Higher 8-OHdG Levels Research Articles

Male infertility and viral infection: Interference role of the human herpesvirus types (3 – 6) with disturbances effects of some cytokines hypersecretion and seminal oxidative defense system in the infertility etiopathogenesis of some idiopathic infertile Iraqi patients

To study the role of potential relationship of chronic human herpes virus types (3 – 6) infection and their correlation with the up-regulation of some cytokines (IL-2, IL-10 and IFN gamma) and effect of (8-OHdG) and (TAOC) levels onto male infertility. A Case – control study with semen samples which were collected by masturbation during the routine semen analysis of a total ninety age-matched participants as; fertile males 35 (38.9%) with proven fertility as a normal semen quality and infertile males 55 (61.1%) with at least one year of infertility and poor semen quality. All semen biomarkers of Human herpes viruses (HHVs): Varicella zoster virus (VZV-IgG), Epstein-Barr virus (EBV-IgG), Cytomegalovirus (CMV-IgG), Human herpes virus type 6 (HHV6-IgG), Interlukin-2 (IL-2), Interlukin-10 (IL-10), Interferon-gamma (IFN-γ), 8-hydroxy-2'-deoxy guanosine (8-OHdG) and Total Antioxidant Capacity (TAOC) which were included in the study had been estimated by quantitative ELISA based method and the correlations with sperms parameters were evaluated. The main significant outcomes in this study of the infertile males group 55 (61.1%) were: high percentages of seminal IgG; N (%; Mean±SD) were detected of HHV6, 48 (53.3%;1.26± 0.51) then CMV, 39 (43.3%;1.51± 0.95) followed by EBV, 34 (37.8%; 2.20±1.47), and the highest abnormal cytokines levels were estimated in; 44 (48.9%; 112.62±38.64) and 40 (44.4%; 22.75±10.65) for IFN-γ and IL-10 respectively. Furthermore, High 8-OHdG level was detected in 47 (52.2%;7.29±2.15) and very low level of TAOC was detected in 16 (17.8%;19.34±12.17). Significant negative correlation between semen biomarkers and standard sperms parameters was found which were represented by: 45 (50.0%) of total sperms count less than (33 million ml), 52 (57.8%) of progressive motile sperms less than (31%). Finally, about 33 (24.4%) of abnormal sperm morphology was detected. Our results hypothesized that chronic asymptomatic viral infection with increasing of cytokines concentrations consequently disturbance the semen oxidative status, antioxidant defense systems that induce sperms DNA damage then might be collectively act as a co-factors on the etiology of the male infertility.

Measurement of urinary arsenic profiles and DNA hypomethylation in a case-control study of urothelial carcinoma.

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

Blood biomarkers of nicotine-induced toxicity in healthy males

BackgroundSmoking enhances oxidative stress by causing an oxidant/antioxidant imbalance in the body leading to deleterious effects on various tissues and organs. 8-hydroxy-2′-deoxyguanosine (8-OHdG) is a predominant form of free radical-induced oxidative lesions, and is widely used as a biomarker of oxidative stress.ObjectivesThis study aimed to estimate blood 8-OHdG level in active, passive and non-smokers and its relation with some lifestyle determinants as well as to assess smoking effects on oxidant/antioxidant status.Participants and methodsThe current work included 90 male participants who were classified into 3 groups; 20 non-smokers, 30 passive smokers, and 40 active smokers. Data were collected by answering a premade questionnaire. Peripheral venous blood samples were withdrawn then 8-OHdG, cotinine, superoxide dismutase (SOD), and total antioxidant capacity (TAC) levels were estimated in plasma using ELISA kits, while malondialdehyde (MDA) was estimated by colorimetry.ResultsThere were highly statistically significant higher levels of 8-OHdG, cotinine and MDA and lower levels of SOD and TAC in active smokers compared to both passive and non-smokers (p < 0.001) whereas, no statistically significant difference between passive and non-smokers was detected (p > 0.05). There were no significant differences between 8-OHdG level and smoking habits, age, exercise, tea and coffee consumption, and body mass index (BMI) among the 3 studied groups.ConclusionSmoking induces oxidative stress not only through the production of reactive oxygen radicals and increasing blood 8-OHdG levels but also through weakening of the antioxidant defense systems. Further studies are required to reach a consensus on the background level of 8-OHdG and understand which factors determine it and to further differentiate between passive and non-smokers.

