Angiotensin II may play a pivotal role in regulating Klotho expression in CsA-induced renal injury. AT1 receptor blocker may inhibit the ageing process by decreasing oxidative stress caused by CsA.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aging; Angiotensin II; Animals; Blotting, Western; Chronic Disease; Cyclosporine; Deoxyguanosine; Disease Models, Animal; Glucuronidase; Immunoenzyme Techniques; Immunosuppressive Agents; Kidney Diseases; Klotho Proteins; Male; Mice; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Up-Regulation; Vasoconstrictor Agents

The purpose of this study was to explore the bioavailability, efficacy and molecular mechanisms of green tea polyphenols (GTP) related to preventing bone loss in rats with chronic inflammation. A 2 [placebo vs. lipopolysaccharide (LPS)]×2 (no GTP vs. 0.5% GTP in drinking water) factorial design enabled the evaluation of effects of LPS administration, GTP levels, and LPS×GTP interaction. Urinary GTP components and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were determined by high-pressure liquid chromatography for bioavailability and molecular mechanism, respectively. Efficacy was evaluated by examining changes in femoral mineral content (BMC) and density (BMD) using dual-energy X-ray absorptiometry, and bone turnover biomarkers [osteocalcin (OC) and tartrate-resistant acid phosphatase (TRAP)] using respective ELISA kits. The mRNA expression of tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2) in spleen was determined by real-time RT-PCR. Neither LPS administration nor GTP levels affected body weight and femoral bone area throughout the study period. Only GTP supplementation resulted in increased urinary epigallocatechin and epicatechin concentrations. LPS administration led to a decrease in femur BMC and BMD, and serum OC levels, but an increase in serum TRAP, urinary 8-OHdG and spleen mRNA expression of TNF-α and COX-2 levels. GTP supplementation resulted in higher values for femur BMC, BMD and serum OC, but lower values for serum TRAP, urinary 8-OHdG and spleen mRNA expression of TNF-α and COX-2 levels. We conclude that GTP mitigates bone loss in a chronic inflammation-induced bone loss model by reducing oxidative stress-induced damage and inflammation.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Base Sequence; Biological Availability; Body Weight; Bone Diseases, Metabolic; Bone Remodeling; Chromatography, High Pressure Liquid; Chronic Disease; Cyclooxygenase 2; Deoxyguanosine; Disease Models, Animal; DNA Primers; Drinking Behavior; Enzyme-Linked Immunosorbent Assay; Female; Flavonoids; Inflammation; Phenols; Polyphenols; Rats; RNA, Messenger; Tea; Tumor Necrosis Factor-alpha

Helicobacter pylori (H pylori) infection induces chronic inflammation that can progress to gastric atrophy, intestinal metaplasia, and gastric adenocarcinoma. We have examined oxidative damage caused by Helicobacter pylori, metaplasia, and atrophy of gastric mucosal cells in patients with chronic gastritis by measuring their urinary 8-hydroxydeoxyguanosine (8-OHdG) levels.. We recruited 77 outpatients with chronic gastritis, confirmed by endoscopic examination. H pylori status was evaluated by histology (modified Giemsa staining), the H pylori stool antigen test (n=20), and the 13C urea breath test (n=27), as described in the Maastricht consensus report.. The mean amount of 8-OHdG (microg/g creatinine) in 77 subjects was 18.07 +/- 13.49 x 10(-3) microg/g creatinine. The levels of urinary 8-OHdG in the H pylori-positive gastritis patients were also significantly higher than those in the H pylori-negative gastritis patients (P=0.003, respectively, 20.42 +/- 13.33 x 10(-3) microg/g creatinine, 13.16 +/- 12.71 x 10(-3) microg/g creatinine). The level of urinary 8-OHdG was markedly higher in patients with gastric atrophy and intestinal metaplasia than in those without (P=0.000, P=0.002, respectively). There were significant correlations between levels of urinary 8-OHdG and both the atrophy score (r=0.441, P=0.000) and the intestinal metaplasia score (r=0.436, P=0.000).. Urinary 8-OHdG levels could be investigated in every patient with chronic gastritis, since it is a simple and completely noninvasive procedure. In patients with high levels of urinary 8-OHdG, endoscopic procedures or even pathological investigation may then be carried out, with the consideration that there is a high risk of intestinal metaplasia or atrophy.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Atrophy; Chronic Disease; Deoxyguanosine; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Intestinal Mucosa; Male; Metaplasia; Middle Aged; Prospective Studies

Salt intake not only elevates the levels of blood pressure, glomerular capillary pressure and proteinuria, but also increases oxidative stress within the renal cortex in animal models. We examined the effect of salt intake on the rate of renal function decline, urinary protein and oxidative stress in patients with chronic kidney disease (CKD).. Clinical data including systolic blood pressure (SBP)and diastolic blood pressure (DBP), serum creatinine, uric acid, total cholesterol, triglyceride, urinary protein, salt intake, protein intake of non-diabetic CKD 53 patients were observed for one year. At the end of the observation period, we measured 8-hydroxydeoxy guanosine (8-OHdG) in spot urine. We calculated the slope of reciprocal serum creatinine as the rate of renal function decline (delta1/Cr). We then investigated the relationship between those clinical factors and delta1/Cr, and urinary 8-OHdG, and also selected clinical factors that significantly influence delta1/Cr and urinary 8-OHdG by stepwise multiple regression analysis. In addition, we investigated the gender difference in urinary 8-OHdG.. Annual mean SBP and DBP of all patients were 121.5 +/- 9.3 mmHg and 72.5+/- 6.2 mmHg, respectively. delta1/Cr was negatively correlated with salt intake, urinary protein and urinary protein was a significant predictor of delta1/Cr in a multiple regression analysis. Salt intake was positively correlated with protein intake and urinary protein. Urinary 8-OHdG of all patients was positively correlated with urinary protein and it was a significant predictor. Urinary 8-OHdG of male patients was positively correlated with salt intake and was a significant predictor; in female patients, it was positively correlated with urinary protein and total cholesterol and these two factors were significant predictors.. Salt intake increases urinary protein and promotes the progression of renal failure in CKD patients.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Biomarkers; Chronic Disease; Deoxyguanosine; Disease Progression; Humans; Kidney Diseases; Male; Middle Aged; Oxidative Stress; Proteinuria; Regression Analysis; Renal Insufficiency; Sodium Chloride, Dietary

