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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. DOI: 10.52547/ijkd.7654.

Exposure to multiple environmental pollutants is ubiquitous and inevitable, but studies investigating their exposure effects on oxidative stress or inflammation have mainly been restricted to single-pollutant models. This study investigated the association of co-exposure to polycyclic aromatic hydrocarbons and phthalates with oxidative stress and inflammation. Using a cross-sectional study in adults, we measured urinary concentrations of metabolites of polycyclic aromatic hydrocarbons (OH-PAHs) and phthalates (mPAEs), urinary oxidative stress biomarker 8-hydroxy-2'-deoxyguanosine, and 9 inflammatory biomarkers in paired blood samples. The associations of urinary OH-PAHs and mPAEs with oxidative stress and inflammation biomarkers were evaluated by different statistical models. The Bayesian kernel machine regression and quantile g-computation was used to examine the joint effects, and increased levels of urinary concentrations of OH-PAHs and mPAEs were associated with elevated 8-hydroxy-2'-deoxyguanosine level and white blood cell counts. Exposure to polycyclic aromatic hydrocarbons contributed more significantly to inflammation, while exposure to phthalates contributed more to oxidative stress. Monoisobutyl phthalate was identified as the most significant metabolite contributing to elevated oxidative stress levels. 1-Hydroxypyrene was negatively associated with platelet, and monomethyl phthalate was significantly positively associated with interleukin 6 in multivariate linear regression. The restricted cubic spline analysis revealed non-linear patterns of 3-hydroxyfluorene with white blood cell, lymphocyte, neutrophil, and C-reactive protein. The results indicated significant associations between increased co-exposure to polycyclic aromatic hydrocarbons and phthalates with elevated oxidative stress and inflammation. Further investigation is needed to elucidate the underlying biological mechanisms and to determine the potential public health implications., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Oxidative stress is a prominent pathway for the health effects associated with fine particulate matter (PM 2.5 ) exposure. Oxidative potential (OP) of PM has been associated to several health endpoints, but studies on its impact on biomarkers of oxidative stress remains insufficient. 300 pregnant women from the SEPAGES cohort (France) carried personal PM 2.5 samplers for a week and OP was measured using ascorbic acid (AA) and dithiothreitol (DTT) assays, and normalized by 1) PM 2.5 mass (OP m ) and 2) sampled air volume (OP v ). A pool of three urine spots collected on the 7th day of PM sampling was analyzed for biomarkers, namely 8-hydroxy-2-deoxyguanosine (8-OHdG), malondialdehyde (MDA) and 8-isoprostaglandin-F2α (8-isoPGF2α). Associations were investigated using adjusted multiple linear regressions. OP effects were additionally investigated by stratifying by median PM 2.5 concentration (14 μg m -3 ). In the main models, no association was observed with 8-isoPGF2α, nor MDA. An interquartile range (IQR) increase in OP m AA exposure was associated with increased 8-OHdG (percent change: 6.2 %; 95 % CI: 0.2 % to 12.6 %). In the stratified analysis, exposure to OP m AA was associated with 8-OHdG for participants exposed to low levels of PM 2.5 (percent change: 11.4 %; 95 % CI: 3.3 % to 20.1 %), but not for those exposed to high levels (percent change: -1.0 %; 95 % CI: -10.6 % to 9.6 %). Associations for OP m DTT also followed a similar pattern (p-values for OP m AA -PM and OP m DTT -PM interaction terms were 0.12 and 0.11, respectively). Overall, our findings suggest that OP m AA may be associated with increased DNA oxidative damage. This association was not observed with PM 2.5 mass concentration exposure. The effects of OP m AA in 8-OHdG tended to be stronger at lower (below median) vs. higher concentrations of PM 2.5 . Further epidemiological, toxicological and aerosol research are needed to further investigate the OP m AA effects on 8-OHdG and the potential modifying effect of PM mass concentration on this association., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Polycyclic aromatic hydrocarbon (PAH) exposure has been associated with adverse health effects, and accumulating evidence suggests that PAH exposure may impair liver function. However, the underlying mechanisms linking PAH exposure and liver function impairment remain unclear. This study aimed to explore the association between PAH exposure and liver function biomarkers, and the mediating effects of inflammation and oxidative stress. The cross-sectional study included 155 adults and their urinary PAH metabolites (OH-PAHs) were determined, and eight liver function biomarkers were measured in paired serum samples. A comprehensive statistical analysis investigated the linear, non-linear, individual, and joint effects of the association between urinary OH-PAHs and liver function biomarkers. The results indicated significant positive associations between urinary OH-PAH concentrations and liver function biomarker levels, suggesting that PAH exposure may adversely affect liver function. 2-hydroxyfluorene was identified as the individual metabolite contributing significantly to elevated gamma-glutamyl transferase levels. Further stratification by gender revealed that this association is more pronounced in males. Moreover, we observed significant mediation effects of the oxidative stress biomarker 8-hydroxy-2'-deoxyguanosine and the inflammatory biomarkers C-reactive protein and white blood cell count on this association. The physiological responses triggered by PAH exposure are mediated by inflammation, which serves as a link between oxidative stress, cellular injury, and elevated liver enzyme levels. The results demonstrated that increased inflammation and oxidative stress mediated the association between increased urinary OH-PAHs and elevated liver function biomarkers. The results contribute to a better understanding of the potential mechanisms underlying PAH exposure's hepatotoxic effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Children are highly vulnerable to environmental pollutants, especially endocrine-disrupting chemicals (EDCs). Previous research has linked both organic UV filters and phthalates exposure to adiposity and pubertal development in children. Nevertheless, the individual and collective effects of these chemicals on this population remain poorly understood. In this study, twelve organic UV filters and metabolites, six phthalate metabolites and two oxidative stress biomarkers were analyzed in a prospective follow-up study in Shanghai, China after a baseline study conducted 1.5 years earlier. Results revealed a positive association between exposure to individual organic UV filters or their mixture and levels of 8-OHdG (β ranging from 0.242 to 0.588, P < 0.05), a marker of oxidative DNA damage. BP-3 and OD-PABA