Urinary levels of bisphenol A, F and S and markers of oxidative stress among healthy adult men: Variability and association analysis

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

Quantifying Cigarette Smoke Induced Oxidative DNA Damage of Wild Type &amp; XPC Knockdown Human Bronchial Cells Using Human 8-oxoguanine DNA Glycosylase 1

Background and Hypothesis: &#x0D; Chronic exposure to cigarette smoke (CS) induces DNA lesions and oxidative damage leading to the development of lung diseases such as emphysema and lung cancer. Xeroderma Pigmentosum group C (XPC) is a protein which repairs CS bulky DNA lesions and oxidative DNA damage, including 8-OHdG. We hypothesize that in vitro CS exposure will result in increased 8-OhdG and that XPC knockdown (KD) leads to higher levels of 8-OHdG. &#x0D; Experimental Methods: &#x0D; Briefly, immortalized normal human bronchial epithelial cells (Beas2B), were cultured and subsequently exposed to CS extract to induce DNA damage. Cells in agarose were then gently lysed, immersed in an alkaline buffer, incubated with hOGG1 enzyme, and analyzed for DNA damage using single cell electrophoresis (Comet Assay). Slides were stained and viewed by fluorescence microscopy. DNA damage is expressed as tail moment, measured by CometScore. Statistical analysis was performed using 2-way ANOVA (SigmaStat) with p-value &lt; 0.05 indicating statistical significance. &#x0D; Results and Conclusion: &#x0D; Both XPC KD and wild-type (WT) Beas2B cells treated with 2.5% CS measured higher levels of DNA damage than air control. The addition of hOGG1 lead to an increase in the tail moment in both AC and CS-exposed cells, indicating an increase in the oxidative DNA lesion, 8-OHdG. Finally, XPC KD exposed to 2.5% CS demonstrated an increase in DNA damage and in 8-OHdG compared to WT (p&lt;0.001). In conclusion, these results further support that CS leads to increased oxidative DNA damage and suggests a role for XPC in regulation and repair of the oxidative DNA lesion, 8-OHdG.

In vivo evaluation of the genotoxicity and oxidative damage in individuals exposed to 10% hydrogen peroxide whitening strips.

This study assessed the impact of 10% hydrogen peroxide whitening strip exposure on the genotoxicity and oxidative damage by means of the buccal micronucleus cytome assay by counting nuclear abnormalities (NAs) in buccal mucosa and attached gingiva cells and by analyzing in whole saliva the molecule 8-hydroxy-2'-deoxyguanosine (8-OHdG). The study was conducted on 113 subjects divided into two groups: group 1 or control (n = 53), non-whitening strip exposed, and group 2 (n = 60), whitening strip exposed (Crest® 3D Whitestrips® premium plus, 10% hydrogen peroxide). Oral epithelial cells and whole saliva samples were taken at the beginning and 30days later for group 1 and immediately before bleaching and 15 and 30days after the end of the bleaching for group 2. An increased frequency of NAs (p < 0.05) and higher levels of 8-OHdG (p < 0.05) were observed after bleaching exposure. Also, a positive correlation exists between oxidative stress produced by hydrogen peroxide and micronuclei was found. Individuals exposed to 10% hydrogen peroxide whitening strips exhibit NAs increased in oral epithelial cells and 8-OHdG in saliva, which is directed related to nuclear and oxidative DNA damage, respectively. Hydrogen peroxide is the active agent of tooth whitening and this compound induced DNA damage. Individuals exposed to whitening strips with 10% hydrogen peroxide exhibit increased genotoxic and oxidative damage. Therefore, self-application of bleaching agents should be handled carefully since it could be a risk to human health.

