Urinary 8-OHdG Levels Research Articles

Urinary 8-hydroxydeoxyguanosine as a marker of oxidative stress induced genetic toxicity in oral cancer patients.

Recently, non-communicable diseases have snatched the lead from infectious diseases in causing mortality. Of these, oral cancer accounts for a significant proportion of deaths. Every year in India significant percentage of newly diagnosed malignancy is oral cancer attributed to various reasons. The aim of this study was to assess the extent of oxidative stress and its effect on modification of DNA by urinary nucleoside 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in oral cancer subjects. To see the relationship between the nucleoside 8-OHdG and antioxidant capacity ferric reducing ability plasma (FRAP) in oral cancer subjects. Case-control study included three groups with 60 volunteers, who were divided into 30 controls, and equal number of clinically diagnosed oral cancer male patients: (Subdivided into newly diagnosed [n = 15] and 1-year treatment follow-up oral cancer subjects [n = 15]). A random urine sample was used for analysis of 8-OHdG concentration. Serum triglycerides, lipid peroxidation, protein thiols, and FRAP assay were performed by spectrophotometric technique. Student's t-test and one-way analysis of variance were performed for group comparison and Pearson's correlation analysis were used. A P < 0.05 was considered the optimum level of significance. The urinary 8-OHdG and serum malondialdehyde levels were significantly elevated in newly diagnosed oral cancer subjects in their 1-year treatment compared to the control group (P < 0.05). A significant correlation was observed between urinary 8-OHdG and FRAP in both groups of oral cancer subjects. Urinary 8-OHdG can be a useful diagnostic marker of oxidative DNA damage in oral cancer subjects.

Tumor Necrosis Factor-Alpha and 8-Hydroxy-2'-Deoxyguanosine are Associated with Elevated Urinary Angiopoietin-2 Level in Type 2 Diabetic Patients with Albuminuria

Background/Aims: We previously showed that urine and serum Angiopoietin-2 (Ang-2) levels increased significantly with the degree of albuminuria in diabetes patients, but the reasons remain unclear. Consequently we aimed to determine whether there was an association between Ang-2, inflammatory cytokines (TNF-α and IL-18) and reactive oxygen species (8-OHdG and SOD) in type 2 diabetes patients with albuminuria. Methods: This retrospective study evaluated 113 patients with type 2 diabetes and normoalbuminuria, microalbuminuria, or macroalbuminuria and 30 healthy controls. Serum and urine TNF-α, IL-18 and 8-OHdG levels were measured by ELISA. Superoxide dismutase (SOD) activity was determined by spectrophotometry. Results: Serum and urine TNF-α, IL-18 and 8-OHdG levels increased significantly with the degree of albuminuria, and were positively correlated with increased Ang-2. In contrast, SOD activity decreased with the degree of albuminuria and was negatively correlated with Ang-2. Multivariable linear regression analysis revealed that serum Ang-2 level was independently associated with serum levels of TNF-α (P<0.001), 8-OHdG (P=0.001), and IL-18 (P=0.003). Urinary Ang-2 level was independently associated with urinary TNF-α (P<0.001) and 8-OHdG (P=0.004) levels. Conclusion: TNF-α and 8-OHdG are associated with elevated urinary Angiopoietin-2 levels in type 2 diabetic patients with albuminuria.

Urinary DNA lesions as a biomarker for assessing male reproductive health

The study aimed to examine whether urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) could serve as a biomarker for assessing sperm DNA integrity. Urine and semen samples were collected from 124 coke-oven workers, who had chronically been exposed to polycyclic aromatic hydrocarbons (PAHs), from a steel plant in Kaohsiung, Taiwan. The coke-oven workers were divided into two subgroups: topside-oven workers and side-oven workers. Sperm DNA integrity was assessed in terms of DNA fragmentation and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo). Urine samples were used to detect 1-hydroxypyrene (1-OHP) and urinary 8-OHdG, which served to assess exposure to PAHs and the whole body oxidative stress, respectively. Urinary 1-OHP concentrations were significantly higher in the topside-oven workers than the side-oven workers ( p = 0.02). Sperm 8-oxodGuo concentrations were correlated with percentages of sperm fragmentation ( p = 0.044), but urinary 8-OHdG levels failed to correlate with sperm 8-oxodGuo levels and with percentages of fragmentation. In conclusion, exposure to PAHs was linked to increased oxidative stress on sperm. However, urinary 8-OHdG may not be a suitable biomarker for examining sperm DNA damage associated with oxidative stress.

