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Oxidative DNA damage markers (8OHdG, comet assay, gammaH2AX) are becoming widely used in clinical cardiology research. To conduct this review of DNA damage in relation to hypertension in humans, we used databases (e.g. PubMed, Web of Science) to search for English-language publications up to June 30, 2022 and the terms: DNA damage, comet assay, gammaH2AX, 8OHdG, strand breaks, and arterial hypertension. Exclusion criteria were: children, absence of relevant controls, extra-arterial hypertensive issues, animal, cell lines. From a total of 79526, 15 human studies were selected. A total of 902 hypertensive patients (pts): (comet: N=418 pts; 8OHdG: N=484 pts) and 587 controls (comet: N=203; 8OHdG: N=384) were included. DNA damage was significantly higher in hypertensive pts than healthy controls (comet 26.6±11.0 vs 11.7±4.07 arbitrary units /A.U./; P P

Introduction. Peritoneal dialysis (PD) is an effective treatment modality for advanced kidney failure, offering patients a significant degree of independence. However, the long-term use of PD is limited due to the degeneration of the peritoneal membrane, resulting in reduced dialysis adequacy. Evaluating the peritoneal membrane condition in patients with advanced kidney failure who are undergoing PD is challenging with existing methods. Therefore, this study aimed to investigate the correlation between 8-hydroxy-2'-deoxyguanosine (8OHDG) levels in the peritoneal solution of patients undergoing PD and various factors, such as peritoneal equilibration test (PET), dialysis adequacy (Kt/V), underlying diseases, serum ferritin, and albumin levels. 8OHDG is a sensitive marker of oxidative stress caused by DNA damage. Methods. A total of 56 patients were included in this cross-sectional study. Five milliliters of PD fluid were collected from the patients, and 8-OHdG levels were measured using ELISA method. Then, they were compared with PET, Kt/V, albumin, and ferritin markers in the patients' files, and the results were analyzed by statistical tests. Results. The study examined the correlation between 8OHDG and other markers. It was found that this index had significant associations with PET and underlying HTN (P < .05), whereas no significant associations were identified with the other markers. Conclusion. The results of the present study demonstrate that the level of 8OHDG, as one of the oxidative stress markers, could be used to evaluate the function of the peritoneum in patients undergoing PD. [ABSTRACT FROM AUTHOR]

Oxidative DNA damage markers (8OHdG, comet assay, gammaH2AX) are becoming widely used in clinical cardiology research. To conduct this review of DNA damage in relation to hypertension in humans, we used databases (e.g. PubMed, Web of Science) to search for English-language publications up to June 30, 2022 and the terms: DNA damage, comet assay, gammaH2AX, 8OHdG, strand breaks, and arterial hypertension. Exclusion criteria were: children, absence of relevant controls, extra-arterial hypertensive issues, animal, cell lines. From a total of 79526, 15 human studies were selected. A total of 902 hypertensive patients (pts): (comet: N=418 pts; 8OHdG: N=484 pts) and 587 controls (comet: N=203; 8OHdG: N=384) were included. DNA damage was significantly higher in hypertensive pts than healthy controls (comet 26.6±11.0 vs 11.7±4.07 arbitrary units/A.U./; P<0.05 and 8OHdG 13.1±4.12 vs 6.97±2.67 ng/mg creatinine; P<0.05) confirmed with meta-analysis for both. Greater DNA damage was observed in more adverse cases (concentric cardiac hypertrophy 43.4±15.4 vs 15.6±5.5; sustained/untreated hypertension 31.4±12.1 vs 14.2±5/35.0±5.0 vs 25.0 ±5.0; non-dippers 39.2±15.5 vs 29.4±11.1 A.U.; elderly 14.9±4.5 vs 9.3±4.1 ng/mg creatinine; without carvedilol 9.1±4.2 vs 5.7±3.9; with coronary heart disease 0.5±0.1 vs 0.2±0.1 ng/mL) (P<0.05) confirmed with meta-analysis. DNA damage correlated strongly positively with serum glycosylated haemoglobin (r=0.670; P<0.05) and negatively with total antioxidant status (r=-0.670 to -0.933; P<0.05). This is the first systematic review with meta-analysis showing that oxidative DNA damage was increased in humans with arterial hypertension compared to controls. [ABSTRACT FROM AUTHOR]

INTRODUCTION: While Alzheimer's disease (AD) is defined by amyloid‐β plaques and tau tangles in the brain, it is evident that many other pathophysiological processes such as inflammation, neurovascular dysfunction, oxidative stress, and metabolic derangements also contribute to the disease process and that varying contributions of these pathways may reflect the heterogeneity of AD. Here, we used a previously validated panel of cerebrospinal fluid (CSF) biomarkers to explore the degree to which different pathophysiological domains are dysregulated in AD and how they relate to each other. METHODS: Twenty‐five CSF biomarkers were analyzed in individuals with a clinical diagnosis of AD verified by positive CSF AD biomarkers (AD, n = 54) and cognitively unimpaired controls negative for CSF AD biomarkers (CU‐N, n = 26) using commercial single‐ and multi‐plex immunoassays. RESULTS: We noted that while AD was associated with increased levels of only three biomarkers (MMP‐10, FABP3, and 8OHdG) on a group level, half of all AD participants had increased levels of biomarkers belonging to at least two pathophysiological domains reflecting the diversity in AD. LASSO modeling showed that a panel of FABP3, 24OHC, MMP‐10, MMP‐2, and 8OHdG constituted the most relevant and minimally correlated set of variables differentiating AD from CU‐N. Interestingly, factor analysis showed that two markers of metabolism and oxidative stress (24OHC and 8OHdG) contributed independent information separate from MMP‐10 and FABP3 suggestive of two independent pathophysiological pathways in AD, one reflecting neurodegeneration and vascular pathology, and the other associated with metabolism and oxidative stress. DISCUSSION: Better understanding of the heterogeneity among individuals with AD and the different contributions of pathophysiological processes besides amyloid‐β and tau will be crucial for optimizing personalized treatment strategies. Highlights: A panel of 25 highly validated biomarker assays were measured in CSF.MMP10, FABP3, and 8OHdG were increased in AD in univariate analysis.Many individuals with AD had increased levels of more than one biomarker.Markers of metabolism and oxidative stress contributed to an AD multianalyte profile.Assessing multiple biomarker domains is important to understand disease heterogeneity. [ABSTRACT FROM AUTHOR]