High serum uric acid is associated with oxidation of nucleosides in patients with type 2 diabetes

Uric acid presents different roles in an organism, since it can act as an antioxidant or a pro-oxidant molecule. High serum uric acid levels may cause damage to several structures, including nucleic acids and its components. Therefore, in this study the association between increased serum uric acid concentrations and oxidation of nucleosides was investigated by assessment of urinary 8-hydroxydeoxyguanosine (8-OHdG) in patients with type 2 diabetes (T2D) and in healthy individuals. Urinary 8-OHdG and biochemical parameters were assessed in 61 patients who were initially grouped into 2 groups based on the median serum uric acid levels (<5.3 mg/dL and ≥5.3 mg/dL). Urinary 8-OHdG was higher in patients with T2D and serum uric acid levels ≥5.3 mg/dL, when compared with the patients with serum uric acid levels <5.3 mg/dL; however, co-occurrence of high serum uric acid with high urinary 8-OHdG was not observed in healthy individuals. A significant positive correlation between 8-OHdG and uric acid (r = 0.40, P < 0.01) was observed in patients with T2D. High serum uric acid levels were associated with high urinary 8-OHdG levels in patients with T2D, and this association was independent of gender, hypertension, body mass index, and serum creatinine.

Lipid Peroxidation, Antioxidative Defense and Level of 8-Hydroxy-2-Deoxyguanosine in Cervical Cancer Patients

SummaryBackgroundOxidative stress has been associated with cervical cancer. Our aim was to examine lipid peroxidation and the extent of oxidative stress in women diagnosed with different stages of cervical cancer in order to evaluate its potential role in the evolution of cancer.MethodsWe measured the concentration of thiobarbituric acid reactive substances, activities of antioxidative enzymes and 8-hydroxy-2-deoxyguanosine in 153 subjects. Enzymatic activity as well as TBARS concentration were measured spectrophotometrically, while 8-OHdG was determined by gas chromatography-mass spectrometry. PPatients were categorized: group II H-SIL; group III FIGO Ia-Ib and group IV FIGO IIa-IV.ResultsOur results showed highly significant increase in the level of lipid peroxidation in group IV when com pared to the control group, group II and group III (p<0.001). Activity of superoxide dismutase was also significantly higher in group IV when compared to control group (p<0.01), group II (p<0.01) and group III (p<0.05). Activity of catalase was also significantly higher in group IV when compared to control group (p<0.005), group II (p<0.005) and group III (p<0.05). Activity of glutathione-S-transferase was also significantly higher in group IV when compared to control group (p<0.05), group II (p<0.05) and group III (p<0.05). Activities of glutathione peroxidase and glutathione reductase showed no significant differences among the groups. Level of 8-OHdG was significantly higher in group IV than in the other groups (p<0.01).ConclusionsIt can be concluded that oxidative stress is possibly involved in the pathogenesis of cervical cancer, demonstrated by increased lipid peroxidation and an altered antioxidant defense system and higher levels of 8-OHdG.

High serum levels of 8-OHdG are an independent predictor of post-stroke depression in Chinese stroke survivors.