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

[Introduction] 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. However, the prognostic role of oxidative stress in hematologic malignancies (HM) is still unknown. The objective of this study is to evaluate the role of oxidative stress in patients with HM.[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 examined in 196 patients with HM (112 malignant lymphoma, 34 multiple myeloma, 28 myelodysplastic syndrome, 15 acute myeloid leukemia, 3 acute lymphoblastic leukemia, 4 chronic myeloid leukemia) by using a novel automatic oxidative stress analyzer, ICR-001. The study protocol and sampling were approved by the Institutional Review Board of Yokohama Municipal Citizen’s Hospital.[Results] The urinary 8-OHdG levels in patients with HM were elevated compared with normal controls (23.2+/-18.3 vs. 13.7+/-3.4ng/mg/Cr, P=0.02). In particular, urinary 8-OHdG levels were significantly elevated in patients with malignant lymphoma (25.9+/-31.4ng/mg/Cr, P=0.02). In 112 lymphoma patients, patients with high urinary 8-OHdG levels (over 25.0ng/mg/Cr) had significantly shorter overall survival (OS) than those with low urinary 8-OHdG levels (under 25.0ng/mg/Cr) (2-year OS, 44.0% versus 83.4%, respectively; P<0.001) (Figure. 1). Among lymphoma patients, urinary 8-OHdG levels were significantly higher in patients with diffuse large B-cell lymphoma (DLBCL) (31.04+/-36.54ng/mg/Cr, P=0.01). In 55 DLBCL patients, high urinary 8-OHdG levels were also associated with shorter OS (2-year OS, 31.1% versus 88.9%, respectively; P<0.001) (Figure. 2). In univariate analysis, a high 8-OHdG level, high PS, a high LDH level, advanced stage, a high sIL2R level, and R-IPI poor risk were associated with poor OS in patients with DLBCL. In multivariate analysis, parameters having independent adverse significance for OS were: a high urinary 8-OHdG level (over 25.0ng/mg/Cr) (p=0.01, HR 4.97), high PS (2-4) (p=0.01, HR 6.61).[Conclusion] In the present study we demonstrated that many patients with HM have elevated urinary 8-OHdG levels, and these elevated levels are associated with a poor prognosis in patients with ML. In particular, our data proved that a high urinary 8-OHdG level is an independent prognostic factor for survival in patients with DLBCL. These results suggest that oxidative stress may have an important role in ML 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] DisclosuresNo relevant conflicts of interest to declare.

Inhibitory effects of astaxanthin on azoxymethane-induced colonic preneoplastic lesions in C57/BL/KsJ-db/db mice.

BackgroundObesity and related metabolic abnormalities, including excess oxidative stress and chronic inflammation, are associated with colorectal carcinogenesis. Astaxanthin, a xanthophyll carotenoid found in aquatic animals, is known to possess antioxidant, anti-inflammatory, and antineoplastic properties. The present study examined the effects of astaxanthin on the development of azoxymethane (AOM)-induced colonic premalignant lesions in C57BL/KsJ-db/db (db/db) obese mice.MethodMale db/db mice were administered 4 weekly subcutaneous injections of AOM (15 mg/kg body weight) from 5 weeks of age and subsequently, from 1 week after the last injection of AOM, were fed a diet containing 200 ppm astaxanthin throughout the experiment (8 weeks).ResultThe development of colonic premalignant lesions, i.e., aberrant crypt foci and β-catenin accumulated crypts, was significantly inhibited in mice treated with astaxanthin than in mice fed the basal diet. Astaxanthin administration markedly reduced urinary levels of 8-OHdG and serum levels of d-ROMs, which are oxidative stress markers, while increasing the expression of mRNA for the antioxidant enzymes GPx1, SOD1, and CAT in the colonic mucosa of AOM-treated db/db mice. The expression levels of IL-1β, IL-6, F4/80, CCL2, and CXCL2 mRNA in the colonic mucosa of AOM-treated mice were significantly decreased by astaxanthin. Dietary feeding with astaxanthin also resulted in a reduction in the numbers of NF-κB- and PCNA-positive cells that were increased by AOM exposure, in the colonic epithelium.ConclusionThese findings suggest that astaxanthin inhibits the development of colonic premalignant lesions in an obesity-related colorectal carcinogenesis model by reducing oxidative stress, attenuating chronic inflammation, and inhibiting NF-κB activation and cell proliferation in the colonic mucosa. Astaxanthin, therefore, may be a potential candidate as a chemoprevention agent against colorectal carcinogenesis in obese individuals.