made a greater contribution to oxidative DNA damage than other UV filters. Levels of 8-OHdG were also positively correlated with single phthalate metabolites and their mixture, with MnBP and MMP contributing the most. Stratified analysis found that these associations were mainly observed in girls. Our mixture analysis revealed cumulative risks of oxidative DNA damage when there was co-exposure to these two kinds of EDCs. These results underscore the importance of considering the risks associated with organic UV filters and the necessity of evaluating the effects of all these pollutants, both individually and in mixtures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Epidemiological studies have suggested that phthalate exposures are associated with increased risks of thyroid cancer and benign nodule, while the underlying mechanisms are largely unknown. Here, we explored the mediation effects of oxidative stress (OS) biomarkers in the associations between phthalate exposures and the risks of thyroid cancer and benign nodule. Urine samples collected from 143 thyroid cancer, 136 nodule patients, and 141 healthy controls were analyzed for 8 phthalate metabolites and 3 OS biomarkers [8-hydroxy-2-deoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), and 8-iso-prostaglandin F 2α (8-isoPGF 2α )]. Multivariable linear or logistic regression models were used to explore the associations of OS biomarkers with phthalate metabolite concentrations and the risks of thyroid cancer and nodule. The mediation role of OS biomarkers was also investigated. Urinary monoethyl phthalate (MEP), monomethyl phthalate (MMP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP), mono (2-ethylhexyl) phthalate (MEHP), and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) were positively associated with at least 2 OS biomarkers (all P-values<0.01), and part of these positive associations varied in different subgroups. All 3 OS biomarkers were positively associated with the risks of thyroid nodule and cancer (P-values<0.001). The mediation analysis showed that OS biomarkers significantly mediated the associations between urinary MEHOP concentration and nodule, as well as between urinary MMP, MEHP, and MEHHP concentrations and cancer and nodule, with the estimated proportions of mediation ranging from 15.8% to 85.6%. Our results suggest that OS is a potential mediating mechanism through which phthalate exposures induce thyroid carcinogenesis and nodular formation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: To investigate determinants of oxidative stress in an indigenous population, we examined associations of trace element exposures and dietary patterns with three oxidative stress-related biomarkers among indigenous populations in Northern Laos., Methods: This cross-sectional study included 341 adults from three villages with different levels of modernization. We used three oxidative stress-related biomarkers: urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-isoprostane concentrations, which were measured using liquid chromatography-tandem mass spectrometry, and blood telomere lengths, which were measured using a quantitative polymerase chain reaction method. We used multilevel analysis to examine associations of urinary arsenic, cadmium, and selenium concentrations, their interaction terms, and wild-plant-food scores (principal component scores calculated from food consumption frequencies) with oxidative stress-related biomarkers., Results: Urinary arsenic and cadmium concentrations were positively associated with urinary 8-isoprostane concentrations. Urinary selenium concentrations were positively associated with urinary 8-OHdG concentrations. Interaction terms ([arsenic or cadmium] × selenium) showed negative associations with urinary 8-OHdG and 8-isoprostane concentrations, respectively. Urinary cadmium concentrations were negatively associated with telomere lengths. Wild-plant-food scores did not exhibit associations with oxidative stress-related biomarkers., Conclusion: Our findings imply that exposure to arsenic and cadmium is associated with greater oxidative lipid damage, whereas selenium may attenuate arsenic-induced oxidative DNA damage and cadmium-induced oxidative lipid damage. Cadmium exposure may accelerate telomere attrition. Trace element exposure may be a determinant of oxidative stress among indigenous populations in Northern Laos., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Frequent heavy air pollution occurred during the winter heating season of northern China. Particulate air pollution is a serious concern in Urumqi during heating season. Exposure to air pollution is known to increase adverse health outcomes, particularly oxidative damage. This study aimed to evaluate the impact of air pollution on oxidative damage around pregnant women and newborns in Urumqi., Methods: This prospective observational study enrolled pregnant women in the Fifth Affiliated Hospital of Xinjiang Medical University between January 2019 and October 2019. Pregnant women and newborns were allocated into a heating season group (January - end of April 2019, October 2019) or non-heating season group (June 2019 - end of September) according to the specific delivery time. Venous blood, urine from the women and cord blood from their newborns were collected to measure the levels of PAHs and 8-deoxyguanosine (8-OHdG), a measure of oxidative stress., Results: A total of 200 pregnant women and newborns were enrolled, with 100 pregnant women and newborns in the heating season group. Compared to the non-heating season group, the total contents of 8-OHdG in maternal urine, PAHs and 8-OHdG in maternal plasma and neonatal cord blood were higher in the heating season group (all P < 0.001). The average values for AQI, PM 2.5 , PM 10 , SO 2 , NO 2 , and CO were higher in the heating season group (all P < 0.001). Maternal and neonatal PAHs were correlated with 8-OHdG measurements in maternal urine (r = 0.288, P < 0.001 and r = 0.336, P < 0.001) and neonatal umbilical cord blood (r = 0.296, P < 0.001 and r = 0.252, P < 0.001). There was also a positive relationship between PAHs, 8-OHdG levels in pregnant women and their newborns and proximate air pollutant concentrations (all P < 0.05). Based on the results of multiple linear regression analysis, it was found that air pollutants(PM 10 , 0 3 ) had a great influence on the level of 8-OHdG in neonatal cord blood, and the contribution rate was high(R 2  = 0.320). Based on the epidemiological questionnaire, a multiple linear regression model was established(R 2  = 0.496). We found that 8-OHdG levels in neonatal umbilical cord blood were mainly affected by two aspects: (1) Biological samples collected during heating had higher levels of 8-OHdG in neonatal umbilical cord blood. (2) Study may suggest that in neonates, males are more sensitive to oxidative damage., Conclusion: Particulate air pollution may increase PAHs exposure and oxidative DNA damage in pregnant women and newborns., (© 2023. The Author(s).)