PurposeAlthough previous studies have investigated oxidative stress biomarkers in association with depression in non-stroke subjects, the association between oxidative deoxyribonucleic acid damage and post-stroke depression (PSD) remains unelucidated.Patients and methodsTwo hundred forty-one first-ever ischemic stroke patients were consecutively recruited within the first 24 h of stroke onset and were followed up at 1 month. Serum 8-hydroxy-2′-deoxyguanosine (8-OHdG) and catalase (CAT) levels were measured within 24 h of admission using a commercially available enzyme-linked immunosorbent assay. The 17-item Hamilton Depression Scale was used to evaluate depressive symptoms. Diagnosis of PSD was made in line with the Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria for depression.ResultsSerum levels of 8-OHdG (P<0.001) and CAT (P=0.025) increased in depressed patients at admission. A positive correlation was found between the 8-OHdG and CAT levels in both the total stroke patients (r=0.320, P<0.001) and the depressed patients (r=0.300, P=0.012). The 8-OHdG levels were positively correlated with the 17-item Hamilton Depression Scale scores (r=0.129, P=0.046) in depressed patients. Multivariate analyses found that 8-OHdG levels ≥200.0 ng/L were independently associated with PSD (odds ratio, 7.477; 95% CI, 3.342–16.289, P<0.001) after adjusting for possible relevant confounders.ConclusionHigher serum 8-OHdG levels at admission were found to be correlated with PSD 1 month after stroke.

Elevated Serum 8-Hydroxy-2’-Deoxyguanosine, Nitrite, and Nitrate in Patients with Stage I Multiple Myeloma

Background: Reactive oxygen species are highly active intermediates, which lead to cellular damage during imbalance between oxidative stress/antioxidant towards oxidative stress. Free radicals have been proposed to have a crucial role in development and progression of human cancer. Objectives: The main aim of this study was to assess the changes in 8-hydroxy-deoxyguanosine (8-OHdG), nitrite (NO2-), and nitrate (NO3-) levels in patients with Stage I multiple myeloma (MM). Methods: The serum samples were obtained from 34 patients with stage I MM (22 males and 12 females at stage I) who were matched with healthy control group. Total serum of NO2- and NO3- levels, in addition to serum 8-OHdG levels, were assayed by using the commercial assay kit. Results: Compared with the healthy case group, the levels of serum NO2- and NO3- (2.54 ± 0.49 vs. 1.75 ± 0.52 µmol/L, P < 0.001 and 6.37 ± 0.94 vs. 2.63 ± 1.06 µmol/L, respectively, P < 0.001) were significantly increased in patients with MM. Higher levels of 8-OHdG in MM patients (157.08 ± 13.61 pg/mL) were observed and compared to the control group (61.48 ± 9.93 pg/mL) and indicated that 8-OHdG levels in patients with cancer were significantly increased than those of the control group (P < 0.001). Conclusions: Significantly increase in oxidative DNA damage and end-products of nitric oxide (NO) metabolism levels in patients with stage I MM suggest the possible involvement of oxidative stress in MM disease. These alterations can be associated with the imbalance in oxidant-antioxidant status in these patients and may contribute to carcinogenesis of MM by oxidative DNA damage.

High Serum Levels of Malondialdehyde and 8-OHdG are both Associated with Early Cognitive Impairment in Patients with Acute Ischaemic Stroke

Post-stroke cognitive impairment (PSCI) is an increasingly prevalent sequel after stroke that may associate with poor functional outcome and increased risk of recurrent stroke. We aimed to explore the relationship between oxidative stress biomarkers and the presence of PSCI. 193 first-ever acute ischaemic stroke patients were consecutively enrolled in the current study. The oxidative stress biomarkers malondialdehyde (MDA) and 8-hydroxydeoxyquanosine (8-OHdG) were measured within 24 h after admission. Cognition function was evaluated by the Mini-Mental State Examination (MMSE) at 1 month after stroke. Serum levels of 8-OHdG and MDA were both significantly higher in the PSCI (p < 0.001) compared with the non-PSCI group. Both the serum levels of both 8-OHdG and MDA were negatively correlated with the MMSE score. Receiver operating characteristic curve analysis was used to evaluate 8-OHdG and MDA as markers of a high risk of PSCI and produced area under curve values of 0.700 and 0.793. Adjusted logistic regression showed that serum 8-OHdG and MDA levels remained as independent markers of PSCI. High serum levels of malondialdehyde and 8-OHdG are associated with the presence of PSCI at 1 month after stroke.