Abstract INTRODUCTION While Alzheimer's disease (AD) is defined by amyloid‐β plaques and tau tangles in the brain, it is evident that many other pathophysiological processes such as inflammation, neurovascular dysfunction, oxidative stress, and metabolic derangements also contribute to the disease process and that varying contributions of these pathways may reflect the heterogeneity of AD. Here, we used a previously validated panel of cerebrospinal fluid (CSF) biomarkers to explore the degree to which different pathophysiological domains are dysregulated in AD and how they relate to each other. METHODS Twenty‐five CSF biomarkers were analyzed in individuals with a clinical diagnosis of AD verified by positive CSF AD biomarkers (AD, n = 54) and cognitively unimpaired controls negative for CSF AD biomarkers (CU‐N, n = 26) using commercial single‐ and multi‐plex immunoassays. RESULTS We noted that while AD was associated with increased levels of only three biomarkers (MMP‐10, FABP3, and 8OHdG) on a group level, half of all AD participants had increased levels of biomarkers belonging to at least two pathophysiological domains reflecting the diversity in AD. LASSO modeling showed that a panel of FABP3, 24OHC, MMP‐10, MMP‐2, and 8OHdG constituted the most relevant and minimally correlated set of variables differentiating AD from CU‐N. Interestingly, factor analysis showed that two markers of metabolism and oxidative stress (24OHC and 8OHdG) contributed independent information separate from MMP‐10 and FABP3 suggestive of two independent pathophysiological pathways in AD, one reflecting neurodegeneration and vascular pathology, and the other associated with metabolism and oxidative stress. DISCUSSION Better understanding of the heterogeneity among individuals with AD and the different contributions of pathophysiological processes besides amyloid‐β and tau will be crucial for optimizing personalized treatment strategies. Highlights A panel of 25 highly validated biomarker assays were measured in CSF. MMP10, FABP3, and 8OHdG were increased in AD in univariate analysis. Many individuals with AD had increased levels of more than one biomarker. Markers of metabolism and oxidative stress contributed to an AD multianalyte profile. Assessing multiple biomarker domains is important to understand disease heterogeneity.

In SARSCoV-2 infections, excessive activation of the immune system dramatically elevates reactive oxygen species levels, harms cell structures, and directly increases disease severity and mortality. We aimed to evaluate whether plasma oxidative stress biomarker levels could predict mortality in adults admitted with Coronavirus Disease 2019 (COVID-19), considering potential confounders. We conducted a cohort study of 115 adults (62.1 ± 17.6 years, 65 males) admitted to a Brazilian public hospital for severely symptomatic COVID-19. Serum levels of α-tocopherol, glutathione, superoxide dismutase, 8-hydroxy-2′-deoxyguanosine, malondialdehyde, and advanced oxidation protein products were quantified at COVID-19 diagnosis using real-time polymerase chain reaction. Serum levels of α-tocopherol, glutathione, superoxide dismutase, and advanced oxidation protein products differed significantly between survivors and non-survivors. Serum glutathione levels below 327.2 μmol/mL were associated with a significant risk of death in COVID-19 patients, even after accounting for other factors (adjusted hazard ratio = 3.12 [95% CI: 1.83–5.33]). [Display omitted] • COVID-19 leads to an imbalance in the production of ROS and antioxidants. • Oxidative biomarkers can forecast the odds of death in severe COVID-19 patients. • GSH and SOD have shown the highest accuracy in predicting death. • COVID-19 patients with GSH <327.2 μmol/mL face three times the mortality risk. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study is to investigate whether consumption of sturgeon fillets reduces the oxidative stress marker urinary 8‐hydroxy‐2′‐deoxyguanosine (8OHdG) in top‐ranked Japanese female long‐distance runners. Methods: In a before‐and‐after study, nine professional long‐distance female athletes ate 100 g/day of sturgeon fillets for 2 weeks. Urinalysis (8OHdG, an oxidative stress marker, and creatinine), blood tests (fatty acids and 25‐hydroxyvitamin D [25OHD]), exercise intensity, subjective fatigue, muscle elasticity, muscle mass, body fat mass, and nutritional intake using image‐based dietary assessment (IBDA) were compared before, immediately after, and 1 month after the intervention. Results: Consumption of sturgeon fillets suppressed 8OHdG (p < 0.05) in the increased exercise intensity female athletes. Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and 25OHD levels in blood increased from before to immediately after and 1 month after the intervention (p < 0.05). IBDA showed that intake of n‐3 fatty acid increased after and one month after the intervention, whereas DHA, imidazole dipeptide and vitamin D intake increased after the intervention (p < 0.05) and then decreased after 1 month (p < 0.05). There were no significant changes in subjective fatigue, muscle elasticity, muscle mass, and body fat. Conclusions: The results suggest that eating sturgeon fillets during intense training may increase blood levels of EPA, DHA, and 25OHD, which may suppress urinary oxidative stress (8OHdG) in top‐ranked Japanese long‐distance runners. [ABSTRACT FROM AUTHOR]