Objectives: The aims of the study are to measure the prevalence and level of occupational stress (OS) and to explore its association with oxidative stress among some brickfield workers., Methods: Eighty-six brickfield workers and 90 administrative controls were assessed using the Arabic validated version of the Occupational Stress Index. The urinary levels of oxidative biomarkers; 8-hydroxy-2'-deoxyguanosine and biopyrrins were also measured., Results: The prevalence of moderate and severe OS in addition to the urinary levels of both oxidative biomarkers was significantly higher among the brickfield workers compared with their controls. Both biomarkers levels were significantly and positively correlated with scores of Occupational Stress Index, duration of employment, and with each other. The receiver operating characteristic analysis showed significant specificity and sensitivity of both biomarkers for determining the level of OS., Conclusions: A significant association between occupational and oxidative stresses was detected in brickfield workers., Competing Interests: Conflict of interest: None declared., (Copyright © 2022 American College of Occupational and Environmental Medicine.)

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.

Adverse health effects driven by airborne particulate matter (PM) are mainly associated with reactive oxygen species formation, pro-inflammatory effects, and genome instability. Therefore, a better understanding of the underlying mechanisms is needed to evaluate health risks caused by exposure to PM. The aim of this study was to compare the genotoxic effects of two oxidizing agents (menadione and 3-chloro-1,2-propanediol) with three different reference PM (fine dust ERM-CZ100, urban dust SRM1649, and diesel PM SRM2975) on monocytic THP-1 and alveolar epithelial A549 cells. We assessed DNA oxidation by measuring the oxidized derivative 8-hydroxy-2'-deoxyguanosine (8-OHdG) following short and long exposure times to evaluate the persistency of oxidative DNA damage. Cytokinesis-block micronucleus cytome assay was performed to assess chromosomal instability, cytostasis, and cytotoxicity. Particles were characterized by inductively coupled plasma mass spectrometry in terms of selected elemental content, the release of ions in cell medium and the cellular uptake of metals. PM deposition and cellular dose were investigated by a spectrophotometric method on adherent A549 cells. The level of lipid peroxidation was evaluated via malondialdehyde concentration measurement. Despite differences in the tested concentrations, deposition efficiency, and lipid peroxidation levels, all reference PM samples caused oxidative DNA damage to a similar extent as the two oxidizers in terms of magnitude but with different oxidative DNA damage persistence. Diesel SRM2975 were more effective in inducing chromosomal instability with respect to fine and urban dust highlighting the role of polycyclic aromatic hydrocarbons derivatives on chromosomal instability. The persistence of 8-OHdG lesions strongly correlated with different types of chromosomal damage and revealed distinguishing sensitivity of cell types as well as specific features of particles versus oxidizing agent effects. In conclusion, this study revealed that an interplay between DNA oxidation persistence and chromosomal damage is driving particulate matter-induced genome instability., (Copyright © 2022 Elsevier B.V. All rights reserved.)

8-Oxo-7,8-dihydro-2'-deoxyguanosine (OG), one of the most common oxidative DNA damages, causes genome instability and is associated with cancer, neurological diseases and aging. In addition, OG and its repair intermediates can regulate gene transcription, and thus play a role in sensing cellular oxidative stress. However, the lack of methods to precisely map OG has hindered the study of its biological roles. Here, we developed a single-nucleotide resolution OG-sequencing method, named CLAPS-seq (Chemical Labeling And Polymerase Stalling Sequencing), to measure the genome-wide distribution of both exogenous and endogenous OGs with high specificity. Our data identified decreased OG occurrence at G-quadruplexes (G4s), in association with underrepresentation of OGs in promoters which have high GC content. Furthermore, we discovered that potential quadruplex sequences (PQSs) were hotspots of OGs, implying a role of non-G4-PQSs in OG-mediated oxidative stress response., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Radon inhalation decreases the level of lipid peroxide (LPO); this is attributed to the activation of antioxidative functions. This activation contributes to the beneficial effects of radon therapy, but there are no studies on the risks of radon therapy, such as DNA damage. We evaluated the effect of radon inhalation on DNA damage caused by oxidative stress and explored the underlying mechanisms. Mice were exposed to radon inhalation at concentrations of 2 or 20 kBq/m3 (for one, three, or 10 days). The 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels decreased in the brains of mice that inhaled 20 kBq/m3 radon for three days and in the kidneys of mice that inhaled 2 or 20 kBq/m3 radon for one, three or 10 days. The 8-OHdG levels in the small intestine decreased by approximately 20-40% (2 kBq/m3 for three days or 20 kBq/m3 for one, three or 10 days), but there were no significant differences in the 8-OHdG levels between mice that inhaled a sham treatment and those that inhaled radon. There was no significant change in the levels of 8-oxoguanine DNA glycosylase, which plays an important role in DNA repair. However, the level of Mn-superoxide dismutase (SOD) increased by 15-60% and 15-45% in the small intestine and kidney, respectively, following radon inhalation. These results suggest that Mn-SOD probably plays an important role in the inhibition of oxidative DNA damage., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Immunoassays have been extensively applied in the medical diagnostic field. Enzyme-Linked Immunosorbent Assay (ELISA) and Lateral Flow Immunochemical Assay (LFIA) are methods that have been well established to analysis of clinical substances such as protein, hormones, drugs, identification of antibodies and in the quantification of antigen. Over the past years, the application of these methods has been extended to assess the clinical oxidative stress condition based on monitoring of the 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) biomarker levels. The present manuscript provides an overview of the current immunoassays based on ELISA and LFIA technologies applied for a quantitative analysis of the 8-oxodG. The discussion focuses on the principles of development, improvement and analytical performance of these assays. The relationship of the molecule 8-oxodG as a clinical biomarker of the assessment of the oxidative stress condition is also discussed. Commercially available products to 8-oxodG analysis are also presented., (Copyright © 2021 Elsevier Inc. All rights reserved.)

To provide insights into the cause of e-cigarette (e-cig) associated lung injury, we examined the effects of propylene glycol (PG) and glycerol (G), two common solvent carriers used to deliver nicotine/flavor, on markers of oxidative stress and inflammation in female B6C3F1 mice which had been used successfully in tobacco smoke (TS)-induced lung carcinogenesis. Mice exposed to air and TS were used as negative and positive controls, respectively. Using LC-MS/MS, we showed that PG/G alone, in the absence of nicotine, significantly increased the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG or its tautomer 8-oxodG), a biomarker of DNA oxidative damage, in lung and plasma of mice; moreover, addition of nicotine (12 and 24 mg/mL) in e-cig liquid appears to suppress the levels of 8-oxodG. Exposure to e-cig aerosols or TS induced nonsignificant increases of plasma C-reactive protein (CRP), a biomarker of inflammation; nonetheless, the levels of fibronectin (FN), a biomarker of tissue injury, were significantly increased by e-cig aerosols or TS. Although preliminary, our data showed that exposure to e-cig aerosols induced a higher score of lung injury than did control air or TS exposure. Our results indicate that the B6C3F1 mouse model may be suitable for an in-depth examination of the impact of e-cig on lung injury associated with oxidative stress and inflammation and this study adds to the growing evidence that the use of e-cig can lead to lung damage.

Neonicotinoid insecticides (NEOs) are widely used around the world. The distribution of NEOs in paired saliva and periodontal blood samples was not previously documented in China. In this study, the concentrations of six NEOs and three corresponding metabolites were measured in 188 paired saliva and periodontal blood samples collected from South China. NEOs and their metabolites were frequently detected (68-94%) in paired saliva and periodontal blood, with median levels of 0.01-0.99 ng/mL. 1-Methyl-3-(tetrahydro-3-furylmethyl) urea was the most predominant NEO in paired saliva (39%) and periodontal blood (42%). Gender-related differences in NEOs and their metabolite concentrations were found: males showed lower levels than females. We calculated the concentration ratios between saliva and periodontal blood (S/PB ratios), and found that the median S/PB ratios of NEO and their metabolites were higher than 1, indicating that NEOs and their metabolites were easily excreted via saliva. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) was measured in paired saliva and periodontal blood as a marker of oxidative stress. 8-OHdG concentrations in saliva and periodontal blood were significantly and positively correlated (p < 0.05) with the concentrations of most NEOs and their metabolites in saliva and periodontal blood samples. These findings indicated that exposure to NEOs and their metabolites is associated with oxidative stress. This study is the first to report NEOs and their metabolites in paired saliva and periodontal blood samples collected from South China., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Oxidative DNA damage plays an important role in the pathogenesis of various diseases. Among oxidative DNA lesions, 8-oxoguanine (8-oxoG) and its corresponding nucleotide 8-oxo-2'-deoxyguanosine (8-oxodG), the guanine and deoxyguanosine oxidation products, have gained much attention, being considered biomarkers for oxidative DNA damage. Both 8-oxoG and 8-oxodG are used to predict overall body oxidative stress levels, to estimate the risk, to detect, and to make prognosis related to treatment of cancer, degenerative, and other age-related diseases. The need for rapid, easy, and low-cost detection and quantification of 8-oxoG and 8-oxodG biomarkers of oxidative DNA damage in complex samples, urine, blood, and tissue, caused an increasing interest on electrochemical sensors based on modified electrodes, due to their high sensitivity and selectivity, low-cost, and easy miniaturization and automation. This review aims to provide a comprehensive and exhaustive overview of the fundamental principles concerning the electrochemical determination of the biomarkers 8-oxoG and 8-oxodG using nanostructured materials (NsM), such as carbon nanotubes, carbon nanofibers, graphene-related materials, gold nanomaterials, metal nanoparticles, polymers, nanocomposites, dendrimers, antibodies and aptamers, and modified electrochemical sensors.