The polymorphism XRCC1 Arg194Trp and 8-hydroxydeoxyguanosine increased susceptibility to arsenic-related renal cell carcinoma

This study was designed to explore the relationship between X-ray repair cross-complementing group 1 (XRCC1) gene polymorphisms and renal cell carcinoma (RCC) and to investigate whether individuals with an XRCC1 risk genotype, a high level of 8-OHdG or a high urinary total arsenic concentration have a modified odds ratio (OR) of RCC. We recruited 180 RCC patients and 360 age- and sex-matched controls from a hospital-based pool. Image-guided biopsy or surgical resection of renal tumors was performed on RCC patients for pathological verification. Genomic DNA was used to examine the genotype of XRCC1(Arg399Gln), XRCC1(Arg194Trp), XRCC3(Thr241Met) and XPD(Lys751Gln) by PCR-RFLP. Liquid chromatography with tandem mass spectrometry was used to determine urinary 8-OHdG levels. A HPLC-HG-AAS was used to determine the concentrations of urinary arsenic species. Participants with the genotype XRCC1(Arg194Trp) Arg/Trp+Trp/Trp had a significantly higher OR of RCC than those with the Arg/Arg genotype; the OR and 95% confidence interval was 0.66 (0.45–0.97) after multivariate adjustment. The OR of RCC for the combined effect of high urinary 8-OHdG levels and high urinary total arsenic concentration in individuals with a XRCC1(Arg194Trp) Arg/Trp+Trp/Trp genotype was higher than in patients with an Arg/Arg genotype, which was evident in a dose response manner. In conclusion, this is the first study to show that the XRCC1 Arg194 allele is a predicting factor for RCC. The more risk factors (high urinary 8-OHdG levels, high urinary total arsenic concentrations, and XRCC1 Arg194 allele) that were present, the higher the OR of RCC.

Environmental conditions can modulate the links among oxidative stress, age, and longevity

Understanding the links between environmental conditions and longevity remains a major focus in biological research. We examined within-individual changes between early- and mid-adulthood in the circulating levels of four oxidative stress markers linked to ageing, using zebra finches (Taeniopygia guttata): a DNA damage product (8-hydroxy-2′-deoxyguanosine; 8-OHdG), protein carbonyls (PC), non-enzymatic antioxidant capacity (OXY), and superoxide dismutase activity (SOD). We further examined whether such within-individual changes differed among birds living under control (ad lib food) or more challenging environmental conditions (unpredictable food availability), having previously found that the latter increased corticosterone levels when food was absent but improved survival over a three year period. Our key findings were: (i) 8-OHdG and PC increased with age in both environments, with a higher increase in 8-OHdG in the challenging environment; (ii) SOD increased with age in the controls but not in the challenged birds, while the opposite was true for OXY; (iii) control birds with high levels of 8-OHdG died at a younger age, but this was not the case in challenged birds. Our data clearly show that while exposure to the potentially damaging effects of oxidative stress increases with age, environmental conditions can modulate the pace of this age–related change.

CHD4 Has Oncogenic Functions in Initiating and Maintaining Epigenetic Suppression of Multiple Tumor Suppressor Genes

An oncogenic role for CHD4, a NuRD component, is defined for initiating and supporting tumor suppressor gene (TSG) silencing in human colorectal cancer. CHD4 recruits repressive chromatin proteins to sites of DNA damage repair, including DNA methyltransferases where it imposes de novo DNA methylation. At TSGs, CHD4 retention helps maintain DNA hypermethylation-associated transcriptional silencing. CHD4 is recruited by the excision repair protein OGG1 for oxidative damage to interact with the damage-induced base 8-hydroxydeoxyguanosine (8-OHdG), while ZMYND8 recruits it to double-strand breaks. CHD4 knockdown activates silenced TSGs, revealing their role for blunting colorectal cancer cell proliferation, invasion, and metastases. High CHD4 and 8-OHdG levels plus low expression of TSGs strongly correlates with early disease recurrence and decreased overall survival.