Genetic instability is a hallmark of human cancers. It is the driving force for tumor development as it facilitates the accumulation of mutations in genes that regulate cell death and proliferation and therefore promotes malignant transformation. Chronic inflammation is a common underlying condition for human tumor development, accounting for approximately 20% of human cancers. TNFalpha is an important inflammation cytokine and is crucial to the development of inflammation-associated cancers. We have shown that TNFalpha can cause DNA damages through reactive oxygen species (ROS). TNFalpha treatment in cultured cells resulted in increased gene mutations, gene amplification, micronuclei formation and chromosomal instability. Antioxidants significantly reduced TNFalpha-induced genetic damage. In addition, TNFalpha treatment alone led to increased malignant transformation of mouse embryo fibroblasts, which could be partially suppressed by antioxidants. Therefore, genetic instability plays an important role in inflammation-associated cancers.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Cell Transformation, Neoplastic; Cells, Cultured; Chromosomal Instability; Chromosome Aberrations; Chronic Disease; Colonic Neoplasms; Deoxyguanosine; Embryo, Mammalian; Fibroblasts; Humans; In Situ Hybridization, Fluorescence; Inflammation; Mice; Mice, Inbred BALB C; Mice, Nude; Micronucleus Tests; Reactive Oxygen Species; Tumor Necrosis Factor-alpha

Hypoxia is a predictor of poor patient survival in several cancers, including breast carcinomas. One possible mechanism is genomic instability induced by oxic stress. In this study we examined this possible mechanism by exposing an in vivo breast cancer model to hypoxia/reoxygenation. MMTV-Neu transgenic mice were exposed to cycling acute (AH) or chronic hypoxia (CH) before (early) or after (late) tumour detection to study effects of hypoxia on tumour initiation and progression, respectively. We observed no effect of the hypoxic exposures on times to first tumour detection, but we saw a trend of early AH-exposed mice to develop more tumours and macrometastases than CH-exposed mice. Unexpectedly, but consistent with these findings, we observed significantly reduced 8-oxo-dG lesions levels in the mammary tissue with the greatest difference observed between the air control (AC) and AH-exposed groups. In the late gassing group, there was a similar trend for reduced 8-oxo-dG lesion levels, but interestingly mice that developed macroscopic lung metastases demonstrated significantly increased levels of 8-oxo-dG lesions in their tumours relative to those that did not, irrespective of the gassing exposure. A trend for increased macrophage content was observed in tumours from mice exposed to acute hypoxia. Our results indicate that oxic stress induced by hypoxia/reoxygenation is unlikely to be a major factor driving tumour progression of established MMTV-Neu tumours but suggest that acute and chronic hypoxia may affect tumour incidence and metastasis when applied prior to tumour development.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Acute Disease; Animals; Breast Neoplasms; Cell Hypoxia; Chronic Disease; Deoxyguanosine; Disease Progression; DNA Primers; DNA, Neoplasm; Female; Humans; Hypoxia; Mice; Mice, Transgenic; Neoplasm Metastasis; Receptor, ErbB-2

In order to evaluate the chronic effect of polymerized toner particles on the lung, inflammation- and fibrosis-related genes were analyzed and 8-hydroxydeoxyguanosine (8-OHdG) was examined by using the lung tissue of rats subjected to 24 months of toner inhalation exposure. Wistar female rats were divided into four groups (5 weeks old, 30 rats in each): the high concentration exposure group (16.3 +/- 0.6 mg/m(3)), the medium concentration exposure group (4.4 +/- 0.3 mg/m(3)), the low concentration exposure group (1.6 +/- 0.2 mg/m(3)), and the control group (clean air). The material used was black toner, and its aerodynamic diameter in the exposure chamber was 3.0 microm. The rats were exposed to the material for 24 months (6 hours/day, 5 days/week) and dissected after the exposure period. RNA was extracted from one lung and the gene expression related to inflammation and fibrosis. Matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2), and type I collagen were analyzed according to the ratio of each gene/beta-actin. Also, 8-OHdG level in the lung tissue was measured by HPLC with an electrochemical detector. Small fibrotic foci were found in the toner exposed groups; however, progressive or irreversible fibrosis was not found. The incidence of small fibrotic foci and cell aggregation increased in a dose-dependent manner. There were no significant differences of expression of MMP-2, TIMP-2, and type I collagen between the control group and each exposed group. Lung tumors did not develop in each group. A significant production of 8-OHdG was not observed in the toner exposed groups. In conclusion, toner produced by polymerization was not associated with evidence of carcinogenesis in this experiment.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Chronic Disease; Collagen Type I; Deoxyguanosine; DNA, Complementary; Female; Inhalation Exposure; Ink; Lung; Matrix Metalloproteinase 2; Organ Size; Polymers; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA; Survival Analysis; Tissue Inhibitor of Metalloproteinase-2

