Ascorbic acid is essential for human health. As this vitamin is water-soluble, it cannot be stored in the body for a long time and is easily excreted in urine; therefore, it is necessary to ingest it in sufficient amounts every day. The fact that apples retain ascorbic acid in human bodies are known; however, this has not been experimentally demonstrated/documented. In this study, to clarify the effect of apple juice ingestion on the urinary excretion of ascorbic acid, we compared urinary ascorbic acid excretion in healthy women administered ascorbic acid alone or with apple juice. The experimental design was an unblinded randomized crossover study. Subjects ingested ascorbic acid in apple juice or ascorbic acid with water. Urine was collected after ingestion, and urinary ascorbic acid was measured. When ascorbic acid was ingested with apple juice, urinary excretion of ascorbic acid was significantly suppressed compared to when ascorbic acid was ingested alone. This suggests that apple juice intake can help retain ascorbic acid in the body.

Arsenic-related oxidative stress and resultant diseases have attracted global concern, while longitudinal studies are scarce. To assess the relationship between arsenic exposure and systemic oxidative damage, we performed two repeated measures among 5236 observations (4067 participants) in the Wuhan-Zhuhai cohort at the baseline and follow-up after 3 years. Urinary total arsenic, biomarkers of DNA oxidative damage (8-hydroxy-2\'-deoxyguanosine (8-OHdG)), lipid peroxidation (8-isoprostaglandin F2alpha (8-isoPGF2α)), and protein oxidative damage (protein carbonyls (PCO)) were detected for all observations. Here we used linear mixed models to estimate the cross-sectional and longitudinal associations between arsenic exposure and oxidative damage. Exposure-response curves were constructed by utilizing the generalized additive mixed models with thin plate regressions. After adjusting for potential confounders, arsenic level was significantly and positively related to the levels of global oxidative damage and their annual increased rates in dose-response manners. In cross-sectional analyses, each 1% increase in arsenic level was associated with a 0.406% (95% confidence interval (CI): 0.379% to 0.433%), 0.360% (0.301% to 0.420%), and 0.079% (0.055% to 0.103%) increase in 8-isoPGF2α, 8-OHdG, and PCO, respectively. More importantly, arsenic was further found to be associated with increased annual change rates of 8-isoPGF2α (β: 0.147; 95% CI: 0.130 to 0.164), 8-OHdG (0.155; 0.118 to 0.192), and PCO (0.050; 0.035 to 0.064) in the longitudinal analyses. Our study suggested that arsenic exposure was not only positively related with global oxidative damage to lipid, DNA, and protein in cross-sectional analyses, but also associated with annual increased rates of these biomarkers in dose-dependent manners.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals linked to adverse pregnancy outcomes. Although their underlying biological mechanisms are not fully understood, evidence suggests PFAS may disrupt endocrine functions and contribute to oxidative stress (OS) and inflammation.
OBJECTIVE: We examined associations between early pregnancy PFAS exposure and OS biomarkers, exploring potential effect modifications by fetal sex and maternal race.
METHODS: We used data from 469 LIFECODES participants with measured plasma PFAS (median 10 weeks gestation) and repeated measures (median 10, 18, 26, and 35 weeks gestation) of urinary OS biomarkers [8-iso-prostaglandin-F2α (8-isoprostane) and 8-hydroxydeoxyguanosine (8-OHdG)]. Protein damage biomarkers (chlorotyrosine, dityrosine, and nitrotyrosine) were additionally measured in plasma from a subset (N = 167) during the third visit. Associations between each PFAS and OS biomarkers were examined using linear mixed-effects models and multivariable linear regressions, adjusting for potential confounders, including maternal age, race, education level, pre-pregnancy BMI, insurance status, and parity. Effect modifications were evaluated by including an interaction term between each PFAS and fetal sex or maternal race in the models.
RESULTS: We observed significant positive associations between PFOS and 8-isoprostane, with a 9.68% increase in 8-isoprostane levels (95% CI: 0.10%, 20.18%) per interquartile range increase in PFOS. In contrast, PFUA was negatively associated [9.32% (95% CI: -17.68%, -0.11%)], while there were suggestive positive associations for MPAH and PFOA with 8-isoprostane. The associations of several PFAS with 8-OHdG varied by fetal sex, showing generally positive trends in women who delivered females, but negative or null in those who delivered males. No significant effect modification by maternal race was observed.
CONCLUSIONS: This study provides evidence linking PFAS exposure to OS during pregnancy, with potential sex-specific effects of certain PFAS on 8-OHdG. Further research should explore additional OS/inflammatory biomarkers and assess the modifying effects of dietary and behavioral patterns across diverse populations.

Oxidative stress (OS) has been linked to cell damage and chronic disease development; however, the study of psychological factors related with OS has been limited, as has its relationship with biochemical and personal variables. Therefore, the aim of this study was to evaluate the association between a wide variety of personal, psychological, and biochemical factors with OS in a sample of healthy Mexican people. A total of 134 participants, from which 70 (52%) were women, without known chronic conditions were included in the study, and the molecule 8-hydroxy-2\'-deoxyguanosine (8-OHdG) was also measured as a marker of OS. We observed in the multivariate analysis of the whole sample that depressive symptoms (measured with CES-D scale) were the only psychological variable significantly associated (positively) with 8-OHdG. In addition, the following sociodemographic variables were associated with 8-OHdG: age, schooling (positively correlated), and the frequency of vitamins/antioxidant consumption (negatively correlated). The biochemical variables of erythrocytes in urine and amylase were positively correlated with 8-OHdG, while glucose was negatively correlated with it. Additional biochemical variables were associated in the multivariate analysis of each sex, including the positive correlation of LDL-cholesterol, LDH enzyme, lymphocytes, and the negative correlation of phosphorus and eosinophils in women\'s samples, as well as the positive correlation of potassium, uric acid, and leucocytes in urine and the negative correlation of erythrocytes and lipase in the men\'s samples. In conclusion, depression was the only psychological variable positively correlated with 8-OHdG after adjusting for confounders, and new associations with biochemical variables were found with some differences between sexes.