Abstract 3839: Oxidative damage in predicting early adverse skin reactions from adjuvant radiotherapy in a tri-racial/ethnic breast cancer population

Abstract Adjuvant radiotherapy (RT) following breast conservation surgery has significantly improved survival. However, may patients develop adverse skin reactions, pain, breast edema and poor cosmetic results that impact quality of life. Inter-individual variability in the development of RT-induced adverse reactions in normal tissue is well-documented for both acute and late effects. Therefore, we evaluated the first 161 patients in an ongoing prospective study of conservatively managed breast cancer patients using the NCI CTCAE v3.0 criteria. We recorded patient characteristics, smoking history, body mass index (BMI), and treatments. We pilot tested urinary 8-hydroxydeoxyguanosine (8-OHdG) as an oxidative damage marker in predicting RT-induced skin toxicity. Women younger than 50 years of age had a significantly (p=0.016) higher post-RT skin toxicity (grade 2); higher proportion of African Americans have grade 3 skin (p=0.008) compared to other races; and obesity (BMI&amp;gt;30) was associated with worse skin toxicity. In multivariate analysis, women with a higher pre-RT 8-OHdG had a significantly higher risk of worse skin toxicity at week 3 (OR=11.77; 95C%CI=1.21-114.45; p=0.034). Obesity (BMI&amp;gt;30) was associated with worse skin toxicity at the end of RT (OR=2.27; 95C%CI=1.14-4.50; p=0.019). This is the first study evaluating oxidative damage in RT-induced skin toxicity. We reported significant racial/ethnic differences in urinary 8-OHdG levels and a significant association between pre-RT 8-OHdG and worse skin toxicity at week 3. If confirmed in our larger ongoing study of 1,255 patients, our study will lead to effective treatment strategies and improve quality of life of breast cancer patients undergoing RT. Citation Format: Omar L. Nelson, Cristiane Takita, Jean Wright, Eunkyung Lee, Jennifer J. Hu. Oxidative damage in predicting early adverse skin reactions from adjuvant radiotherapy in a tri-racial/ethnic breast cancer population. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3839. doi:10.1158/1538-7445.AM2014-3839

Effects of supplemental oxygen on urinary 8-hydroxy-2’-deoxyguanosine levels in extremely low birth weight infants

As the effects of supplementary oxygen on urinary excretion of 8-hydroxy-2’-deoxyguanosine (8-OHdG) are poorly understood, urinary 8-OHdG levels (ng/mg creatinine) were determined longitudinally on the postnatal day (PND) 1, 3, and 30 in 16 neonates with birth weight < 1000 g. No supplementary oxygen was required in 9 neonates during the first 24 h of life. Urinary 8-OHdG level on PND 1 was inversely correlated with birth weight in these 9 neonates (P = 0.0323) and was higher in four with birth weight < 750 g than five with birth weight > 750 g (41.0 ± 6.9 vs. 5.6 ± 2.7, respectively, P = 0.0200). Median urinary 8-OHdG on PND 1 of these 9 neonates was significantly lower than that of 7 neonates with oxygen (9.3 vs. 60.2, respectively), although there were no significant differences in clinical background, such as birth weight, between the two groups. Five of the 9 did not require supplemental oxygen at all during the first 30 days of life. Median urinary 8-OHdG levels were consistently significantly lower in the 5 neonates than in 11 neonates with oxygen transiently or persistently (9.3 vs. 54.6, 19.1 vs. 61.4, and 28.3 vs. 145 on PND 1, 3, and 30, respectively), although there were no differences in clinical background, such as birth weight, between the two groups. Urinary 8-OHdG on PND 30 was significantly positively correlated with supplemental oxygen dose on PND 30 (P < 0.0001), but not with birth weight in the 16 neonates. These results suggest that higher supplemental oxygen tension caused higher urinary 8-OHdG in this population.