To examine whether markers of oxidative stress differ as a function of Type D personality, depression, and chronic heart failure (CHF) etiology. Type D (distressed) personality and depression are related to poor cardiac prognosis. Because patients with CHF are characterized by increased oxidative stress, this may be a candidate mechanism responsible for the adverse prognosis in emotionally distressed patients with CHF.. Serum levels of xanthine oxidase (XO), inducible heat shock protein (Hsp)70, and deoxyribonucleic acid damage marker 8-OHdG were measured in 122 patients, and effects of Type D, depression, and etiology were assessed.. CHF patients with Type D personality had lower levels of Hsp70 than non-Type D patients (6.48 ng/mL versus 7.85 ng/mL, p = .04, d = 0.26), and in case of an ischemic etiology, higher levels of XO (13.57 ng/mL versus 9.84 ng/mL, p = .01, d = 0.98). There were no significant univariate differences for depression. When adding depression as an additional independent variable in the Type D analysis, the effect of Type D personality remained significant (F = 5.460, p = .02) and was independent of depression (F = 0.942, p = .33). The ratio of XO to Hsp70 was significantly higher in Type D patients with CHF as compared with non-Type D patients (6.14 versus 2.83, p = .03, d = 0.39), independent of etiology class.. CHF patients with Type D personality are characterized by an increased oxidative stress burden, apparent in the decreased antioxidant levels and an increased oxidative stress ratio.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Biomarkers; Chronic Disease; Comorbidity; Deoxyguanosine; Depressive Disorder, Major; DNA Damage; Enzyme-Linked Immunosorbent Assay; Female; Health Status; Heart Failure; HSP72 Heat-Shock Proteins; Humans; Male; Myocardial Infarction; Oxidative Stress; Personality; Personality Inventory; Risk Factors; Stress, Psychological; Xanthine Oxidase

The aim of this study was to contribute to the knowledge concerning pathogenesis of inflammatory chronic prostatitis by revealing possible shifts in the balance of markers of oxidative stress and anti-oxidative activity in case of leucocytospermic prostatitis. We also attempted to identify possible relations between seminal micro-organisms and oxidative stress parameters. A many-sided complex of local (spermatozoa, seminal plasma) and general (blood, urine) markers in 21 prostatitis patients and nine controls was compared. In both spermatozoa and seminal plasma, the content of diene conjugates was significantly higher in prostatitis patients compared with healthy controls. At the same time total anti-oxidative status in spermatozoa and total anti-oxidative activity in seminal plasma were lower in prostatitis patients than in controls. In urine, the level of 8-isoprostanes was significantly higher in prostatitis patients than in healthy controls, correlating well with 8-hydroxy-2'-deoxyguanosine. The latter correlated with cellular Fe and Ni contents as well, confirming that these metals with varying valency may cause DNA damage. Reduced glutathione showed higher levels in blood of controls than in prostatitis patients. Coryneform bacteria appeared to be associated with prostatitis-related oxidative stress. In conclusion, leucocytospermic prostatitis patients are characterised by oxidative stress at all levels: systemic (general), seminal plasma and cellular.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Ascorbic Acid; Case-Control Studies; Chronic Disease; Corynebacterium; Deoxyguanosine; Dinoprost; Glutathione; Humans; Interleukin-6; Leukocytes; Male; Metals; Oxidation-Reduction; Oxidative Stress; Prospective Studies; Prostatitis; Reactive Oxygen Species; Semen; Spermatozoa

Heme oxygenase-1 (HO-1), a rate-limiting enzyme in heme catabolism, has antioxidative, antiapoptotic, and antiinflammatory activities. We examined whether HO-1 might be involved in silicosis.. To investigate whether HO-1 can reduce silicosis in mice and humans.. Silicosis was studied using a murine model, and in 46 male patients. Serum HO-1 and 8-hydroxydeoxyguanosine (a marker of oxidative stress) were measured by enzyme-linked immunosorbent assay. Levels of HO-1 were measured by immunohistochemistry and immunoblotting.. Serum HO-1 levels were significantly elevated in patients with silicosis compared with age-matched control subjects or patients with chronic obstructive pulmonary disease. Serum HO-1 levels also correlated inversely with serum 8-hydroxydeoxyguanosine levels and positively with vital capacity and forced expiratory volume in one second in patients with silicosis. HO-1 was present in the lungs of humans and mice with silicosis, especially at sites of silica particle deposition. In mice, silica exposure was associated with acute leukocyte infiltration, leading to development of silicotic lung lesions. The inflammation was suppressed by treatment with hemin, an inducer of HO-1, and enhanced by zinc protoporphyrin, an inhibitor of HO-1.. Pulmonary HO-1 expression is increased in silicosis. HO-1 suppresses reactive oxygen species activity, and subsequent pathologic changes, thereby attenuating disease progression.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aged; Aged, 80 and over; Animals; Biomarkers; Chronic Disease; Deoxyguanosine; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Heme Oxygenase-1; Humans; Immunohistochemistry; Male; Mice; Mice, Inbred BALB C; Middle Aged; Oxidative Stress; Prognosis; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index; Silicosis