Background: Exposure to environmental chemicals may be a modifiable risk factor for progression of chronic kidney disease (CKD). The purpose of this study was to examine the impact of serially assessed exposure to bisphenol A (BPA) and phthalates on measures of kidney function, tubular injury, and oxidative stress over time in a cohort of children with CKD., Methods and Findings: Samples were collected between 2005 and 2015 from 618 children and adolescents enrolled in the Chronic Kidney Disease in Children study, an observational cohort study of pediatric CKD patients from the US and Canada. Most study participants were male (63.8%) and white (58.3%), and participants had a median age of 11.0 years (interquartile range 7.6 to 14.6) at the baseline visit. In urine samples collected serially over an average of 3.0 years (standard deviation [SD] 1.6), concentrations of BPA, phthalic acid (PA), and phthalate metabolites were measured as well as biomarkers of tubular injury (kidney injury molecule-1 [KIM-1] and neutrophil gelatinase-associated lipocalin [NGAL]) and oxidative stress (8-hydroxy-2'-deoxyguanosine [8-OHdG] and F2-isoprostane). Clinical renal function measures included estimated glomerular filtration rate (eGFR), proteinuria, and blood pressure. Linear mixed models were fit to estimate the associations between urinary concentrations of 6 chemical exposure measures (i.e., BPA, PA, and 4 phthalate metabolite groups) and clinical renal outcomes and urinary concentrations of KIM-1, NGAL, 8-OHdG, and F2-isoprostane controlling for sex, age, race/ethnicity, glomerular status, birth weight, premature birth, angiotensin-converting enzyme inhibitor use, angiotensin receptor blocker use, BMI z-score for age and sex, and urinary creatinine. Urinary concentrations of BPA, PA, and phthalate metabolites were positively associated with urinary KIM-1, NGAL, 8-OHdG, and F2-isoprostane levels over time. For example, a 1-SD increase in ∑di-n-octyl phthalate metabolites was associated with increases in NGAL (β = 0.13 [95% CI: 0.05, 0.21], p = 0.001), KIM-1 (β = 0.30 [95% CI: 0.21, 0.40], p < 0.001), 8-OHdG (β = 0.10 [95% CI: 0.06, 0.13], p < 0.001), and F2-isoprostane (β = 0.13 [95% CI: 0.01, 0.25], p = 0.04) over time. BPA and phthalate metabolites were not associated with eGFR, proteinuria, or blood pressure, but PA was associated with lower eGFR over time. For a 1-SD increase in ln-transformed PA, there was an average decrease in eGFR of 0.38 ml/min/1.73 m2 (95% CI: -0.75, -0.01; p = 0.04). Limitations of this study included utilization of spot urine samples for exposure assessment of non-persistent compounds and lack of specific information on potential sources of exposure., Conclusions: Although BPA and phthalate metabolites were not associated with clinical renal endpoints such as eGFR or proteinuria, there was a consistent pattern of increased tubular injury and oxidative stress over time, which have been shown to affect renal function in the long term. This raises concerns about the potential for clinically significant changes in renal function in relation to exposure to common environmental toxicants at current levels., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: HT reports NIDDK grants and consultancy agreements with Retrophin, Goldfinch Bio, Chemocentryx and Otsuka Pharmaceutical.

Introduction: copper dyshomeostasis has long been linked with several neurodegenerative disorders. The binding of Cu with amyloid beta and other neuronal proteins in the brain leads to the generation of oxidative stress, which eventually causes neurotoxicity., Method: the present study was aimed at elucidating the efficacy of monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA) and d-penicillamine (DPA) (0.3 mEq kg-1, oral administration for 2 weeks) against Cu(ii)-induced (20 mg kg-1, oral administration for 16 weeks) neurotoxicity in Sprague-Dawley (SD) rats., Results: we observed that the MiADMSA treatment modulated the altered oxidative and nitrosative stress parameters, antioxidant enzymes, and acetylcholinesterase (AChE) activity. Significant improvements were noticed in the neurobehavioral parameters except for the memory parameter. We also observed moderate improvement of memory impairment in the rats treated with MiADMSA and DPA post Cu(ii) exposure, as assessed by a passive avoidance test. Disease progression involves multiple factors and results in the up-regulation of intra and extracellular proteins such as amyloid beta and tau proteins; the expressions of these proteins were significantly reduced by the treatment proposed in our study, and these results were confirmed by ELISA and qRT-PCR. The expression of caspase-3 was higher in Cu(ii)-exposed rats, whereas it was lower in the MiADMSA-treated group. The proposed treatment reduced the copper-induced histological changes in the cortex and hippocampus regions of the brain., Conclusion: it can be summarised from the present study that MiADMSA is effective in reducing Cu(ii)-induced oxido-nitrosative stress, antioxidant defense enzymes, neurobehavioral changes, neuronal markers, apoptotic markers, and their genetic expressions. We conclude that chelation therapy using MiADMSA might be a promising approach for the treatment of copper-induced neurotoxicity.

Oxidative stress in the follicular fluid (FF) is thought to be responsible for the abnormal development of oocytes. In our study patients with polycystic ovarian syndrome (PCOS), endometriosis, and tubal infertility factor (TIF), and healthy women with a male factor of infertility, were prospectively enrolled. From each patient, a sample of individual FF was collected from a dominant follicle. Concentration levels of TAS, 8-IP, 8-OHdG, and AMH were determined. In women with PCOS, we found significantly lower values of oxidative stress markers in the FF. 8-IP and TAS levels were lower in the FF of women with endometriosis. In women with TIF, we also found significantly lower values of all tested markers in the FF, except for 8-OHdG and AMH. We wanted to see whether the biomarker measured in the FF in an individual diagnosis could predict a successfully obtained embryo from this particular follicle. The FF 8-OHdG result in PCOS patients stood out and proved to be a good predictive marker of matured and fertilized oocytes in these patients. Further research is needed to be able to apply the acquired knowledge in improving the outcome of IVF procedures.