Changes in urinary 8-hydroxydeoxyguanosine levels during heptathlon race in professional female athletes.

Acute strenuous exercise can induce a state of oxidative stress affecting the involved muscles. Heptathlon is a multi-event exercise of two days duration and can be considered an acute, intensive endurance exercise. The purpose of this study is to compare the oxidative stress response to heptathlon events day by day and to determine the impact of this type of exercise on oxidative stress biomarkers.The study subjects included eight heptathlon athletes who participated in the National First Class Republic competition in Egypt (October 19–21, 2011). Blood samples were collected at rest after exercise for two successive days and analyzed for malondialdehyde (MDA). Morning urine samples were collected one hour after exercise for each day and were analyzed for 8-hydroxydeoxyguanosine (8-OHdG). Results revealed a significant increase (p<0.05) in both plasma MDA and urine 8-OHdG levels after exercise regardless of the day. We concluded that exercise generates higher MDA levels compared to DNA strand breaks and oxidative DNA damage in athletes with antioxidant supplementation.

Combined Treatment of Tacrolimus and Everolimus Increases Target Organ Injury Via Increasing P-Glycoprotein and Cytochrome P450.

It is not clear the influence of combined treatment of tacrolimus (TAC) and everolimus (EVR). In this study, we investigated; first, whether combined treatment of EVR and TAC affects organ dysfunction and oxidative stress; second, whether these combined treatment affect each drug level at the blood and target organ tissues and third, the mechanisms of drug-drug interaction by assessing P-glycoprotein and cytochrome P450.Rat was orally administrated with TAC (6 mg/kg/day) and EVR (1 or 2 mg/kg/day) for 4 weeks. The effect of EVR on TAC-induced organ injury was also compared with that of EVR and TAC treatment alone. Oxidative stress was measured with 8-hydroxy-2'-deoxyguanosin (8-OHdG) in serum and 24 hour urine. To confirm the drug interaction between and EVR or TAC, concentration of each drug was evaluated in the whole blood and tissue (kidney, pancreas and liver) using LC/MS/MS. The mechanism of drug interaction was evaluated by the expression of P-glycoprotein and cytochrome P450 in target organ tissues using immunoblot analysis. TAC or EVR treatment alone did not caused overt renal, pancreatic islet, and liver injury, but addition of EVR significantly increased the TAC-induced injury, as demonstrated by aggravated nephrotoxicity, pancreatic islet and liver dysfunction. In blood and target organs e.g. liver, kidney and pancreas, surprising higher TAC or EVR level were detected in combined group compared with single treated groups. And there was good correlation between two drugs in blood and target organs. The serum and urinary 8-OHdG level were significantly increased in the TAC and EVR combined treated group compared with the TAC or EVR alone group, and were well correlated with drug levels in the blood and tissues. TAC or EVR alone treated groups showed higher expression of P-glycoprotein than control, and combined treatment was further increased its expression compared to the TAC or EVR alone treatment groups. Consistently, cytochrome P450 also showed much higher level in combined group compared to the single treated groups. We conclude that addition of EVR aggravates TAC-induced organ injury and pharmacologic drug-drug interaction. The reason for drug interaction between two drugs is related to the mutual competitive interactions targeting P-glycoprotein and cytochrome P450.