Although oxidative stress mediated by reactive oxygen species plays an important role in the pathogenesis of heart failure (HF), good clinical markers for reactive oxygen species in patients with HF have not been established. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) is formed from deoxyguanosine in DNA by hydroxyl free radicals and might serve as a sensitive biomarker of intracellular oxidative stress in vivo. Thioredoxin (TRX) is known to be induced in cells as a radical scavenger against oxidative stress. The aim of this study is to evaluate the clinical significance of the serum 8-OHdG and TRX of patients with chronic HF with idiopathic dilated cardiomyopathy (DCM).. We estimated serum 8-OHdG and TRX levels using enzyme-linked immunosorbent assay in 32 patients with DCM and investigated the impact of these markers to the clinical characteristics of these patients. Serum levels of 8-OHdG, but not TRX were significantly correlated with New York Heart Association functional class, left atrial diameters, left ventricular end-diastolic diameters, left ventricular end-systolic diameters, and plasma levels of brain natriuretic peptide.. These data suggest oxidative DNA damage is increased in patients with DCM according to the severity of HF. Serum levels of 8-OHdG may represent clinically useful markers of left ventricular remodeling.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Cardiac Output, Low; Cardiomyopathy, Dilated; Chronic Disease; Deoxyguanosine; Echocardiography; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Oxidative Stress; Severity of Illness Index; Thioredoxins

The aim of this study was to determine the association between levels of a marker of oxidative stress, 8-hydroxydeoxyguanosine (8-OHdG), in saliva and the presence of teeth with a hopeless prognosis as a result of advanced periodontitis. Thirty-four periodontitis patients were divided into two groups based on the presence or absence of periodontally-involved teeth of hopeless prognosis. Salivary levels of 8-OHdG in those with were significantly higher than in subjects without periodontally-involved teeth of hopeless prognosis (4.78 +/- 0.14 ng/ml and 2.35 +/- 0.18 ng/ml, respectively). We also evaluated 8-OHdG levels in gingival crevicular fluid (GCF) of teeth with advanced periodontal destruction (mean probing depth = 7.2). In this case, 8-OHdG was detected only from those periodontally-involved teeth of hopeless prognosis, and only in some cases (8 out of 18 samples). These data suggest that periodontally-involved teeth of hopeless prognosis are a major source of salivary 8-OHdG. Measurement of salivary 8-OHdG levels may prove to be useful in identifying patients with teeth of hopeless prognosis.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Alveolar Bone Loss; Biomarkers; Case-Control Studies; Chronic Disease; Deoxyguanosine; Disease Progression; Female; Gingival Crevicular Fluid; Humans; Male; Middle Aged; Oxidative Stress; Periodontitis; Prognosis; Saliva; Statistics, Nonparametric

Oxidative stress caused by chronic lung inflammation in patients with cystic fibrosis (CF) and chronic lung infection with Pseudomonas aeruginosa is characterized by the reactive oxygen species (ROS) liberated by polymorphonuclear leukocytes (PMNs). We formulated the hypothesis that oxidation of the bacterial DNA by ROS presents an increased risk for the occurrence of hypermutable P. aeruginosa. The occurrence of hypermutable P. aeruginosa isolates was investigated directly in the sputum of 79 CF patients and among 141 isolates collected from 11 CF patients (10 to 15 isolates/patient) collected from the 1st and up to the 25th year of their chronic lung infection. The level of oxidized guanine moiety 8-oxo-2'-deoxyguanosine (8-oxodG), which is a frequently investigated DNA oxidative lesion, was measured. Hypermutable P. aeruginosa isolates were found in the sputum bacterial population of 54.4% of the CF patients. The earliest mutator P. aeruginosa isolates were found after 5 years from the onset of the chronic lung infection, and once they were present in the CF lung, the prevalence increased with time. The hypermutable isolates were significantly more resistant to antipseudomonal antibiotics than nonhypermutable isolates (P

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Anti-Bacterial Agents; Chronic Disease; Cross-Sectional Studies; Cystic Fibrosis; Deoxyguanosine; Drug Resistance, Bacterial; Humans; Inflammation; Lung Diseases; Mutation; Oxidative Stress; Pseudomonas aeruginosa; Pseudomonas Infections; Sputum

Urinary 8-hydroxy-2'-deoxyguanosin(8-OHdG) has been reported as sensitive biomarker of oxidative DNA damage and also of oxidative stress. We measured the urinary 8-OHdG in patients with chronic liver diseases by competitive ELISA, and analyzed the relationship with clinical characteristics. Fifty patients (male/female: 22/28) with chronic liver disease were enrolled this study. The mean concentration of urinary 8-OHdG in healthy control and patients with liver cirrhosis, chronic hepatitis C, chronic hepatitis B, and autoimmune hepatitis were 10.40+/-3.14, 10.14+/-4.19, 11.79+/-5.58, 14.99+/-4.46, and 13.64+/-3.84 microg/gCr, respectively. There were no significant differences among the five group. The mean concentration of urinary 8-OHdG in inveterate drinker was significantly higher than that in non-drinker (16.67+/-4.29 vs. 11.19+/-4.80 microg/gCr, p<0.05). The smoking enhanced the elevation of urinary 8-OHdG in drinkers. In clinical characteristics, serum y-GTP, a marker of alcoholic liver disease, had significant positive correlation with urinary 8-OHdG on the drinker with chronic hepatitis. In addition, there was a positive correlation between serum ferritin levels and urinary 8-OHdG levels. Iron in the liver suggested oxidative damage of hepatocytes through the fenton reaction in patients with chronic liver disease. In conclusion, drinking and smoking induced liver damage by oxidative stress, and urinary 8-OHdG may be reliable marker of oxidative stress in patients with chronic liver disease.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Alcohol Drinking; Biomarkers; Chronic Disease; Deoxyguanosine; DNA Damage; Enzyme-Linked Immunosorbent Assay; Female; Ferritins; gamma-Glutamyltransferase; Humans; Liver Diseases; Male; Middle Aged; Oxidative Stress; Smoking