Effects of smoking on concentration of urinary 8-hydroxydeoxyguanosine in coke oven workers

Objective: To explore the influence of smoking and polycyclic aromatic hydrocarbons (PAHs) on urinary 8-hydroxydeoxyguanosine (8-OHdG) in coke oven workers and investigate their dose-dependent relationships. Methods: A total of 436 workers exposed to coke oven emissions (COEs) and 132 controls were recruited in this study. Questionnaires were completed in a personal interview. Then their urine samples were also collected and the concentrations of urinary four OH-PAHs and 8-OHdG were determined by high performance liquid chromatography (HPLC) which was used to evaluate the levels of occupational PAHs internal exposure among workers and the DNA damage. Results: The differences of concentrations of urinary 2-NAP (2-hydroxynathalene) , 2-FLU (2-hydroxyfluorene) , 9-PHE (9-hydroxyphenanthrene) , 1-OHP (1-hydroxypyrene) between exposure group and control group were statistically significant (P<0.05) . In exposure group and control group, the level of 8-OHdG in heavy smoking workers were significantly higher than that in other groups (P<0.05) . Multivariate logistic regression analysis revealed high levels of urinary 8-OHdG were associated with a significantly increased risk of having higher urinary1-hydroxypyrene levels[OR=1.43 (95%CI: 1.06-1.94) , P<0.01] and heavy smoking [OR=1.44 (95%CI: 1.08-1.91) , P<0.01], respectively. Trend test showed that linear dose response relationship between smoking, 1-OHP in urine and higher concentrations of 8-OHdG (P<0.05) . Smoking could significant modify the effects of urinary 1-hydroxypyrene, while co-exposure to both heavy smoking and high urinary 1-hydroxypyrene levels[OR=5.64 (95%CI: 2.15-14.80) , P<0.05]. Conclusion: Urinary 1-hydroxypyrene is a useful biomarker for evaluating total PAHs exposure, coke oven workers with heavy smoking present more serious DNA oxditive damage.

Cancer risk associated single nucleotide polymorphisms of mitochondrial D-loop and 8-hydroxy-2'-deoxyguanosine levels in gastric cancer

ABSTRACTThe accumulation of mutations and single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) is related to gastric carcinogenesis. To evaluate the potential relationships between DNA damage and D-loop SNPs, we measured the 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in the gastric cancer tissue by immmunostaining. Our data showed that the gastric cancer susceptibility SNP of 16519C was associated with higher 8-OHdG levels. Taken together, the cancer-risk associated D-loop SNPs might initiate carcinogenesis through increasing oxidative damage.

Use of anabolic androgenic steroids produces greater oxidative stress responses to resistance exercise in strength-trained men.

The aim of this study was to determine the effect of anabolic androgenic steroids (AAS) use on oxidative stress responses to a single session of resistance exercise in strength-trained men. Twenty-three strength trained men, with 11 self-reporting regular AAS use and 12 self-reporting never taking AAS (NAAS) volunteered to participate in this study. Blood draws were obtained pre and post resistance exercise in order to evaluate changes in oxidative stress biomarkers levels (i.e., 8-hydroxy-2-deoxyguanosine [8-OHdG], malondialdehyde [MDA], and nitric oxide [NO]), antioxidant defense systems (i.e., glutathione peroxidase [GPx] and catalase [CAT]), and glucose (GLU) levels. The AAS users had higher level of 8-OHdG (77.3±17 vs. 57.7±18.2ng/mg), MDA (85.6±17.8 vs. 52.3±15.1ng/mL), and GPx (9.1±2.3 vs. 7.1±1.3mu/mL) compared to NAAS at pre exercise (p<0.05). Both the experimental groups showed increases in 8-OHdG (p=0.001), MDA (p=0.001), GPx (p=0.001), NO (p=0.04), CAT (p=0.02) and GLU (p=0.001) concentrations after resistance exercise, and the AAS group indicated significant differences in 8-OHdG (p=0.02) and MDA (p=0.05) concentrations compared with NAAS users at post exercise. In conclusion, use of AAS is associated with alterations in immune function resulting in oxidative stress, and cell damage; however, high-intensity resistance exercise could increase greater oxidative stress biomarkers in strength-trained men.