The Possible Ameliorative Effect of Curcumin on Atrazine-Induced Oxidative Stress, DNA Damage, Mitochondrial Dysfunction, and Apoptosis in the Kidney of Adult Male Albino Rats

Introduction: Atrazine (ATR), a worldwide triazine herbicide, induces oxidative stress and DNA damage. It was found that oxidative stress is closely linked to apoptosis. Curcumin has strong antioxidant, antimicrobial, anticancer and anti-inflammatory actions. Aim of the study: The aim of this study was to assess the possible ameliorative effect of curcumin on ATR- induced oxidative stress, oxidative DNA damage, mitochondrial dysfunction, and apoptosis in the kidney of adult male albino rats. Material and methods: The current study was conducted on 40 adult male albino rats. Rats were divided into four equal groups. The first group was control. Group II was treated with curcumin (100mg/kg/day). Group III was treated with ATR (400mg/kg/day). Group IV was treated with both ATR (400mg/kg/day) and curcumin (100mg/kg/day). All were given orally for 21days. Body and kidney weights, blood urea and creatinine as well as 24 hours urinary protein levels were measured. Levels of malondialdehyde (MDA), reduced glutathione (GSH), and 8-Hydroxy-2′-deoxyguanosine (8- OHdG) as well as activities of catalase (CAT), heme oxygenase-1 (HO-1) and complex-1 were assessed. Histopathological and immunohistochemical examination of renal tissue were carried out. Results: ATR treated group was significantly decreased in body and kidney weights, GSH level and HO-1 as well as complex 1 activities while there was significant increase in blood urea, creatinine, 24 hours urinary protein, MDA and 8-OHdG levels as well as CAT activity. Renal cloudy swelling was observed in H&E sections. Caspase 3 immunohistochemistry revealed high rate of apoptosis. Curcumin administration along with ATR significantly improved these observations. Conclusion: It was concluded that administration of curcumin along with ATR ameliorated oxidative stress, DNA damage, mitochondrial dysfunction and apoptosis induced by ATR. Recommendations: The current study recommend further studies to clarify issues related to human exposure to ATR and the ameliorative effect of curcumin in Egypt and elsewhere around the world.

Antiaging therapy: a novel target for antilipolytic drugs.

Aging has been defined as a gradually decreasing ability to maintain homeostasis and increasing risk to die. Growing evidence supports malfunctioning with age of quality control system. At an older age, accumulation of altered macromolecules and membranes may impair cell functioning; accumulation of altered mitochondria and peroxisomes may boost the yield of ROS per unit of produced energy and accelerate the aging process. Evidence produced that autophagy, an essential part in cell housekeeping during fasting, may help removal of altered membranes, mitochondria and peroxisomes selectively and account for the antiaging effects of caloric restriction. Stimulation of autophagy may improve innate and adaptive immunity; decrease the risk of myopathy, heart disease, liver disease, neurodegeneration and cancer; and retard aging. Functioning of autophagy may decline in well fed adults and is almost negligible at older age. Induction of autophagy may result in "cleaner cells" lower in oxidative status and more resistant to injury and disease. The administration of antilipolytic drugs to fasted animals was shown to intensify autophagy in a physiologically appropriate manner, to enhance submaximal antiaging effects of low level of caloric restriction, to rapidly rescue older cells from the accumulation of altered mtDNA and older peroxisomes, to increase urinary 8-OHdG levels, and counteract the age-related hypercholesterolemia in rodents. In conclusion, benefits of long-lasting stimulation of autophagy and protein and organelle turnover shows that antilipolytic drugs might find a novel therapeutic application in antiaging medicine.

Oxidative stress early in infancy and neurodevelopmental outcome in very low‐birthweight infants

Reactive oxygen species may be involved in serious diseases in premature infants. The objective of this study was to assess the relationship between neurodevelopmental outcome and oxidative stress marker level in the urine of very low-birthweight (VLBW) infants. Spot urine samples were collected from 35 VLBW infants. Urinary excretion of 8-hydroxy-2″-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, and 8-iso-prostaglandin F2α (8-isoPGF), a marker of lipid peroxidation, was measured at 1, 2, 4, and 6 weeks of age. Neurodevelopmental outcome at 18 months' corrected age was assessed using the Bayley Scales of Infant Development (BSID)-II. Significant correlations were found between urinary 8-OHdG at 2 and 4 weeks and the Mental Development Index of the BSID-II. No significant correlation was found between urinary 8-isoPGF and indices of the BSID-II. In VLBW infants, urinary 8-OHdG level correlated with mental development rather than psychomotor development at 18 months' corrected age; urinary 8-OHdG might be a predictive marker of neurodevelopmental outcome in VLBW infants.