We evaluated the effects of chronic hyperglycemia on L5 dorsal root ganglion (DRG) neurons using immunohistochemical and electrophysiologic techniques for evidence of oxidative injury. Experimental diabetic neuropathy was induced by streptozotocin. To evaluate the pathogenesis of the neuropathy, we studied peripheral nerve after 1, 3, and 12 months of diabetes. Electrophysiologic abnormalities were present from the first month and persisted over 12 months. 8-Hydroxy-2'-deoxyguanosine labeling was significantly increased at all time points in DRG neurons, indicating oxidative injury. Caspase-3 labeling was significantly increased at all three time points, indicating commitment to the efferent limb of the apoptotic pathway. Apoptosis was confirmed by a significant increase in the percentage of neurons undergoing apoptosis at 1 month (8%), 3 months (7%), and 12 months (11%). These findings support the concept that oxidative stress leads to oxidative injury of DRG neurons, with mitochondrium as a specific target, leading to impaired mitochondrial function and apoptosis, manifested clinically as a predominantly sensory neuropathy.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Apoptosis; Caspase 3; Caspases; Chronic Disease; Deoxyguanosine; Diabetic Neuropathies; Electrophysiology; Ganglia, Spinal; Histocytochemistry; In Situ Nick-End Labeling; Male; Neurons; Oxidative Stress; Rats; Rats, Sprague-Dawley

We have shown recently that selegiline exerts a cardiac neuroprotective effect in chronic heart failure. Since selegiline has an antioxidant antiapoptotic effect, we proposed to determine whether selegiline attenuates cardiac oxidative stress and myocyte apoptosis in chronic heart failure by modulating Bcl-2 and Bax protein expression, and whether the effects are associated with the improvement of cardiac function. Rabbits with rapid cardiac pacing (360 beats/min) and sham operation without pacing were randomized to receive oral selegiline (1 mg/day) or placebo for 8 weeks. Echocardiography was used to measure left ventricular fractional shortening. After 8 weeks of treatment, animals were studied for arterial norepinephrine and left ventricular systolic function (fractional shortening and dP/dt), and were then sacrificed for measuring the stable oxidative product of myocardial mitochondrial DNA (mtDNA) 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG), myocyte apoptosis by monoclonal antibody to single stranded DNA, and Bcl-2 and Bax protein expression by Western blot and immunohistochemistry. Rapid cardiac pacing increased plasma norepinephrine, cardiac oxidative stress and myocyte apoptosis, reduced Bcl-2 and the Bcl-2 to Bax ratio. These changes were associated with decreased left ventricular fractional shortening and dP/dt. Selegiline treatment in chronic heart failure animals reduced plasma norepinephrine, cardiac oxidative stress and myocyte apoptosis, prevented the changes of Bcl-2 and Bcl-2 to Bax ratio, and improved left ventricular fractional shortening and dP/dt. The findings suggest that the reduction by selegiline of myocyte apoptosis is related to the decrease of cardiac oxidative stress and the modulation of apoptotic and antiapoptotic proteins. The antioxidant antiapoptotic effects of selegiline are potentially beneficial in the improvement of cardiac function in chronic heart failure.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Apoptosis; bcl-2-Associated X Protein; Blotting, Western; Chronic Disease; Deoxyguanosine; Heart Failure; Heart Ventricles; Hemodynamics; Immunohistochemistry; Mitochondria, Heart; Neuroprotective Agents; Norepinephrine; Oxidative Stress; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Rabbits; Selegiline

The enduring cognitive and sensorimotor deficits that result from traumatic brain injury (TBI) are associated with metabolic stress and free radical cascades, which establish conditions that may promote mitochondrial DNA (mtDNA) deletion and oxidation, often observed as a consequence of normal aging. Without substantial mtDNA repair mechanisms, permanent alterations to essential mitochondrial enzymes could perpetuate post-injury pathologic cascades. To determine whether mitochondria from the injured cortex and hippocampus sustain mtDNA damage after TBI, we evaluated mtDNA deletion and oxidation following lateral fluid percussion TBI in the anesthetized adult Sprague-Dawley rat (4 months) compared with uninjured adult and aged rats (n = 4/group). The presence of the 4.8-KB common deletion in mtDNA was assessed by conventional PCR to generate products representing total, non-deleted wild-type, and deleted mtDNA in homogenized tissue and isolated mitochondria 3 and 14 days following TBI. Total and wild-type mtDNA amplification products were obtained from cortical and hippocampal tissue and mitochondria for all conditions. Although no mtDNA deletions were observed following experimental TBI, mtDNA deletion was detected in cortical tissue, but not isolated mitochondria, of naive, aged (24 months) Sprague-Dawley rats, suggesting that the isolation protocol may exclude mitochondria harboring mtDNA damage. Oxidative mtDNA damage in isolated mitochondria assayed by ELISA for 8-hydroxy-2'-deoxyguanosine (8-OHdG) from cortical (0.50 +/- 0.08 pg 8-OHdG/ micro g mitochondria) and hippocampal (0.35 +/- 0.02) regions were unaffected by TBI. However, mitochondrial protein yields from injured and aged brains were comparable and significantly lower than uninjured brain, suggesting that the underlying pathology between TBI and aging may be similar.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aging; Animals; Brain; Brain Injuries; Cerebral Cortex; Chronic Disease; Deoxyguanosine; DNA Damage; DNA, Mitochondrial; Gene Deletion; Hippocampus; Male; Mitochondria; Nerve Tissue Proteins; Polymerase Chain Reaction; Rats; Rats, Sprague-Dawley; Reference Values; Wounds, Nonpenetrating