Objective: Squamous Cell Carcinoma is almost always preceded by potentially malignant disorders in the oral cavity before malignant transformation. Characterization of  8-OHdG from the saliva offers a relatively non-invasive, simple and efficient methodology for monitoring oxidative stress in subjects of Premalignant oral disorders (PMOD) and Oral Squamous Cell Carcinoma (OSCC). Hence the aim of the current study is to estimate the levels of salivary 8-hydroxydeoxyguanosine (8-OHdG) as a potential DNA Damage Biomarker in OSMF and OSCC patients in comparison to healthy individuals to assess disease progression from potentially malignant oral disorder to frank malignancy., Materials and Methods: The study was conducted among 90 patients [Oral Squamous cell carcinoma (n=30) and Oral Submucous Fibrosis (n=30) and healthy gender and age matched controls (n=30)]. 4ml of unstimulated saliva was collected from each of the subjects and was subjected to Sandwich ELISA for the quantification of salivary 8-OHdG. Statistical analysis was done using ANOVA, and p value was set at ≤0.05., Results: The mean age of OSCC patients were 56.8±11.8 years. Smoking was the most prevalent adverse habit among this group (66.6%) followed by Smokeless tobacco chewers (40%). The mean age of OSMF patients was 46.2± 9.8 years. Smokeless tobacco was the most predominant habit among the OSMF patients (83.33%) followed by smoking (33.33%). The mean OHdG levels among the controls was 6.59±1.47 (ng/dl) and almost doubled in patients of OSMF 13.89±1.96(ng/dL) and further raised in OSCC patients 19.96 ± 2.11 (ng/dL). These levels showed a highly significant difference (p <0.0001) in mean on comparison by using one-way ANOVA. Pearson correlation between the groups were also statistically significant (p=0.000)., Conclusion: There were significant differences in the concentration of salivary 8-OHdG between healthy controls, OSMF, and OSCC patients. Hence, 8-OHdG can be used as a novel biomarker of DNA damage to assess disease progression.

Background: The profile of sirtuin 3 (SIRT3), 8-hydroxy-2'-deoxyguanosine (8-OHdG), brain-derived neurotrophic factor (BDNF) and serotonin (5-HT) in cord blood and in early breast milk was studied and it was related to perinatal factors. 5-HT and BDNF signalling systems have been claimed to play a critical role in intrauterine development, postnatal adaptation and lactation. Since prematurity and Caesarean birth are frequently associated with inflammation and related oxidative stress, an attempt was made to reveal the adaptive changes of the protective SIRT3 and the complex interplay among these bioactive components in cord blood and early breast milk., Methods: Three groups each consisting of 30 mothers were included in the study: mothers who underwent spontaneous vaginal birth at term (group I), Caesarean section at term (group II) and preterm birth (group III). Venous cord blood and early breast milk samples were collected for measuring the biomarkers. SIRT3, 8-OHdG, BDNF and 5-HT levels were determined by using commercially available ELISA kits., Results: It was demonstrated that cord blood levels of SIRT3, BDNF and 5-HT were markedly reduced whereas those of 8-OHdG were significantly elevated after preterm birth when compared with birth at term. The Caesarean section was associated with a moderate decrease in BDNF and 5-HT, however, both SIRT3 and 8-OHdG remained unaffected. Breast milk levels of all biomarkers studied proved to be independent of their corresponding cord blood concentrations. In response to preterm birth breast milk SIRT3, 8-OHdG and 5-HT increased significantly, while a drastic fall occurred in BDNF. A significant positive relationship was found of 5-HT with SIRT3 and 8-OHdG irrespective of the gestational age and the mode of delivery., Conclusions: It is suggested that the selected biomarkers in the breast milk mostly derive from local production by the mammary glands and 5-HT may have an essential role in the control of this process.

A sensitive and enzyme-free electrochemical aptasensor was constructed for the sensing of 8-hydroxy-2'-deoxyguanosine (8-OH-dG). In the process of constructing the aptasensor, triple signal amplification strategies were introduced to enhance the sensitivity. First, every aptamer/pDNA complex immobilized on magnetic beads could release three kinds of pDNAs when 8-OH-dG was introduced, which caused three-fold magnification of the target. Second, the released three kinds of pDNAs initiated catalyzed hairpin assembly between two hairpin DNAs (HP1 and HP2) on a gold electrode. Meanwhile, the three kinds of pDNAs were released again by a strand displacement reaction to obtain the next catalyzed hairpin assembly. Third, the emerging toehold of HP2 further induced a hybridization chain reaction (HCR) between two hairpin DNAs (HP3 and HP4), forming a long double-stranded DNA concatemer on the surface of the electrode. Finally, [Ru(NH 3 ) 6 ] 3+ , an electroactive cation, was adsorbed onto the long dsDNA concatemer by electrostatic interactions and consequently, an electrochemical signal was generated. Under this triple signal amplification, a low detection limit down to 24.34 fM has been obtained for 8-OH-dG determination, which is superior to those of most previously reported methods.

Recently the connection between oxidative stress and various diseases, including cancer and Alzheimer's, attracts notice as a pathway suitable for diagnostic purposes. 8-Oxo-deoxyguanosine and 8-oxo-deoxyadenosine produced from the interaction of reactive oxygen species with DNA become prominent as biomarkers. Several methods have been developed for their determination in biofluids, including solid-phase extraction and enzyme-linked immunosorbent assays. However, still, there is a need for reliable and fast analytical methods. In this context, solid-phase microextraction offers many advantages such as flexibility in geometry and applicable sample volume, as well as high adaptability to high-throughput sampling. In this study, a solid-phase microextraction method was developed for the determination of 8-oxo-deoxyguanosine and 8-oxo-deoxyadenosine in biofluids. The extractive phase of solid-phase microextraction consisted of hydrophilic-lipophilic balanced polymeric particles. In order to develop a solid-phase microextraction method suitable for the determination of the analytes in saliva and urine, several parameters, including desorption solvent, desorption time, sample pH, and ionic strength, were scrutinized. Analytical figures of merit indicated that the developed method provides reasonable interday and intraday precisions (<15% in both biofluids) with acceptable accuracy. The method provides a limit of quantification for both biomarkers at 5.0 and 10.0 ng/mL levels in saliva and urine matrices, respectively., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In this work, the reusable high-efficiency cascade amplification of nanozymes was obtained for sensitive electrochemical analysis of target 8-hydroxy-2'-deoxyguanosine (8-OHdG) based on reversible capture/release of electronic media in a fast and green manner.