The hormonal form of vitamin D3, 1,25(OH)2D3, reduces UV-induced DNA damage. UV exposure initiates pre-vitamin D3 production in the skin, and continued UV exposure photoisomerizes pre-vitamin D3 to produce "over-irradiation products" such as lumisterol3 (L3). Cytochrome P450 side-chain cleavage enzyme (CYP11A1) in skin catalyzes the conversion of L3 to produce three main derivatives: 24-hydroxy-L3 [24(OH)L3], 22-hydroxy-L3 [22(OH)L3], and 20,22-dihydroxy-L3 [20,22(OH)L3]. The current study investigated the photoprotective properties of the major over-irradiation metabolite, 24(OH)L3, in human primary keratinocytes and human skin explants. The results indicated that treatment immediately after UV with either 24(OH)L3 or 1,25(OH)2D3 reduced UV-induced cyclobutane pyrimidine dimers and oxidative DNA damage, with similar concentration response curves in keratinocytes, although in skin explants, 1,25(OH)2D3 was more potent. The reductions in DNA damage by both compounds were, at least in part, the result of increased DNA repair through increased energy availability via increased glycolysis, as well as increased DNA damage recognition proteins in the nucleotide excision repair pathway. Reductions in UV-induced DNA photolesions by either compound occurred in the presence of lower reactive oxygen species. The results indicated that under in vitro and ex vivo conditions, 24(OH)L3 provided photoprotection against UV damage similar to that of 1,25(OH)2D3. [ABSTRACT FROM AUTHOR]

Inhalation of nanoparticles emitted from toner-based printing equipment (TPE), such as laser printers and photocopiers, also known as PEPs, has been associated with systemic inflammation, hypertension, cardiovascular disease, respiratory disorders, and genotoxicity. Global serum metabolomics analysis in 19 healthy TPE operators found 52 dysregulated biomolecules involved in upregulation of inflammation, immune, and antioxidant responses and downregulation of cellular energetics and cell proliferation. Here, we build on the metabolomics study by investigating the association of a panel of nine urinary OS biomarkers reflecting DNA/RNA damage (8OHdG, 8OHG, and 5OHMeU), protein/amino acid oxidation (o-tyrosine, 3-chlorotyrosine, and 3-nitrotyrosine), and lipid oxidation (8-isoprostane, 4-hydroxy nonenal, and malondialdehyde [MDA]), as well as plasma total MDA and total protein carbonyl (TPC), with several nanoparticle exposure metrics in the same 19 healthy TPE operators. Plasma total MDA, urinary 5OHMeU, 3-chlorotyrosine, and 3-nitrotyrosine were positively, whereas o-tyrosine inversely and statistically significantly associated with PEPs exposure in multivariate models, after adjusting for age and urinary creatinine. Urinary 8OHdG, 8OHG, 5OHMeU, and total MDA in urine and plasma had group mean values higher than expected in healthy controls without PEPs exposure and comparable to those of workers experiencing low to moderate levels of oxidative stress (OS). The highest exposure group had OS biomarker values, most notably 8OHdG, 8OHG, and total MDA, that compared to workers exposed to welding fumes and titanium dioxide. Particle number concentration was the most sensitive and robust exposure metric. A combination of nanoparticle number concentration and OS potential of fresh aerosols is recommended for larger scale future studies. [ABSTRACT FROM AUTHOR]

The hormonal form of vitamin D3, 1,25(OH)2D3, reduces UV-induced DNA damage. UV exposure initiates pre-vitamin D3 production in the skin, and continued UV exposure photoisomerizes pre-vitamin D3 to produce “over-irradiation products” such as lumisterol3 (L3). Cytochrome P450 side-chain cleavage enzyme (CYP11A1) in skin catalyzes the conversion of L3 to produce three main derivatives: 24-hydroxy-L3 [24(OH)L3], 22-hydroxy-L3 [22(OH)L3], and 20,22-dihydroxy-L3 [20,22(OH)L3]. The current study investigated the photoprotective properties of the major over-irradiation metabolite, 24(OH)L3, in human primary keratinocytes and human skin explants. The results indicated that treatment immediately after UV with either 24(OH)L3 or 1,25(OH)2D3 reduced UV-induced cyclobutane pyrimidine dimers and oxidative DNA damage, with similar concentration response curves in keratinocytes, although in skin explants, 1,25(OH)2D3 was more potent. The reductions in DNA damage by both compounds were, at least in part, the result of increased DNA repair through increased energy availability via increased glycolysis, as well as increased DNA damage recognition proteins in the nucleotide excision repair pathway. Reductions in UV-induced DNA photolesions by either compound occurred in the presence of lower reactive oxygen species. The results indicated that under in vitro and ex vivo conditions, 24(OH)L3 provided photoprotection against UV damage similar to that of 1,25(OH)2D3.