The Effect of Lithospermic Acid, an Antioxidant, on Development of Diabetic Retinopathy in Spontaneously Obese Diabetic Rats

BackgroundLithospermic acid B (LAB), an active component isolated from Salvia miltiorrhiza radix, has been reported to have antioxidant effects. We examined the effects of LAB on the prevention of diabetic retinopathy in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes.Methods and FindingsLAB (10 or 20 mg/kg) or normal saline were given orally once daily to 24-week-old male OLETF rats for 52 weeks. At the end of treatment, fundoscopic findings, vascular endothelial growth factor (VEGF) expression in the eyeball, VEGF levels in the ocular fluid, and any structural abnormalities in the retina were assessed. Glucose metabolism, serum levels of high-sensitivity C-reactive protein (hsCRP), monocyte chemotactic protein-1 (MCP1), and tumor necrosis factor-alpha (TNFα) and urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels were also measured. Treatment with LAB prevented vascular leakage and basement membrane thickening in retinal capillaries in a dose-dependent manner. Insulin resistance and glucose intolerance were significantly improved by LAB treatment. The levels of serum hsCRP, MCP1, TNFα, and urinary 8-OHdG were lower in the LAB-treated OLETF rats than in the controls.ConclusionsTreatment with LAB had a preventive effect on the development of diabetic retinopathy in this animal model, probably because of its antioxidative effects and anti-inflammatory effects.

0061 Epidemiological study of lung inflammation and oxidative damage in indium tin oxide workers

ObjectivesIndium Tin Oxide (ITO) is widely used in many kinds of touch panels nowadays. Workers could expose to ITO particles from sintering granules, splashing, pulverisation, cutting, and grinding processes. This...

Oxidative stress of office workers relevant to tobacco smoking and inner air quality.

Studies have used 8-hydroxydeoxyguanosine (8-OHdG) as a biomarker to detect systemic oxidative DNA damage associated with oxidative stress. However, studies on the association between exposure to tobacco smoking and urinary 8-OHdgG give inconsistent results. Limited studies have estimated the oxidative stress among office workers. This study assessed the association between urinary 8-OHdG and cotinine for office workers. Workers (389) including smokers, ex-smokers and non-smokers from 87 offices at high-rise buildings in Taipei participated in this study with informed consent. Each participant completed a questionnaire and provided a spot urine specimen at the end of work day for measuring urinary 8-OHdG and cotinine. The carbon dioxide (CO2) levels in workers’ offices were also measured. The questionnaire reported socio-demographic characteristics, life styles and allergic history. The urinary 8-OHdG level increased with the cotinine level among participants (Spearmans’ rho = 0.543, p < 0.001). The mean of urinary 8-OHdG and cotinine was 5.81 ± 3.53 μg/g creatinine and 3.76 ± 4.06 μg/g creatinine, respectively. Comparing with non-smokers, the adjusted odds ratio (OR) of having urinary 8-OHdG greater than the median level of 4.99 μg/g creatinine was 5.30 (95% confidence intervals (CI) = 1.30–21.5) for current smokers and 0.91 (95% CI = 0.34–2.43) for former smokers. We also found workers exposed to 1,000 ppm of CO2 at offices had an adjusted OR of 4.28 (95% CI = 1.12–16.4) to have urinary 8-OHdG greater than 4.99 μg/g creatinine, compared to those exposed to indoor CO2 under 600 ppm. In conclusion, urinary 8-OHdG could represent a suitable marker for measuring smoking and CO2 exposure for office workers.

The reliability and predictive ability of a biomarker of oxidative DNA damage on functional outcomes after stroke rehabilitation.