Oxidative stress plays a crucial role in the development of diseases induced by welding fumes. To our knowledge, little information is available on the relationship between multiple heavy metal exposure and oxidative stress in welders. We assessed the relationship between multiple heavy metal exposure and oxidative damage by analyzing 174 nonsmoking male welders in a shipyard. Urinary metals were used as the internal dose of exposure to metals in welding fumes, and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) was used as an oxidative DNA damage marker. The relationship between workers' metal levels and 8-OHdG was estimated using a multiple linear regression model. The geometric mean levels of urinary chromium (Cr), nickel (Ni), cadmium (Cd), and lead (Pb) were considerably higher in welders than in controls. Urinary Cr and Ni were determined as effective predictors of urinary 8-OHdG levels after adjusting for covariates. Oxidative DNA damage was associated with both Cr and Ni of welding fume exposure in shipyard welders (Ln Cr: β = 0.33, 95%C.I. = 0.16-0.49; Ln Ni: β = 0.27, 95%C.I. = 0.12-0.43). In this study, we investigated the significantly positive relationship between urinary metals (especially Cr and Ni) and 8-OHdG in nonsmoking shipyard welders. Moreover, the use of particulate respirators did not reduce metal exposure and oxidative damage. Therefore, we infer that hazard identification for welders should be conducted., Competing Interests: The authors declare no conflict of interest.

The present research was designed to evaluate the protective effects and underlying mechanisms of propionate, a bioactive food additive, on mitochondrial disruption, neuron necrosis and neurological deficits after epilepsy seizures. Epilepsy seizures was induced by repetitive injections of pentylenetetrazol at a dose of 37 mg per kg. Propionate (37.5, 50 and 75 mg/kg) as well as sodium valproate (300 mg/kg) were administrated intragastrically (i.g.) 1 h before each PTZ injection and continued for 40 days. The influence of propionate was assessed by many biochemical assays and neurobehavioral experiments. The results of gas chromatography (GC) analysis indicated that increased concentration of propionate can be explored in hippocampus area of propionate + PTZ treated animals. Propionate decreased epilepsy seizure intensity, increased latency of seizures. Meanwhile, propionate treatment reversed the structure disruption of the mitochondria, improved ATP level and lessened 8-OHdG level in the brains of animals with seizures. In addition, we find propionate pretreated can increase activities of the antioxidant enzymes (CAT, SOD, as well as GSH-Px) in mitochondria. Additionally, propionate reduced neuronal loss in hippocampus and our results suggest that HIF-1α/ERK pathway and neuron necrosis exists potential linkage during epileptogenesis. Moreover, as a result, propionate administration can significantly improve the neurological function estimated by a battery of functional tests. In conclusion, treatment with propionate attenuates mitochondrial disruption, hippocampal apoptosis and neurological deficits in a mouse model of epilepsy seizures. Therefore, propionate, currently used as a food preservative, has a potential additional advantage of ameliorating epilepsy seizures., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A detection and degradation platform was developed to optically quantify the 6-enolate, 8-keto-dG, an important tautomer of mitochondrial mutated DNA 8-oxo-dG. We first found that 6-enolate, 8-keto-dG offers particular fluorescence emission under the conditions between pH ∼ 7 and ∼11. Thus, a mitochondria-targeting photosensitizer NV-12P was prepared to offer simultaneously photoinduced electron transfer and fluorescence resonance energy transfer (FRET) with 6-enolate, 8-keto-dG. Furthermore, NV-12P can also generate a reactive oxygen species to degrade 6-enolate, 8-keto-dG under irradiation conditions. This is the first publication about optical characterization, concentration detection and photodegradation of 6-enolate, 8-keto-dG, either in biological or in vitro applications.

Our aim was to optimize 8-hydroxy-2'-deoxyguanosine (8-OHdG) immunodetection in order to detect DNA damage caused by oxidative stress that may not be detected by other DNA integrity analysis techniques, especially due to the high compaction of DNA in ruminants. Semen samples from 6 rams were cryopreserved. After thawing, samples were subjected to the DNA oxidation quantification using an 8-OHdG immunodetection assay by flow cytometry. We have evaluated two different incubation times (30 min vs. overnight) at 4°C of the primary antibody (monoclonal anti-8-OHdG antibody). We have also compared the results of this technique with the sperm chromatin structure assay (SCSA ® ). The analysis revealed that there were no significant differences (p > .05) between different incubation times. However, overnight incubation seems to cause more non-specific binding of the secondary antibody. Significant differences (p < .05) between subjects and oxidation controls (8 M H 2 O 2 /800 μM FeSO 4 •7H 2 O) were evident. We can conclude that the 8-OHdG immunodetection assay for DNA oxidation quantification of ram sperm can be performed subjecting sperm samples to a very high oxidative treatment., (© 2019 Blackwell Verlag GmbH.)

The enzyme-modified comet assay is a commonly used method to detect specific DNA lesions. However, still a lot of errors are made by many users, leading to dubious results and even misinterpretations. This technical note describes some critical points in the use of the enzyme-modified comet assay, such as the enzyme concentration, the time of incubation, the format used and the equipment. To illustrate the importance of these conditions/parameters, titration experiments of formamidopyrimidine DNA glycosylase (Fpg) were performed using the 2 gels/slide and the 12 minigels/slide formats (plus the 12-Gel Comet Assay Unit™). Incubation times of 15 and 30 min, and 1 h were used. Results showed that the 12 minigels/slide system requires a lower volume and concentration of Fpg. A longer time of incubation has a bigger impact when using such format. Moreover, the paper describes how to perform and interpret a titration experiment when using the enzyme-modified comet assay., (Copyright © 2018 Elsevier B.V. All rights reserved.)