Background: Opioids have been implicated to induce infertility. Although codeine remains the most used opioid for recreational purpose, no study has documented its effect on sperm quality. Elucidating the effect of codeine on sperm cells and the associated mechanisms may provide an insight into preventing drug-induced sperm damage. Twenty-one New Zealand white rabbits were randomized into three groups; control and codeine-treated. The codeine-treated groups received either 4 or 10mg/kg b.w of codeine for six weeks. Results: Codeine treatment led to significant decrease in sperm count, motility, viability, normal morphology, and sperm membrane integrity. This was associated with significant rise in sperm DNA fragmentation, oxidative damage, and caspase 3 activity. The percentage of sperm DNA fragmentation correlates positively with 8-hydroxy-2'-deoxyguanosine, a biomarker of oxidative DNA damage, and caspase 3 activity, a biomarker of apoptosis. The observed correlation was stronger between sperm DNA fragmentation and oxidative DNA damage than sperm DNA fragmentation and caspase 3 activity. Conclusion: This study revealed that chronic codeine exposure causes sperm DNA fragmentation and poor sperm quality primarily via oxidative stress rather than activation of caspase 3-dependent apoptosis. Findings of the present study may explain drug-induced male factor infertility, particularly, those associated with opioid use.

Purpose: In this study, we aimed to explain the role of oxidative stress in women with overactive bladder (OAB) by investigating the levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, and malondialdehyde (MDA), an indicator of lipid peroxidation. Materials and Methods: A total of 90 women were included in the study: 45 female patients diagnosed with OAB at Hopa State Hospital Urology Polyclinic and 45 healthy women without any metabolic or neurologic disease. Levels of MDA and 8-OHdG were measured in 24-hour urine samples for all subjects. Results: Urinary levels of MDA and 8-OHdG were significantly higher in the OAB group than in the control group (p

Background: Opioids have been implicated to induce infertility. Although codeine remains the most used opioid for recreational purpose, no study has documented its effect on sperm quality. Elucidating the effect of codeine on sperm cells and the associated mechanisms may provide an insight into preventing drug-induced sperm damage. Twenty-one New Zealand white rabbits were randomized into three groups; control and codeine-treated. The codeine-treated groups received either 4 or 10mg/kg b.w of codeine for six weeks. Results: Codeine treatment led to significant decrease in sperm count, motility, viability, normal morphology, and sperm membrane integrity. This was associated with significant rise in sperm DNA fragmentation, oxidative damage, and caspase 3 activity. The percentage of sperm DNA fragmentation correlates positively with 8-hydroxy-2'-deoxyguanosine, a biomarker of oxidative DNA damage, and caspase 3 activity, a biomarker of apoptosis. The observed correlation was stronger between sperm DNA fragmentation and oxidative DNA damage than sperm DNA fragmentation and caspase 3 activity. Conclusion: This study revealed that chronic codeine exposure causes sperm DNA fragmentation and poor sperm quality primarily via oxidative stress rather than activation of caspase 3-dependent apoptosis. Findings of the present study may explain drug-induced male factor infertility, particularly, those associated with opioid use. [ABSTRACT FROM AUTHOR]

Purpose: In this study, we aimed to explain the role of oxidative stress in women with overactive bladder (OAB) by investigating the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, and malondialdehyde (MDA), an indicator of lipid peroxidation. Materials and Methods: A total of 90 women were included in the study: 45 female patients diagnosed with OAB at Hopa State Hospital Urology Polyclinic and 45 healthy women without any metabolic or neurologic disease. Levels of MDA and 8-OHdG were measured in 24-hour urine samples for all subjects. Results: Urinary levels of MDA and 8-OHdG were significantly higher in the OAB group than in the control group (p<0.001). A significant positive correlation (p<0.001) was found between the measurements of 8-OHdG and MDA. Conclusions: Oxidative stress may be important in the pathophysiology of OAB, because levels of 8-OHdG and MDA are increased. Increased levels of 8-OHdG may be due to damaged nuclear and mitochondrial DNA as a result of oxidative attacks caused by free radicals. Nevertheless, further randomized and prospective studies with larger patient populations are needed. [ABSTRACT FROM AUTHOR]

Aromatic amines (AAs) are polar organic chemicals with a wide environmental distribution originating from various sources, such as tobacco smoke, diesel exhaust, and dermal absorption from textile products with azo dyes. The toxicity profile of AAs is directly related to the amino group's metabolic activation and the generation of the reactive intermediate, forming DNA adducts and potential carcinogenicity. Urinary levels of 8-hydroxy-2′-deoxyguanosine (8OHdG) are an important biomarker of DNA damage. Since AAs have been shown to cross the placental barrier, being a risk factor for adverse birth outcomes, prenatal exposure is a great public health concern. The present study aimed to measure the urinary levels of 58 AAs in Brazilian pregnant women (n = 300) and investigated the impact of this exposure on DNA damage by quantifying 8OHdG levels. The influence of tobacco smoke exposure and dermal absorption of AAs by clothes on urinary levels was also assessed. The results showed a 100% detection rate for eight AAs, two of them regulated by the European Union (2,6-dimethylaniline and 2,4-diaminotolune). Hundreds of AAs may be derived from aniline, which here showed a median of 1.38 ng/mL. Aniline also correlated positively with 2,6-dimethylaniline, p -aminophenol, and other AAs, suggesting exposure to multiple sources. The present findings suggest that both tobacco smoke and dermal contact with clothes containing azo dyes are potential sources that might strongly influence urinary levels of AAs in Brazilian pregnant women. A multiple regression linear model (R2 = 0.772) suggested that some regulated AAs (i.e., 2-naphthylamine and 4-aminobiphenyl), nicotine, smoke habit, age, and Brazilian region could induce DNA damage occurrence, increasing the levels of 8OHdG. Given the limited available data on human exposure to carcinogenic AAs, as well as the lack of toxicological information on those non-regulated, further studies focused on measuring their levels in human fluids and the potential exposure sources are clearly essential. [Display omitted] • Results showed a detection rate of 100% for eight aromatic amines (two regulated). • Aniline correlates with other aromatic amines, suggesting exposure to multiple sources. • Tobacco smoke and dermal contact with clothes are potential sources of aromatic amines. • Regulated aromatic amines and nicotine can induce DNA damage occurrence. [ABSTRACT FROM AUTHOR]