We evaluated the reliability of 8-hydroxy-2′-deoxyguanosine (8-OHdG), and determined its ability to predict functional outcomes in stroke survivors. The rehabilitation effect on 8-OHdG and functional outcomes were also assessed. Sixty-one stroke patients received a 4-week rehabilitation. Urinary 8-OHdG levels were determined by liquid chromatography–tandem mass spectrometry. The test-retest reliability of 8-OHdG was good (interclass correlation coefficient = 0.76). Upper-limb motor function and muscle power determined by the Fugl-Meyer Assessment (FMA) and Medical Research Council (MRC) scales before rehabilitation showed significant negative correlation with 8-OHdG (r = −0.38, r = −0.30; p < 0.05). After rehabilitation, we found a fair and significant correlation between 8-OHdG and FMA (r = −0.34) and 8-OHdG and pain (r = 0.26, p < 0.05). Baseline 8-OHdG was significantly correlated with post-treatment FMA, MRC, and pain scores (r = −0.34, −0.31, and 0.25; p < 0.05), indicating its ability to predict functional outcomes. 8-OHdG levels were significantly decreased, and functional outcomes were improved after rehabilitation. The exploratory study findings conclude that 8-OHdG is a reliable and promising biomarker of oxidative stress and could be a valid predictor of functional outcomes in patients. Monitoring of behavioral indicators along with biomarkers may have crucial benefits in translational stroke research.

Exposure to polycyclic aromatic hydrocarbons could cause their oxidative DNA damage: a case study for college students in Guangzhou, China

Human exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs) in cigarette smoking might result in generation of reactive oxygen species (ROS) and induce formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG). This study was designed to examine whether levels of 8-OHdG are associated with levels of urinary metabolites of PAHs. Two groups (smokers and non-smokers) were recruited from college students in Guangzhou, China. Their urine samples were collected and analyzed for ten urinary mono-hydroxylated PAHs (OH-PAHs) and 8-OHdG by liquid chromatography equipped with tandem mass spectrometer (LC/MS/MS). Multiple linear regression analysis was performed to examine correlations between urinary levels of 8-OHdG and OH-PAHs. No significant difference was observed for creatinine-adjusted OH-PAHs between smokers and non-smokers. The levels of 8-OHdG between smokers and non-smokers were comparative. OH-PAH levels in this study were 2-50 times higher than those in populations from other countries and areas. The estimated daily intake (EDI; μg/day) of PAHs ranged from 0.02 to 371.4, which were far lower than the reference doses (RfDs) specified by U.S. Environmental Protection Agency (EPA). Though smoking was a main factor, which affected the PAH exposure, it was not a dominant factor in the exposure to PAHs of Guangzhou college students. The environmental exposure could not be ignored. The sum concentrations of OH-PAHs (∑OH-PAHs) had a dose-increase relationship with 8-OHdG both for smokers and non-smokers, especially for smokers. Though people in Guangzhou bore higher PAH hazards, the estimated environmental risk was still under safe ranges.

Association between urinary 8-OHdG and pulse wave velocity in hypertensive patients with type 2 diabetes mellitus.

Oxidative stress, assessed using 8-hydroxy-2'-deoxyguanosine (8-OHdG), can be associated with arterial stiffness in patients with type 2 diabetes mellitus (T2DM) and/or hypertension (HT). We investigated the correlation between urinary 8-OHdG and pulse wave velocity (PWV) in hypertensive and non-hypertensive T2DM patients with fair glycaemic control to determine the clinical significance of HT as a comorbidity in the diabetic state. Clinical data, including traditional cardiovascular risk factors, diabetic complications, prescribed agents, urinary 8-OHdG level and brachial-ankle PWV, was collected from T2DM patients with and without HT. There were 76 patients (45 men, 31 women; mean age 61 years; mean haemoglobin A1c level 6.5%) in the study cohort. T2DM patients with HT had significantly higher mean PWV than patients without HT (1,597 cm/s vs 1,442 cm/s; p < 0.05). Patients with HT showed no significant difference in 8-OHdG levels relative to those without HT (median 7.9 ng/mg creatinine vs 8.8 ng/mg creatinine; p > 0.05). Simple linear correlation and stepwise multiple linear regression analyses revealed that 8-OHdG levels correlated independently, significantly and positively with PWV among T2DM patients with HT (r = 0.33, p < 0.05; β= 0.23, p < 0.05). No significant correlation was observed between 8-OHdG levels and PWV among T2DM patients without HT. In the hypertensive state, oxidative stress can be responsible for the development of arterial stiffness, even in patients with fairly well controlled T2DM. Oxidative stress management may be necessary for the prevention of cardiovascular disease in this population.