TiO 2 particles are widely used in products for everyday consumption, such as cosmetics and food; their possible adverse effects on human health must therefore be investigated. The aim of this study was to document in vitro impact of the food additive E171, i.e. TiO 2 , and of TiO 2 nanoparticles, on a co-culture of Caco-2 and HT29-MTX cells, which is an in vitro model for human intestine. Cells were exposed to TiO 2 particles three days after seeding, i.e. while they were not fully differentiated. Cell viability, reactive oxygen species (ROS) levels and DNA integrity were assessed, by MTT assay, DCFH-DA assay, alkaline and Fpg-modified comet assay and 8-oxo-dGuo measurement by HPLC-MS/MS. The mRNA expression of genes involved in ROS regulation, DNA repair via base-excision repair, and endoplasmic reticulum stress was assessed by RT-qPCR. Exposure to TiO 2 particles resulted in increased intracellular ROS levels, but did not impair cell viability and did not cause any oxidative damage to DNA. Only minor changes in mRNA expression were detected. Altogether, this shows that E171 food additive and TiO 2 nanoparticles only produce minor effects to this in vitro intestinal cell model., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Autophagy is a catabolic process that involves the degradation of cellular components through the lysosomal machinery, relocating nutrients from unnecessary processes to more pivotal processes required for survival. It has been reported that systemic disruption of the Atg5 or Atg7 gene, a component of autophagy, is lethal and that its tissue-specific disruption causes tissue degeneration in several organs. However, the functional significance of autophagy in the thyroid glands remains unknown. Our preliminary data imply the possible involvement of dysfunctional autophagy in radiation-induced thyroid carcinogenesis. Therefore, we evaluated the effect of Atg5 gene knockout (KO) on thyroid morphology and function. To this end, Atg5flox/flox mice were crossed with TPO-Cre mice, yielding the thyroid follicular epithelial cell (thyrocyte)‒specific ATG5-deficient mice (Atg5thyr-KO/KO). Atg5 gene KO was confirmed by a lack of ATG5 expression, and disruption of autophagy was demonstrated by a decrease in microtubule-associated protein 1 light chain 3-II puncta and an increase in p62. Atg5thyr-KO/KO mice were born normally, and thyroid morphology, thyroid weights, and serum T4 and TSH levels were almost normal at 4 months. However, at 8 and 12 months, a decrease in the number of thyrocytes and an increase in TUNEL+-thyrocytes were observed in Atg5thyr-KO/KO mice even though thyroid function was still normal. The number of irregularly shaped (gourd-shaped) follicles was also increased. Excess oxidative stress was indicated by increased 8-hydroxy-2'-deoxyguanosine and 53BP1 foci in Atg5thyr-KO/KO mice. These data demonstrate that thyrocytes gradually undergo degradation/cell death in the absence of basal levels of autophagy, indicating that autophagy is critical for the quality control of thyrocytes., (Copyright © 2019 Endocrine Society.)

Heart failure (HF) has become a global public health problem due to its unclear pathogenesis. Our previous studies have found that RNA oxidation is associated with the occurrence and development of a variety of chronic diseases in the elderly, but whether RNA oxidation is related to the pathogenesis of HF remains unclear. Male Dahl salt-sensitive rats (DSSR) were divided into 8% NaCl groups and 0.3% NaCl groups. The blood pressure of DSSR, HE staining of cardiac tissue, cardiac function index of colour Doppler echocardiography and plasma N-terminal probrain Natriuretic Peptide (NT-ProBNP) were used to evaluate the model making. The levels of 8-hydroxyguanosine (8-oxoGsn) and 8-hydroxydeoxyguanosine (8-oxodGsn) in myocardium and urine of DSSR were determined by high-performance liquid chromatography-mass spectrometry (LC-MS/MS). The expression of ERK-MAPK pathway and MTH1 was detected by Western blot (WB). Rats in the 8% NaCl group developed heart failure symptoms such as increased blood pressure, myocardial hypertrophy, decreased diastolic function, and increased plasma NT-ProBNP. The content of 8-oxoGsn in urine and heart tissue also increased, which was positively correlated with the related indicators of heart failure. This process is also accompanied by the sequential activation of ERK-MAPK pathway molecules and the increase of MTH1. The mechanism of RNA oxidation and inhibition is related to the occurrence and development of HF, which may be involved through ERK-MAPK pathway.

Telomeres are capped at the end of the chromosome and gradually shorten when the cell divides. When there is an oxidative stress, it can cause the DNA to be damaged. Hence, 8-hydroxy-2'-deoxyguanosine (8-OHdG) has been shown to be an indicator for oxidative DNA damage. This study aimed to determine the relative telomere length (RTL) and 8-OHdG levels in neoplastic tissues, adjacent non-neoplastic tissues, and blood leukocytes of musculoskeletal (MS) tumor patients. Neoplastic tissues were compared to adjacent non-neoplastic tissues in MS tumor patients (n = 46). Peripheral blood leukocytes (PBLs) of MS tumor subjects were compared to those of age-matched healthy controls (n = 107). RTL was evaluated by quantitative real-time polymerase chain reaction and 8-OHdG levels were quantified by enzyme-linked immunosorbent assay. The RTL in neoplastic tissues was significantly shorter than that in non-neoplastic tissues [1.12 (0.86-1.46) vs 1.45 (1.25-1.65), P = 0.001]. PBLs had lower RTL than non-neoplastic tissues in MS tumor patients [1.04 (0.85-1.13) vs 1.45 (1.25-1.65), P < 0.001]. However, there was no significant difference between RTL in PBLs and in neoplastic tissues. In addition, PBLs of MS tumor patients had higher RTL than those of the controls [1.04 (0.85-1.13) versus 0.78 (0.68-0.90), P < 0.001]. The 8-OHdG levels in neoplastic tissues were remarkably higher than those in non-neoplastic tissues [8.14 (6.81-11.37) nM/μg/μl vs. 3.79 (2.53-6.17) nM/μg/μl, P < 0.001]. Furthermore, plasma 8-OHdG levels in MS tumor patients were markedly greater than those in the controls [102.50 (73.16-133.50) nM vs. 41.09 (6.81-11.37) nM, P < 0.001]. Area under the curve (AUC) was 0.7536 (95% confident interval (CI) 0.6602-0.8469) when the cut-off value of RTL in PBLs was 0.97. Also, plasma 8-OHdG levels depicted that when the cut-off value was 38.67 nM, the AUC was 0.7723 (95% CI 0.6920-0.8527). Moreover, ROC curve analysis showed that both RTL and 8-OHdG appeared to improve the sensitivity (85.68%) and specificity (70.91%) with the AUC 0.8639 (95% CI 0.7500-0.9500). This study suggested that blood leukocyte RTL and plasma 8-OHdG could serve as promising non-invasive biomarkers to differentiate between MS tumor patients and healthy controls. Additionally, telomere attrition and increased oxidative DNA damage might play contributory roles in the pathogenesis of MS tumors.