Purpose: Polycyclic aromatic hydrocarbons (PAHs) are known for their carcinogenic and teratogenic properties. However, little is known about the effect of PAH on our immune and respiratory systems. Hence, we investigated associations (1) between PAH exposure and IgE levels and asthma in children and (2) between PAH exposure and the oxidative stress marker 8OHdG potentially involved in disease pathogenesis stratifying by (3) sex-based differences. Methods: A total of 453 kindergarten children were recruited and provided samples. Urine biomarker of PAH exposure (1-OHP levels) was measured by UPLC-MS/MS and a marker of oxidative stress (8OHdG) was measured by ELISA. Serum IgE were assessed and information on asthma was collected. Associations between 1-OHP levels, 8OHdG, IgE and asthma were analyzed by multivariate linear and logistic regression. A mediation analysis was conducted to evaluate whether the risk of increased IgE and asthma related to PAH exposure is explained by 8OHdG changes. Results: Urine 1-OHP levels were positively related to 8OHdG levels (per ln-unit: β = 0.30kU/l, p = 0.002). Similar results were also found for 1-OHP levels with IgE levels (per ln-unit: β = 0.27 kU/l, p = 0.027). 1-OHP levels (per ln-unit) were significantly associated with asthma, with an OR (95% CI) of 1.42 (1.18-1.70). In addition, 1-OHP levels were associated with asthma. It is estimated that 35% of the effect of PAH exposure on asthma is mediated by 8OHdG levels. Conclusion: Exposure to PAH may enhance oxidative stress and may induce asthma. The effect of PAH exposure on asthma may be mediated by oxidative stress. [ABSTRACT FROM AUTHOR]

Leukocyte 8-hydroxydeoxyguanosine (8OHdG) is an indicator of oxidative stress, impaired metabolism, and mitochondrial dysfunction, features that have been implicated in Huntington disease (HD). Increased levels of 8OHdG have been reported in the caudate, parietal cortex, and peripherally in the serum and leukocytes, in patients diagnosed with HD. However, little is known about levels in prodromal patients and changes that might occur as the disease progresses. To address these issues, 8OHdG was tracked over time for a subset of participants enrolled in the PREDICT-HD study. Participants were stratified into four groups based on proximity to HD diagnosis at study entry: Controls (gene-negative individuals), Low (low probability of near-future diagnosis), Medium, and High. Blood samples were analyzed using Liquid Chromatography Electrochemical Array, and for comparison purposes, a separate cross-sectional sample was analyzed using liquid chromatography coupled with multiple-reaction-monitoring mass spectrometry. Longitudinal data analysis showed that initial status (at study entry) and annual rate of change varied as a function of proximity group, adjusting for sex, education, age at study entry, and site effects. Overall levels were lowest for the Control group and highest for the High group, and the rate of increase varied in a similar manner. The finding that 8OHdG concentrations increased as a function of proximity to projected disease diagnosis and duration indicates support for the continued assessment of 8OHdG as a robust clinical HD biomarker.

As bisphenol A (BPA) exerts oxidative/pro-apoptotic effects in several cell types, we explored whether the in vitro exposure to BPA could affect human sperm integrity through the induction of pro-oxidative/apoptotic mitochondrial dysfunction. The exposure of motile sperm suspensions to scalar BPA concentrations for 4 h produced a decrease in the mitochondrial membrane potential, starting from 300 μM. It was associated with an increased mitochondrial generation of superoxide anion, caspase-9 and caspase-3 activation and motility decrement. Vitality decline was observed at BPA ≥ 400 μM. Twenty hours exposure to 300 μM BPA, but not to lower concentrations, produced a significant loss in sperm vitality associated with a complete sperm immobilization. Finally, 300 μM BPA also produced a significant DNA oxidative damage, as revealed by the formation of oxidized base adduct 8-hydroxy-2′-deoxyguanosine. In conclusion, BPA affected human sperm integrity by inducing pro-oxidative/apoptotic mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

Pioglitazone, an oral hypoglycemic agent, recently failed to show promise as a disease-modifying agent in a 44-week phase 2 placebo-controlled study in 210 Parkinson's disease (PD) subjects. We analyzed peripheral biomarkers, including leukocyte PGC-1α and target gene expression, plasma interleukin 6 (IL-6) as a marker of inflammation, and urine 8-hydroxydeoxyguanosine (8OHdG) as a marker of oxidative DNA damage. Baseline or changes from baseline in biomarker levels were not associated with the rate of progression of PD. Pioglitazone did not significantly alter biomarker levels. Other agents that more effectively target these mechanisms remain of potential interest as disease modifying therapies in PD. [ABSTRACT FROM AUTHOR]