Oxidative Stress Is Associated with Poor Prognosis in Patients with Follicular Lymphoma

[Introduction] Follicular lymphoma (FL) is an indolent non-Hodgkinfs lymphoma (NHL), with a highly variable clinical course that can range from indolent to rapidly progressive disease, including the transformation to aggressive NHL. Oxidative stress caused by the increased production of reactive oxygen species (ROS) or decreased efficacy of the antioxidant system is implicated in the pathogenesis of various disease entities, such as atherosclerosis, cardiovascular disease, renal failure, malignant tumors, and autoimmune diseases. Recent observations suggested that oxidative stress is closely related to all aspects of cancer. Oxidative stress markers are prognostically important in various cancers including diffuse large B-cell lymphoma (DLBCL). However, the prognostic role of oxidative stress in FL is still unknown. The objective of this study is to evaluate the role of oxidative stress in patients with FL.[Methods] 8-hydroxy-2-deoxyguanosine (8-OHdG), which originates from damaged DNA repaired by non-specific endonucleases and specific glycosylates and is eliminated into urine, is widely used as a sensitive biomarker of oxidative stress. Urinary 8-OHdG levels have been reported to be elevated in patients with various malignancies. In the present study, urinary 8-OHdG levels were prospectively examined in 30 patients with FL by using a novel automatic oxidative stress analyzer, ICR-001. We also evaluated serum d-ROMs (the derivatives of Reactive Oxygen Metabolites) levels by using the Free Radical Analytical System 4 (FRAS 4, Wismerll Co. Ltd., Tokyo, Japan). The d-ROMs test has been successfully used to evaluate oxidative stress in a very large number of studies on humans and animals. The d-ROMs test essentially determines the concentration of hydroperoxides in the blood, which are substances that belong to a broad class of reactive oxygen metabolites. The d-ROMs concentration is expressed in Carratelli Units (1 CARR U = 0.08mg hydrogen peroxide/dl). The study protocol and sampling were approved by the Institutional Review Board of Yokohama Municipal Citizen's Hospital, and it was carried out in accordance with the Declaration of Helsinki.[Results] Median age at diagnosis was 70 years (range, 43-84 years) and 53% were male. According to the WHO pathological grading, grade 1 FL was observed in 16 patients (53%), grade 2 FL in 8 patients (27%), and grade 3 FL in 6 patients (20%). FLIPI scores were 0 to 1 in 27%, 2 in 27%, and 3 to 5 in 46%.The urinary 8-OHdG levels in patients with FL (N=30) were elevated compared with normal controls (N=20) (19.7+/-10.3 vs. 13.7+/-3.4 ng/mg/Cr, P=0.01). In 30 FL patients, patients with high urinary 8-OHdG levels (over 23.9 ng/mg/Cr) had significantly shorter overall survival (OS) than those with low urinary 8-OHdG levels (under 23.9 ng/mg/Cr) (3-year OS, 33.3% versus 90.5%, respectively; P<0.001) (Figure. 1). The serum d-ROMs levels in patients with FL were significantly elevated compared with normal controls (543.9+/-199.4 vs. 281.1+/-25.9 CARR U, P<0.001). Patients with high serum d-ROMs levels (over 519 CARR U) had significantly shorter overall survival (OS) than those with low serum d-ROMs levels (under 519 CARR U) (3-year OS, 41.7% versus 94.4%, respectively; P<0.001) (Figure. 2). In univariate analysis, high 8-OHdG levels, high d-ROMs levels, high PS, high LDH levels, high tumor burden (GELF criteria), high beta-2 microglobulin levels, and high FLIPI score were associated with poor OS in patients with FL. In multivariate analysis, parameters having independent adverse significance for OS were: high serum d-ROMs levels (over 519 CARR U) (p=0.01, HR 15.68), high LDH levels (p=0.02, HR 12.25).[Conclusion] In the present study we demonstrated that elevated urinary 8-OHdG levels and serum d-ROMs levels are associated with poor prognosis in patients with FL. In particular, our data proved that a high serum d-ROMs level is an independent prognostic factor for survival in patients with FL. These results suggest that oxidative stress may have an important role in FL and also may be a useful prognostic biomarker. Since our results are based on a small-sized analysis, further large prospective studies are warranted to verify this conclusion. [Display omitted] [Display omitted] DisclosuresNakazato:Mundipharma KK: Research Funding.