Reactive oxygen species may be involved in the progression of chronic liver disease and the occurrence of hepatocellular carcinoma (HCC). To clarify whether clinicopathological findings in liver diseases are related to oxidative DNA damage, hepatic expression of the 8-hydroxy-2'-deoxyguanosine (8-OHdG) was examined in 75 liver disease patients, which included 32 chronic hepatitis (CH), 13 liver cirrhosis (LC) and 30 HCC patients. The CH patients had higher 8-OHdG-positive hepatocytes than LC (P < 0.05). In CH and LC, the number of 8-OHdG-positive hepatocytes was correlated with alanine aminotransferase and asparate aminotransferase (P < 0.01 and P < 0.05, respectively). Of 30 HCC cases, 25 cases (83%) showed stronger immunoreactivity than non-cancerous counterparts. The patients with poorly differentiated HCC had a larger tumor size and higher levels of AFP, and exhibited higher labeling indices of PCNA-, TUNEL- and 8-OHdG-positive cells than those with well and moderately differentiated HCC. Our findings suggest that oxidative DNA damage is increased in association with necroinflammation in chronic liver disease and determination of 8-OHdG is useful in assessing high-grade malignancy in HCC.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers, Tumor; Carcinoma, Hepatocellular; Chronic Disease; Deoxyguanosine; DNA Damage; Female; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Reactive Oxygen Species

We determined whether base and nucleotide excision repair is activated in bladder urothelium by chronic persistent low doses of ionizing radiation in male patients with benign prostate hyperplasia and females with chronic cystitis living more than 15 years in Cs contaminated areas after the Chernobyl accident in Ukraine.. Bladder urothelial biopsies from 204 patients were subjected to histological examination and biopsies from 35 were subjected to immunohistochemical study of 8-hydroxy-2'deoxyguanosine, 8-oxoguanine-DNA-glycosylase, apurinic/apyrimidinic endonuclease and xeroderma pigmentosum A endonuclease.. Chronic proliferative atypical cystitis with multiple foci of dysplasia and carcinoma in situ were observed in 139 (89%) and in 91 (58%) of 156 group 1 patients from radio contaminated areas, respectively, as well as 10 small transitional cell carcinomas. Chronic cystitis with areas of dysplasia was detected in 9 of 48 patients (19%) in control group 2 from clean (without radio contamination) areas of Ukraine. Greatly elevated levels of 8-hydroxy-2'deoxyguanosine, 8-oxoguanine-DNA-glycosylase, apurinic/apyrimidinic endonuclease and xeroderma pigmentosum A were evident in the urothelium in group 1, accompanied by increased Cs in the urine.. These findings support the hypothesis that significant activation of DNA damage repair (base and nucleotide excision repair) is induced by the oxidative stress generated by long-term low doses of ionizing radiation. The levels of DNA oxidative adducts pointing to mutagenic and carcinogenic potential were in line with the histopathologically diagnosed urothelial lesions.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Aged, 80 and over; Carbon-Oxygen Lyases; Chronic Disease; Cystitis; Deoxyguanosine; DNA Damage; DNA Repair; DNA-(Apurinic or Apyrimidinic Site) Lyase; DNA-Formamidopyrimidine Glycosylase; Endonucleases; Female; Humans; Immunohistochemistry; Male; Middle Aged; N-Glycosyl Hydrolases; Neoplasms, Radiation-Induced; Oxidative Stress; Prostatic Hyperplasia; Radioactive Hazard Release; Ukraine; Urinary Bladder; Urinary Bladder Neoplasms; Urothelium

Abundant evidence has been gathered to suggest that mitochondrial DNA (mtDNA) sustains many more mutations and greater oxidative damage than does nuclear DNA in human tissues. Uremic patients are subject to a state of enhanced oxidative stress due to excess production of oxidants and a defective antioxidant defense system. This study was conducted to investigate mtDNA mutations and oxidative damage in skeletal muscle of patients with chronic uremia. Results showed that large-scale deletions between nucleotide position (np) 7,900 and 16,300 of mtDNA occurred at a high frequency in muscle of uremic patients. Among them, the 4,977-bp deletion (mtDNA(4977)) was the most frequent and most abundant large-scale mtDNA deletion in uremic skeletal muscle. The proportion of mtDNA(4977) was found to correlate positively with the level of 8-hydroxy 2'-deoxyguanosine (8-OHdG) in the total DNA of skeletal muscle (r = 0.62, p < 0.05). Using long-range PCR and DNA sequencing, we identified and characterized multiple deletions of mtDNA in skeletal muscle of 16 of 19 uremic patients examined. The 8,041-bp deletion, which occurred between np 8035 and 16,075, was flanked by a 5-bp direct repeat of 5'-CCCAT-3'. Some of the deletions were found in more than 1 patient. On the other hand, we found that the mean 8-OHdG/10(5 )dG ratio in the total cellular DNA of muscle of uremic patients was significantly higher than that of the controls (182.7 +/- 63.6 vs. 50.9 +/- 21.5, p = 0.05). In addition, the mean 8-OHdG/10(5 )dG ratio in muscle mtDNA of uremic patients was significantly higher than that in nuclear DNA (344.0 +/- 56.9 vs. 146.3 +/- 95.8, p = 0.001). Moreover, we found that the average content of lipid peroxides in mitochondrial membranes of skeletal muscle of uremic patients was significantly higher than that of age-matched healthy subjects (23.76 +/- 6.06 vs. 7.67 +/- 0.95 nmol/mg protein; p < 0.05). The average content of protein carbonyls in the mitochondrial membranes prepared from uremic skeletal muscles was significantly higher than that in normal controls (24.90 +/- 4.00 vs. 14.48 +/- 1.13 nmol/mg protein; p < 0.05). Taken together, these findings suggest that chronic uremia leads to mtDNA mutations together with enhanced oxidative damage to DNA, lipids, and proteins of mitochondria in skeletal muscle, which may contribute to the impairment of mitochondrial bioenergetic function and to skeletal myopathy commonly seen in uremic patients.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Case-Control Studies; Chronic Disease; Deoxyguanosine; DNA, Mitochondrial; Female; Humans; Lipid Metabolism; Male; Middle Aged; Muscle, Skeletal; Mutation; Oxidative Stress; Proteins; Reference Values; Reverse Transcriptase Polymerase Chain Reaction; Sequence Deletion; Uremia