To investigate the relationship between oxidative stress and gastric carcinogenesis of poorly differentiated adenocarcinoma in young patients, we analyzed the surgically resected specimens of 22 young patients (21-30 years) and 29 older patients (41-72 years) with intramucosal gastric cancer of the poorly differentiated type. We used immunohistochemical staining to evaluate the expression of 8-hydroxydeoxyguanosine (8 OHdG), induced nitric oxide synthetase ( iNOS), and antioxidant enzymes (thioredoxin [ TRX] and peroxiredoxin [ PRDX1, 2 and 3]). We assessed these proteins in the cancer, noncancerous gastric foveolar epithelium and noncancerous mucosal neck. In both the young and older patient groups, the 8 OHdG and TRX expressions were gradually increased in cancer cells compared with the noncancerous foveolar epithelial cells and the noncancerous mucosal neck cells ( P < 0.001). Although the i NOS and PRDXs expressions were increased in the noncancerous mucosal neck cells compared with the noncancerous foveolar epithelial cells, regardless of age ( P < 0.001), the iNOS and PRDX2 expression in the cancer cells were significantly reduced in the young patients compared with the older patients ( P < 0.001 , P < 0.05). In conclusion, the reduced expression of i NOS or PRDX2 may play an important role in the carcinogenesis of gastric cancer associated with Helicobacter pylori-induced chronic active gastritis in young patients. [ABSTRACT FROM AUTHOR]

The large-scale use of silver nanoparticles (AgNPs) has raised concerns over potential impacts on the environment and human health. We previously reported that AgNP exposure causes an increase in reactive oxygen species, DNA damage, and induction of p38 MAPK and PMK-1 in Jurkat T cells and in Caenorhabditis elegans. To elucidate the underlying mechanisms of AgNP toxicity, here we evaluate the effects of AgNPs on oxidative DNA damage-repair (in human and C. elegans DNA glycosylases hOGG1, hNTH1, NTH-1, and 8-oxo-GTPases-hMTH1, NDX-4) and explore the role of p38 MAPK and PMK-1 in this process. Our comparative approach examined viability, gene expression, and enzyme activities in wild type (WT) and p38 MAPK knock-down (KD) Jurkat T cells (in vitro) and in WT and pmk-1 loss-of-function mutant strains of C. elegans (in vivo). The results suggest that p38 MAPK/PMK-1 plays protective role against AgNP-mediated toxicity, reduced viability and greater accumulation of 8OHdG was observed in AgNP-treated KD cells, and in pmk-1 mutant worms compared with their WT counterparts, respectively. Furthermore, dose-dependent alterations in hOGG1, hMTH1, and NDX-4 expression and enzyme activity, and survival in ndx-4 mutant worms occurred following AgNP exposure. Interestingly, the absence or depletion of p38 MAPK/PMK-1 caused impaired and additive effects in AgNP-induced ndx-4( ok1003); pmk-1(RNAi) mutant survival, and hOGG1 and NDX-4 expression and enzyme activity, which may lead to higher accumulation of 8OHdG. Together, the results indicate that p38 MAPK/PMK-1 plays an important protective role in AgNP-induced oxidative DNA damage-repair which is conserved from C. elegans to humans. Environ. Mol. Mutagen. 55:122-133, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Exaggerated inflammation and oxidative stress are involved in the pathogenesis of Complex Regional Pain Syndrome (CRPS). However, studies assessing markers for oxidative stress in CRPS patients are limited. In this study, markers for lipid peroxidation (malondialdehyde and F2-isoprostanes) and DNA damage (8-hydroxy-2-deoxyguanosine) were measured in nine patients (mean age 50.1 ± 17.1 years) with short term CRPS-1 (median 3 months) and nine age and sex matched healthy volunteers (mean age 49.3 ± 16.8 years) to assess and compare the level of oxidative stress. No differences were found in plasma between CRPS patients and healthy volunteers for malondialdehyde (5.2 ± 0.9 µmol/L vs. 5.4 ± 0.5 µmol/L) F2-isoprostanes (83.9 ± 18.7 pg/mL vs. 80.5 ± 12.3 pg/mL) and 8-hydroxy-2-deoxyguanosine (92.6 ± 25.5 pmol/L vs. 86.9 ± 19.0 pmol/L). Likewise, in urine, no differences were observed between CRPS patients and healthy volunteers for F2-isoprostanes (117 ng/mmol, IQR 54.5-124.3 vs. 85 ng/mmol, IQR 55.5-110) and 8-hydroxy-2-deoxyguanosine (1.4 ± 0.7 nmol/mmol vs. 1.4 ± 0.5 nmol/mmol). Our data show no elevation of systemic markers of oxidative stress in CRPS patients compared to matched healthy volunteers. Future research should focus on local sampling methods of oxidative stress with adequate patient selection based on CRPS phenotype and lifestyle. [ABSTRACT FROM AUTHOR]

8-Hydroxy-2-deoxyguanosine (8OHdG) excreted into the urine is considered a marker of oxidative stress effect on DNA, and it is reported to be mainly produced by the DNA repair system. In previous works, we showed that autophagy was also involved in 8OHdG disposal through the degradation of oxidatively altered mitochondria. Here, we show that aging in Sprague-Dawley male rats is associated with a decline in the in vitro function of liver autophagy and a slight and not significant decrease in the urinary excretion of 8OHdG. In addition, we demonstrate that anti-aging caloric restriction maintains levels of both liver autophagy and urinary excretion of 8OHdG at very high levels throughout life. Finally, we show the in vivo stimulation of autophagy by the administration of an antilipolytic agent or everolimus, which rescues rats from the accumulation of 8OHdG in the liver mtDNA, also causes a dramatic increase in the urinary excretion of 8OHdG. The intensification of autophagy by the administration of the antilipolytic drugs to fasting rats faded progressively with increasing age, together with a reduced increase in 8OHdG output into the urine. It is concluded that the process of autophagy may play a major role in the disposal of 8OHdG with urine, and that the assay of 8OHdG levels in the urine before and after the stimulation of autophagy may provide a novel, non-invasive and safe procedure to monitor the in vivo functioning of the process. [ABSTRACT FROM AUTHOR]