Women are more susceptible than men to oxidative stress and chromosome damage caused by polycyclic aromatic hydrocarbons exposure

Exposure to environmental polycyclic aromatic hydrocarbons (PAHs) has been associated with increased risk of cancer, but evidence for gender differences in this association is limited. The aim of this study was to examine the gender differences in PAHs caused early genotoxic effects such as oxidative stress and chromosome damage, which are potential carcinogenic etiology of PAHs. A total of 478 nonsmoking workers (272 men and 206 women) from a coke oven plant were recruited. We determined 16 environmental PAHs in their workplaces, and measured concentrations of 12 urinary PAH metabolites (OH-PAHs), plasma benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydotetrol-albumin (BPDE-Alb) adducts, urinary 8-hydroxydeoxyguanosine (8-OHdG) and 8-iso-prostaglandin-F2α (8-iso-PGF2α), and micronucleus frequencies in lymphocytes in all subjects. It showed that, women working at the office, adjacent to the coke oven, and on the bottom or side of the coke oven displayed significantly higher levels of urinary 8-OHdG and 8-iso-PGF2α, and lymphocytic micronucleus frequencies compared with men working at above areas, respectively (all P < 0.05). These gender differences remain significant after adjusted for potential confounders and urinary ΣOH-PAHs or plasma BPDE-Alb adducts. A significant interaction existed between gender and BPDE-Alb adducts on increasing micronucleus frequencies (Pinteraction < 0.001). We further stratified all workers by the tertiles of urinary ΣOH-PAHs or plasma BPDE-Alb adducts, and the above gender differences were more evident in the median- and high-exposure groups (all P < 0.05). In conclusion, women were more susceptible than men to oxidative stress and chromosome damage induced by PAHs, which may add potential evidence underlying gender differences in PAH exposure-related lung cacinogenesis.

Nanoencapsulation of DMSA monoester for better therapeutic efficacy of the chelating agent against arsenic toxicity.

Exposure to toxic metals remains a widespread occupational and environmental problem in world. Chelation therapy is a mainstream treatment used to treat heavy metal poisoning. This paper describes the synthesis, characterization and therapeutic evaluation of monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA)-encapsulated polymeric nanoparticles as a detoxifying agent for arsenic poisoning. Polymeric nanoparticles entrapping the DMSA monoester, which can evade the reticulo-endothelial system and have a long circulation time in the blood, were prepared. Particle characterization was carried out by transmission electron microscopy and dynamic light scattering. An in vivo study was conducted to investigate the therapeutic efficacy of MiADMSA-encapsulated polymeric nanoparticles (nano- MiADMSA; 50 mg/kg orally for 5 days) and comparison drawn with bulk MiADMSA. Swiss albino mice exposed to sodium arsenite for 4 weeks were treated for 5 days to evaluate alterations in blood, brain, kidney and liver oxidative stress variables. The study also evaluated the histopathological changes in tissues and the chelating potential of the nanoformulation. Our results show that nano-MiADMSA have a narrow size distribution in the 50-nm range. We observed an enhanced chelating potential of nano-MiADMSA compared with bulk MiADMSA as evident in the reversal of biochemical changes indicative of oxidative stress and efficient removal of arsenic from the blood and tissues. Histopathological changes and urinary 8-OHdG levels also prove better therapeutic efficacy of the novel formulation for arsenic toxicity. The results from our study show better therapeutic efficacy of nano-MiADMSA in removing arsenic burden from the brain and liver.