Although Helicobacter pylori is a risk factor for gastric cancer, the role of the bacterium in the development of this malignancy is not defined precisely. Reactive oxygen species (ROS) could play an important role in carcinogenesis by inducing DNA damage. The aims of the present study were: 1) to assess the production of ROS and 8-hydroxy-2'-deoxyguanosine (8-OHdG), a sensitive marker of oxidative DNA injury, in gastric mucosa, according to H. pylori status and cytotoxic associated gene product A (CagA); 2) to determine the relationship between ROS generation and amount of 8-OHdG.. Gastric biopsy specimens were obtained from 60 consecutive patients. ROS generation was measured by luminol enhanced chemiluminescence. 8-OHdG detection was performed by an immunoperoxidase method, using a specific anti 8-OHdG monoclonal antibody.. 40/60 patients (67%) were H. pylori-positive. ROS generation was significantly higher in patients positive for H. pylori infection as compared to negative. 8-OHdG detection was performed in 30 patients in which CagA presence was also investigated. High expression of 8-OHdG was detected in 14/20 (70%) H. pylori-positive patients (13 CagA+ and 1 CagA-) and in 2/10 (20%) H. pylori-negative patients. A significant correlation was found between ROS production and 8-OHdG content.. H. pylori infection by a CagA+ strain is associated with the highest production of ROS to which a severe oxidative DNA damage corresponds. This sequence of events could support the hypothesis that the oxygen-free radicals-mediated damage due to H. pylori cytotoxic strains could be a driving force that leads from chronic gastritis to gastric carcinoma.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Antigens, Bacterial; Bacterial Proteins; Chronic Disease; Deoxyguanosine; DNA Damage; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Immunoenzyme Techniques; Luminescent Measurements; Male; Middle Aged; Reactive Oxygen Species; Stomach Neoplasms

There is an increasing body of evidence implicating reactive oxygen species in the pathogenesis of periodontal tissue destruction. 8-Hydroxy-deoxyguanosine (8-OHdG) is one of the most commonly used markers to evaluate oxidative damage in a number of disorders including chronic inflammatory diseases. The aim of the present study was to evaluate 8-OHdG levels in whole saliva of patients with periodontitis and to assess the changes after initial treatment.. Saliva samples were collected from 78 patients with untreated periodontitis and 17 healthy control subjects. Clinical parameters and levels of 8-OHdG were assessed first to establish a baseline and again after initial periodontal treatment from 15 patients. 8-OHdG levels were determined by enzyme-linked immunosorbent assay.. The mean value of 8-OHdG in the saliva of periodontally diseased subjects, 4.28 +/- 0.10 ng/ml, was significantly higher (P<0.01) than that of clinically healthy subjects (1.56 +/- 0.10 ng/ml). A significant decrease in salivary 8-OHdG was observed after therapy (P<0.01).. In the present study, we evaluated for the first time 8-OHdG levels in whole saliva of patients with periodontitis and assessed changes after initial periodontal treatment. Our study indicated that 8-OHdG levels in saliva appear to reflect the status of periodontal health.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Biomarkers; Chronic Disease; Dental Scaling; Deoxyguanosine; DNA Damage; Female; Follow-Up Studies; Gingival Hemorrhage; Humans; Male; Middle Aged; Oral Hygiene; Oxidative Stress; Periodontal Attachment Loss; Periodontal Pocket; Periodontitis; Reactive Oxygen Species; Root Planing; Saliva; Smoking; Statistics as Topic; Statistics, Nonparametric

Recent studies suggest that oxidative DNA damage induced during chronic inflammation may play a role in carcinogenesis in some organs. Although gallbladder carcinomas are frequently observed with a background of chronic cholecystitis, little is known about oxidative DNA damage in chronic cholecystitis. The aims of this study were to investigate the expression of 8-hydroxydeoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, in normal and chronically inflamed human gallbladder mucosa and compare its expression with clinicopathological findings.. 8-OHdG expression was immunohistochemically examined using a monoclonal antibody against 8-OHdG in human gallbladder specimens. In normal gallbladder (n=5), no 8-OHdG expression was observed. In contrast, nuclear expression of 8-OHdG was detected in 28 of 31cases (90.3%) in gallbladder epithelial cells with chronic cholecystitis. The positive cells were predominantly observed in the areas of active inflammation with prominent cell infiltration. Quantitative analysis revealed that the number of 8-OHdG+ cells (labelling index) significantly (rs=0.671, P < 0.05) correlated with the degree of the activity of mucosal inflammation, while gender, age, and the presence of gallstones did not influence the index.. Oxidative DNA damage is common in chronic cholecystitis, suggesting a possible link between chronic inflammation and gallbladder carcinogenesis.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Antibody Specificity; Biomarkers; Cholecystitis; Chronic Disease; Deoxyguanosine; DNA Damage; Female; Gallbladder; Humans; Immunohistochemistry; Male; Middle Aged