Background: H. pylori ( Hp) infection is a major risk factor in gastric carcinogenesis leading to epithelial mutagenesis, and may affect gastric epithelial stem cells. Aims: To characterize the expression of Lgr5, a marker of epithelial stem cells in human gastric mucosa, to determine whether Hp infection affects Lgr5-positive epithelial cells (LPECs) and whether LPECs are susceptible to DNA damage associated with Hp infection. Methods: Lgr5 expression was characterized in non-neoplastic gastric mucosa from 52 patients (34 with and 18 without gastric cancer (GC); 21 Hp-positive ( Hp+) and 31 Hp-negative ( Hp−)) by immunohistochemical and immunofluorescence staining. To determine the extent of DNA damage in LPECs, nuclear 8-hydroxydeoxyguanosine (8OHdG), a marker of DNA damage associated with oxidative stress, was measured by quantitative spectral image analysis. Results: LPECs were primarily present in gastric antrum. Higher numbers of LPECs were seen in Hp+ than in Hp− non-neoplastic mucosa of GC patients, P = .006, but not in patients without GC. 8OHdG levels in LPECs were significantly higher than in Lgr5-negative epithelial cells in Hp+ GC patients ( P = .012) but not in Hp− cases ( P = .414), whereas no difference was seen between Hp+ and Hp− mucosa of patients without GC. Conclusions: The Lgr5-positive epithelial stem cell pool is expanded in Hp-associated gastritis in the antrum of patients with GC. In GC patients with active Hp infection, LPECs may be more susceptible to DNA damage than Lgr5-negative epithelial cells, suggesting that Hp infection may contribute to GC risk by affecting epithelial stem cells in the human stomach. [ABSTRACT FROM AUTHOR]

BACKGROUND: Whereas studies have revealed that the cryopreservation of human semen increases sperm DNA fragmentation, the mechanisms involved in this type of cryo-injury are largely unknown. Elucidation of these mechanisms may provide insight into preventing such injury. [ABSTRACT FROM PUBLISHER]

This study investigated the effect of a single dose of tomato sauce on healthy male volunteers in a randomized crossover study. Healthy male subjects (n = 10) were enrolled. Placebo (rice and olive oil) or tomato (tomato sauce, rice and olive oil) meals were provided to the volunteers. Blood and urine samples were taken before consumption of meal (0 h) and 2, 4, 6, 24 and 48 h after meal. Consumption of tomato sauce increased plasma lycopene level by 5-22%, with a maximum level at 24 h (p<0.01) after the meal. Levels of plasma F2-isoprostanes, hydroxyeicosatetraenoic acid products, allantoin and urinary 8-hydroxy-2'-deoxyguanosine did not change after either meal, but urinary F2-isoprostanes (p<0.05) significantly decreased at 48 h compared to 0 h after the tomato sauce meal. This study showed that a single dose of tomato sauce meal had only a limited antioxidant effect in vivo. [ABSTRACT FROM AUTHOR]

Summary: Background and aims: Weight maintenance within normal standards is recommended for prevention of conditions associated with oxidative injury. To compare oxidative damage in a post mitotic tissue, between adults differing in long-term energy balance. Methods: During hernia surgery, a sample of skeletal muscle was obtained in 17 non-obese adults. Subjects were divided into two groups according to their self-reported weight change: weight maintainers (WM) reported <4kg increase, and weight gainers (WG) reported >5kg increment. Muscle immunohistochemistry for 8-hydroxy-deoxyguanosine (8OHdG), 4-Hydroxy-2-nonenal (4HNE), and TNF-α, as markers of oxidative injury and inflammation, were performed. As known positive controls for oxidative injury, we included 10 elderly subjects (66–101yr). Anthropometric measures and blood samples for clinical laboratory and serum cytokines (TNF-α and IL-6) were obtained. Results: 8OHdG was higher in WG compared with WM (149.1±16.2 versus 117.8±29.5, ), and was associated with anthropometric indicators of fat accumulation. 4HNE was similar in WG compared with WM (10.9±7.6 versus 9.8±6.3) but noticeably higher in elderly subjects (21.5±15.3, ). TNF-α protein in WG was higher compared with WM (114.0±41.7 versus 70.1±23.3, ), and was associated with weight increase. Conclusions: Moderate self-reported weight increase, and body fat accumulation, suggesting long-term positive energy balance is associated with muscle DNA oxidative injury and inflammation. [Copyright &y& Elsevier]

The extent of in vivo oxidative damage has been known to be cumulative over the period of the life of mammals. Our hypothesis is that there should be a positive correlation between the levels of 8-hydroxy-2'-deoxyguanosine (8OHdG) and 8-iso-prostaglandin F 2a (8-iso-PGF 2a ) in major rat tissues. We also investigated whether increased level of oxidative stress causes a decrease in the mitochondrial membrane potential of peripheral lymphocytes of old rats using the MitoTracker Red fluorochrome. Our results show positive correlations between 8OHdG and 8-iso-PGF 2a for liver, brain and kidney measured by HPLC-UV-ECD (electrochemical detector) and EIA methods, respectively. However, heart tissues show a negative correlation. The mitochondrial membrane potential of old rat lymphocytes records significant decrease compared with the young lymphocytes. Based on our results, we conclude that in ageing studies, specific tissues need to be examined in order to measure the localised DNA damage and lipid peroxidation as different tissues display different extent of oxidative damage. We believe this approach of using combined markers is useful to verify the true efficacy of health intervention studies in animals and humans. In addition, the isoprostane assay can be further developed looking at lipid peroxidation as a potential marker in ageing studies. [ABSTRACT FROM AUTHOR]