The present study aimed to compare the effect of carvacrol essential oil and carvacrol nanoemulsion against experimental Alzheimer's (AD). Forty male albino rats were used and divided into four groups as follow: control, AlCl 3 induced AD, carvacrol oil treated and carvacrol nanoemulsion treated groups. Brain nor-epinephrine, serotonin and dopamine were analyzed by high performance liquid chromatography (HPLC). Levels of brain Thiobarbituric acid-reactive substances (TBARS), Superoxide dismutase (SOD), reduced glutathione (GSH), cholinesterase, and advanced oxidation protein product (AOPP) were evaluated. Urinary 8-hydroxyguanosine (8-OHdG) level was evaluated by HPLC. Brain Cyclooxygenase 1 and 2 (COX 1and 2) were analyzed by immunohistochemistry. AD induced by AlCl 3 in rats was depicted by the significant increase in the neurotransmitters levels which is accompanied with high degree of oxidative stress that was revealed in the elevated level of urinary 8-OHdG along with significant elevation in AOPP, TBARS, and cholinesterase levels and a significant decrease in SOD and GSH; these results are confirmed by immunohistochemistry analysis of COX 1 and 2. On the other hand, the treatment with carvacrol oil and carvacrol nanoemulsion were capable of mitigate effects mediated by AlCl 3 administration in treated rats. While the treatment with both approached succeeded to retract the negative impact of AlCl 3 ; but the effect of carvacrol nanoemulsion was more notable than the essential oil. Carvacrol oil and carvacrol nanoemulsion were eminent to overturn AlCl 3 induced brain AD which could be imputed to antioxidant and anti-inflammatory capabilities of carvacrol to alter oxidative stress effect. In extension; carvacrol nanoemulsion were evident to give more effective and efficient way in carvacrol delivery to pass through blood brain barriers and ameliorate brain changes.

The present study focuses on the investigation of the oxidized cell-free DNA (cfDNA) properties in several experimental models, including cultured cerebellum cells, peripheral blood lymphocytes (PBL), plasma, and hippocampus under an acute and chronic unpredictable stress model in rats. Firstly, our study shows that Spectrum Green fluorescence-labeled oxidized cfDNA fragments were transferred into the cytoplasm of 80% of the cerebellum culture cells; meanwhile, the nonoxidized cfDNA fragments do not pass into the cells. Oxidized cfDNA stimulates the antioxidant mechanisms and induction of transcription factor NRF2 expression, followed by an activation of NRF2 signaling pathway genes-rise of Nrf2 and Hmox1 gene expression and consequently NRF2 protein synthesis. Secondly, we showed that stress increases plasma cfDNA concentration in rats corresponding with the duration of the stress exposure. At the same time, our study did not reveal any significant changes of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) level in PBL of rats under acute or chronic stress, probably due to the significantly increased Nrf2 expression, that we found in such conditions. 8-oxodG is one of the most reliable markers of DNA oxidation. We also found an increased level of 8-oxodG in the hippocampal homogenates and hippocampal dentate gyrus in rats subjected to acute and chronic stress. Taken together, our data shows that oxidized cfDNA may play a significant role in systemic and neuronal physiological mechanisms of stress and adaptation.

A method is described for the fluorometric determination of DNA containing oxidatively damaged product 8-hydroxy-2'-deoxyguanosine (DNA-8-OHdG). Carbon dots (CDs) were modified with glutaraldehyde for DNA conjugation, and antibody against 8-OHdG was immobilized on gold nanoparticles (AuNPs). The presence of DNA-8-OHdG can be linked to CDs by reaction of amino groups on DNA with glutaraldehyde. AuNPs were brought closely to CDs by specific immune reaction between 8-OHdG and antibody on AuNPs. Under 350 nm photoexcitation, the emission of CDs with a peak at 440 nm is quenched by the AuNPs and not restored. In the presence of DNA-8-OHdG, the measured fluorescence intensity decreases and quenching efficiency increases. The limit of detection is 700 pM, and the assay works in the 0.01 nM to 25 μM DNA-8-OHdG concentration range. The method is perceived to possess a good potential as a tool for detecting biomarkers for DNA damage due to oxidative stress. Graphical abstract A fluorometric immunoassay for detecting 8-hydroxy-2'-deoxyguanosine (8-OHdG) in oxidatively damaged DNA is reported. It is based on the use of carbon dots (CDs) and gold nanoparticles (AuNPs). Black wavy lines represent DNA. Yellow polygonal sharps represent 8-OHdG. Blue and pink balls represent CDs and AuNPs, respectively.

Background: In menopause, there is greater cellular exposure to oxidative stress, related to the decreased antioxidative effects of estrogen. These metabolic changes favor the progression of cardiovascular diseases, such as atherosclerosis. Abnormal function of the aorta - the most important artery - is associated with many cardiovascular diseases. Collagen, especially types I and III, is one of the most important aortic wall components and it can be affected by many factors, including menopause. The 8-OHdG is one of the main markers of DNA oxidative damage induced by reactive oxygen species (ROS)., Objective: We aimed to investigate effects of moderate aerobic training on the ascending aorta of LDL-knockout (LDL-KO) and ovariectomized female mice., Methods: A total of 15 C57BL/6 mice and 15 LDL-KO mice were divided into experimental groups. The thickness and volume density of types I and III collagen fibers were performed by morphoquantitative analysis, whereas the MMP-2 and MMP-9 and 8-OHdG were detected by immunohistochemistry and apoptosis was detected by the TUNEL assay. The significance level for all tests was p < 0.05., Results: Exercise causes an increase in the thickness of the aorta in LDL-KO groups, particularly accentuated in the ovariectomized groups. The type I collagen fibers showed an increase in volume density influenced by training in both Control groups and in the LDL-KO group. Type III collagen density decreased in both groups. The MMP-2 showed moderade immunostaining in the tunica media in LDL-KO groups, which did not occur in the control groups and the MMP-9 stained irregularly in all tissues. The marker 8-OhdG was stronger in the exercise training groups. Additionally, the ovariectomy, the exercise training and the LDL-KO treatments increased apoptosis., Conclusion: These results suggest that moderate-intensity aerobic exercise in ovariectomized mice associated to an increase in LDL rate possibly increases oxidative stress and apoptosis induction.

We used a novel automated sleep disruption (SD) apparatus to determine the impact of SD on sleep and molecular markers of oxidative stress in parvalbumin (PV) neurons in the rat prefrontal cortex (PFC). Rats were subjected to two 6 hr SD sessions from zeitgeber time (ZT) 0 to ZT6, one by the gentle handling method and the other by an automated agitator running the length of the rat's home cage floor (a novel SD method). The same rats were later subjected to a 12 hr SD session from ZT0 to ZT12. Sleep was disrupted with both methods, although rats slept less during gentle handling than during the automated condition. Immediately after both SD sessions, rats displayed compensatory sleep characterized by elevated slow-wave activity. We measured in the prelimbic prefrontal cortex (prelimbic PFC; 6 and 12 hr SD) and orbital frontal cortex (12 hr SD) the intensity of the oxidative stress marker, 8-oxo-2'-deoxyguanosine (8-oxo-dG) as well as the staining intensity of PV and the PV cell-associated perineuronal net marker, Wisteria floribunda agglutinin (WFA). In the prelimbic PFC, 6 hr SD increased the intensity of 8-oxo-dG, PV, and WFA. After 12 hr SD, the intensity of 8-oxo-dG was elevated in all neurons. PV intensity was elevated only in neurons colabeled with 8-oxo-dG or WFA, and no changes were found in WFA intensity. We conclude that in association with SD-induced sleep drive, PV neurons in the prelimbic PFC exhibit oxidative stress.