Associations of PARP-1 variant rs1136410 with PARP activities, oxidative DNA damage, and the risk of age-related cataract in a Chinese Han population: A two-stage case-control analysis

ObjectiveTo investigate whether a single nucleotide polymorphism (SNP) rs1136410 in the poly (ADP-ribose) polymerase-1 (PARP-1) gene was associated with PARP activities, 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels, and the risk of age-related cataract (ARC) in a Chinese Han population. MethodsIn this two-stage case-control study with a total of 1010 ARC patients and 1045 controls, SNP rs1136410 was genotyped by high-resolution melting analyses (HRM). PARP activities and 8-OHdG levels in peripheral blood mononuclear cells (PBMCs) were determined by ELISA kits. ResultsIn discovery, replication, and their merged sets, the variant genotypes (AG+GG) of SNP rs1136410 were significantly associated with an increased risk of ARC under a dominant model (Adjusted odds ratio (OR)=1.42, Padj=0.001 for the merged set). This association was further identified in subtype analyses for cortical ARC (Adjusted OR=1.69, Padj<0.001). In subgroup analyses, we identified a significant interaction between SNP rs1136410 and smoking habit in increasing ARC risk (Pinter=0.019). Moreover, ARC patients had lower activities of PARP and higher levels of 8-OHdG than controls. There were significant correlations of SNP rs1136410 with decreased PARP activities and increased 8-OHdG levels in controls and patients with cortical ARC. ConclusionsThis study suggests that SNP rs1136410 may confer susceptibility to ARC by affecting PARP activities and oxidative DNA damage.

An Assessment of Oxidative Damage and Non-Enzymatic Antioxidants Status Alteration in Relation to Disease Progression in Breast Diseases.

The present study was aimed to evaluate the levels of oxidative stress markers in breast diseases by measuring the 8-hydroxy-2-deoxyguanosine (8-OHdG), vitamin A, vitamin C, vitamin E, and total antioxidant status (TAS) alterations in relation to cell proliferation activity and disease progression. Significant increases in the level of the oxidative damage marker 8-OHdG and cell proliferation activity were observed in breast carcinoma patients in comparison to benign and normal controls, which were accompanied by a significant decrease in non-enzymatic antioxidants and TAS concentrations (p < 0.05). 8-OHdG and cell proliferation levels were negatively correlated with non-enzymatic antioxidants, namely, vitamin A, vitamin C, and vitamin E levels and total antioxidant activity. Altered levels of biomarkers of oxidative stress and cell proliferation activity among the malignant, the benign, and the controls suggest a correlation of increased oxidative stress and cell proliferation activity in the progression of disease in breast carcinoma patients. In conclusion, our results showed that the characterized biomarkers (i.e., low levels of vitamin A, C and D, and the TAS status; and high levels of 8-OHdG) could be used as a suitable method for detecting subjects with malignant and benign breast diseases.