Although oxygen-derived free radicals are known to play a role in cell injury and DNA alterations, the role of active oxidants in chronic pancreatitis has not been fully elucidated. Using WBN/Kob rats, which spontaneously develop chronic pancreatitis-like lesions, we investigated whether xanthine oxidase (XOD)-derived oxygen radicals are involved in pancreatic tissue injury.. WBN/Kob rats were fed a control or a tungsten diet. The latter depletes XOD activity. Histologic al changes, glutathione (GSH) content and XOD and superoxide dismutase (SOD) activities were determined in pancreatic tissue. Pancreatic 8-hydroxy-deoxyguanosine (8-OH-dG) levels and lithostathine mRNA were also examined.. In WBN/Kob rats, parenchymal destruction and fibrosis developed at approximately 12 weeks of age and progressed with each month. The activity of XOD was significantly higher in the early period (8-12 weeks), whereas the levels of GSH and SOD decreased after 16 weeks. Levels of 8-OH-dG in WBN/Kob rats were significantly elevated at 16 weeks. Lithostathine mRNA levels started to increase at 8 weeks, but were suppressed at 16 weeks. The tungsten diet significantly attenuated the histological changes in WBN/Kob rats. The increase in pancreatic XOD activity and 8-OH-dG content in WBN/Kob rats was significantly inhibited by the tungsten diet and lithostathine mRNA levels remained high at 16 weeks.. These results suggest that oxygen radicals generated by XOD play an important role in oxidative DNA damage and the development of chronic pancreatic injury.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Amylases; Animals; Body Weight; Calcium-Binding Proteins; Chronic Disease; Deoxyguanosine; Glutathione; Lithostathine; Nerve Tissue Proteins; Pancreas; Pancreatitis; Procollagen-Proline Dioxygenase; Rats; Rats, Inbred Strains; Reactive Oxygen Species; RNA, Messenger; Superoxide Dismutase; Xanthine Oxidase

Helicobacter pylori infection causes gastric diseases, but the responsible mechanisms are not completely understood. They can involve DNA and tissue damage induced by reactive oxygen and nitrogen species. Our aim is to investigate the effects of bacterial eradication on oxidative stress by measuring changes of relevant markers.. Antral biopsies were obtained from 34 patients with chronic atrophic gastritis and peptic ulcer disease before and after bacterial eradication. The expression of inducible nitric oxide synthase (iNOS) and levels of nitrotyrosine (NTYR) and 8-hydroxy-2'-deoxyguanosine were assessed immunohistochemically as markers of nitric oxide (NO) production and of damage to proteins and DNA, respectively.. Before treatment, the percentages of patients with staining were: 56 for iNOS in inflammatory cells, 79 and 61 for NTYR and 8-hydroxy-2'-deoxyguanosine in foveolar cells, respectively, and 82 for 8-hydroxy-2'-deoxyguanosine in lymphoid follicles. NTYR staining was associated with the intensity of inflammation (p = 0.04) and gastritis activity (p = 0.07). The prevalence of 8-hydroxy-2'-deoxyguanosine tended to be associated with that of NTYR. After successful H. pylori eradication, the prevalence of iNOS and NTYR (in mild gastritis) staining decreased (p < 0.001 and p < 0.06, respectively). 8-Hydroxy-2'-deoxyguanosine staining disappeared in 24% of cases but appeared in 18% of previously negative cases despite eradication.. Targets of oxidative stress associated with H. pylori infection are inflammatory and deep foveolar cells and lymphoid follicles. This is the first report of 8-hydroxy-2'-deoxyguanosine localization in gastric mucosa. Oxidative stress is reduced by bacterial eradication in the first stages of mild gastritis. Moderate-severe gastritis may be a step that is reversible for iNOS, but partly irreversible for NTYR and 8-hydroxy-2'-deoxyguanosine.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Biomarkers; Chronic Disease; Deoxyguanosine; Female; Gastric Mucosa; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Immunohistochemistry; Male; Middle Aged; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Oxidative Stress; Peptic Ulcer; Tyrosine

Gastric carcinogenesis is a multifactorial, multistep process, in which chronic inflammation plays a major role.. In order to ascertain whether free radical mediated oxidative DNA damage is involved in such a process, concentrations of 8-hydroxydeoxyguanosine (8OHdG), a mutagenic/carcinogenic adduct, and thiobarbituric acid reactive substances (TBARS), as an indirect measure of free radical mediated damage, were determined in biopsy specimens from patients undergoing endoscopy.. Eighty eight patients were divided into histological subgroups as follows: 27 with chronic non-atrophic gastritis, 41 with atrophic gastritis, six with gastric cancer, and 14 unaffected controls.. Intestinal metaplasia, Helicobacter pylori infection, and disease activity were semiquantitatively scored. 8OHdG concentrations were assessed by HPLC with electrochemical detection, and TBARS concentrations were fluorimetrically assayed.. 8OHdG concentrations (mean number of adducts/10(5) dG residues) were significantly higher in chronic atrophic gastritis (p = 0.0009). Significantly higher concentrations were also detected in the presence of severe disease activity (p = 0.02), intestinal metaplasia (p = 0.035), and H pylori infection (p = 0.001). TBARS concentrations were also higher in atrophic gastritis, though not significantly so. In a multiple logistic regression analysis, 8OHdG concentrations correlated best with the presence and severity of H pylori infection (r = 0.53, p = 0.002).. Chronic gastritis is characterised by the accumulation of oxidative DNA damage with mutagenic and carcinogenic potential. H pylori infection is the major determinant for DNA adduct formation.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Aged, 80 and over; Analysis of Variance; Ascorbic Acid; Chronic Disease; Deoxyguanosine; DNA Damage; Female; Gastric Juice; Gastritis; Gastroscopy; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Reactive Oxygen Species; Regression Analysis; Stomach Neoplasms; Thiobarbituric Acid Reactive Substances