Numerous changes occur post-mortem in fish, affecting its chemical composition and nutritional quality. In the present paper we describe the effect of storage on ice or at -30°C or -80°C on 10 species of Mediterranean fish. Water and lipid soluble antioxidants, lipid pattern and products of oxidative attack on lipids, proteins and DNA were quantified for 7 consecutive days on homogenates of fish light muscle. The earliest events were oxidation of ubiquinol and vitamin C, which disappeared almost completely within 48 hours. Ubiquinol oxidation gave rise to an initial increase of ubiquinone, which peaked at the second day: thereafter ubiquinone itslef decreased, more rapidly and to a greater extent than vitamin E. The decrease in antioxidants was accompanied by significant oxidative damage to lipids, proteins and DNA. TBARS significantly increased beginning from the third day of storage in all species and were linked to a significant reduction in the n-3 PUFA of triglycerides (TG) and phospholipid fractions (PL). A remarkable elevation of protein carbonyls and 8OHdG occurred approximately 24 hours later than PUFA oxidation. For SOD, GPX and GSH significant depletions occurred for all species only at 6th or 7th day, but the final values were always higher than 50% compared to the initial ones. Deep-freezing of the same species at -30°C and -80°C for up to 12 months did not significantly affect the levels of enzymatic antioxidants, the redox couple GSH/GS-SG, n-3 and n-6 PUFA of TG and PL fractions of the light muscle. The only antioxidants, which at -30°C and -80°C appeared to be degraded after 6 and 12 months were ubiquinol and vitamin C. As expected their degradation was higher at -30°C than at -80°C. In fact the average decrease for ubiquinol at -80°C was 42% at 6 and 12 months respectively, whereas at -30°C the decrease was 61% and 87% For vitamin C the average decrease at -80°C was 36% and 67% at 6 and 12 months respectively, and at -30°C it was 61% and 82%. Vitamin E was considerably more stable than ubiquinol and vitamin C. The relative stability of the antioxidants, with the exceptions of ubiquionols, vitamin C and, to a certain extent, vitamin E, was accompanied by a very limited increase in oxidation products. In addition no significant hydrolysis of TG and PL fractions were observed throughout the storage time. The dynamics of lipid, protein and DNA oxidation is discussed in the light of depletion of the various antioxidant systems. [ABSTRACT FROM AUTHOR]

8-Hydroxy-2′-deoxyguanosine (8OHdG) is regarded as an important biomarker of oxidative DNA damage and it may be estimated by using different techniques in various biological matrices, most notably DNA and urine. In the case of DNA, artifactual oxidation may take place during the isolation of DNA, its hydrolysis and possible derivatization (as for GC-MS), invalidating the measurement of 8OHdG. Therefore, the direct analysis of 8OHdG excreted into urine was preferred. Interferences from the urine matrix were excluded by applying LC-APCI-MS/MS in the multiple reaction monitoring (MRM) mode. The abundant fragment ion at m/z 168 arising from 8OHdG was monitored in the urine sample of volunteers supplemented with tomato concentrate for different times. The procedure allowed the detection of levels of 8OHdG as low as 1 ng/ml in urine sample. [Copyright &y& Elsevier]

Ultraviolet B radiation (UVB) induces oxidative damage in DNA, resulting in the formation of the adduct 8-hydroxydeoxyguanosine. Previous studies from this laboratory have demonstrated a decrease in antioxidant enzyme defenses after UVB radiation in Skh: HR-1 hairless mice, implicating antioxidant status in protection against oxidative damage. The present study was undertaken to examine mechanisms of UVB damage to DNA and modulation by vitamin C, selenite, or Trolox™, a water-soluble vitamin E analog. BALB/c MK-2 mouse keratinocytes were exposed to a dose range of UVB from 4 to 750 mJ/cm2. DNA damage in the form of 8OHdG was measured using high-pressure liquid chromatography coupled with electrochemical and UV absorbance detection. Preincubation of the cells for 2 days with 0.4 or 0.8 μg/ml ascorbic acid, 10 or 20 μg/m1 Trolox™, and 5 or 12.5 μM selenite resulted in a significant decrease in the number of 8-hydroxydeoxyguanosine adducts per 105 deoxyguanines induced by 500 mJ/cm2 UVB. The results indicate a potential role for antioxidant nutrients in protection against UVB damage to skin cells. [ABSTRACT FROM AUTHOR]

We analyzed plasma 8OHdG concentrations in 20 individuals enrolled in the Pre-2CARE study before and after treatment with CoQ. Treatment resulted in a mean reduction in 8OHdG of 2.9 ± 2.9 pg/ml for the cohort (p = 0.0003) and 3.0 ± 2.6 pg/ml, for the HD group (p = 0.002). Baseline 8OHdG levels were not different between individuals with HD and controls (19.3 ± 3.2 pg/ml vs. 19.5 ± 4.7 pg/ml, p = 0.87) though baseline CoQ levels were elevated in HD compared with controls (p < 0.001). CoQ treatment reduces plasma 8OHdG and this reduction may serve as a marker of pharmacologic activity of CoQ in HD.