Oxidative stress is an important toxicity and genotoxicity mechanism of many chronic adverse health outcomes. This study developed a sensitive extraction method for urine matrix (based on lyophilization, without the need for pre-cleaning by solid phase extraction), coupled to LC-MS/MS analysis of the biomarker 8-hydroxy-2\'-deoxyguanosine (8-OHdG). The methodology was validated in urine samples from a cohort of Spanish pregnant women collected during the first, second and third trimester of pregnancy, and urine samples collected within 24 h after delivery (n = 85). A detection and quantification limit of 0.01 and 0.05 μg/L, respectively, were established. The median 8-OHdG concentration was 2.18 μg/L (range 0.33-7.79); and the corresponding creatinine-adjusted concentrations ranged from 1.04 to 13.12 with median of 4.48 μg 8-OHdG/g creatinine. The concentrations of non-adjusted 8-OHdG significantly decreased (p < 0.05) in the 3rd trimester and post-delivery urine samples when compared to the 1st trimester levels. 8-OHdG concentrations were further studied in placenta samples matching the same urine samples (n = 26), with a median value of 1.3 ng 8-OHdG/g of tissue. Placental 8-OHdG concentrations were correlated with urinary levels of non-adjusted 8-OHdG in the 3rd trimester. Considering the small cohort size, results must be interpreted with caution, however statistical analyses revealed elevated urinary non-adjusted 8-OHdG levels in the 1st trimester of mothers that delivered boys compared to those who delivered girls (p < 0.01). Increased urinary non-adjusted 8-OHdG concentrations at the time of delivery were significantly associated with clinical records (any type of clinical record during pregnancy; p < 0.05). The novel extraction and analytical method for the assessment of 8-OHdG is applicable for sensitive analysis of multiple analytes or biomarkers in urine matrix. This method could also be applied for other matrices such as blood or tissues. Our findings show that 8-OHdG in urine of pregnant women could predict oxidative stress in placenta and can be related to characteristics such as maternal obesity, mode of delivery and newborn sex.

A study was conducted within the European Human Biomonitoring Initiative (HBM4EU) to characterize occupational exposure to Cr(VI). Herein we present the results of biomarkers of genotoxicity and oxidative stress, including micronucleus analysis in lymphocytes and reticulocytes, the comet assay in whole blood, and malondialdehyde and 8-oxo-2′-deoxyguanosine in urine. Workers from several Cr(VI)-related industrial activities and controls from industrial (within company) and non-industrial (outwith company) environments were included. The significantly increased genotoxicity (p = 0.03 for MN in lymphocytes and reticulocytes; p < 0.001 for comet assay data) and oxidative stress levels (p = 0.007 and p < 0.001 for MDA and 8-OHdG levels in pre-shift urine samples, respectively) that were detected in the exposed workers over the outwith company controls suggest that Cr(VI) exposure might still represent a health risk, particularly, for chrome painters and electrolytic bath platers, despite the low Cr exposure. The within-company controls displayed DNA and chromosomal damage levels that were comparable to those of the exposed group, highlighting the relevance of considering all industry workers as potentially exposed. The use of effect biomarkers proved their capacity to detect the early biological effects from low Cr(VI) exposure, and to contribute to identifying subgroups that are at higher risk. Overall, this study reinforces the need for further re-evaluation of the occupational exposure limit and better application of protection measures. However, it also raised some additional questions and unexplained inconsistencies that need follow-up studies to be clarified.

UNASSIGNED: The literature suggests that stress may play a pivotal role in the precipitation of acute central serous chorioretinopathy (CSC) because chorioretinal integrity can be affected by the psychosocial state of the patient, indicating the need for a biomarker. Not only physical stress but also psychological stress causes many types of physical disorders. However, little is known about the pathophysiology of stress-induced disease. The objective of this study was to investigate whether serum factors might be involved in the development of stress-induced ocular diseases.
UNASSIGNED: This observational case series included 33 eyes of 33 consecutive patients with treatment-naïve acute CSC. Fifty eyes of 50 age-matched healthy volunteers were included in this study as non-CSC controls. Serum samples were collected from all participants, and the levels of mitochondrial DNA (mtDNA) were measured by quantitative real-time (RT)-PCR. Serum levels of high-mobility group box (HMGB) 1 and 8-hydroxy-2\'-deoxyguanosine (8-OHdG), biological markers of acute/chronic inflammation and oxidative stress, were also measured. The relationships between serum mtDNA, 8-OHdG, and HMGB1 concentrations were investigated by multivariate regression analysis, alongside an assessment of clinical data.
UNASSIGNED: In the treatment-naïve acute CSC group, the serum mtDNA levels (36.5 ± 32.4 ng/mL) were significantly higher than the levels in the control group (7.4 ± 5.9 ng/mL; p < 0.001). Serum levels of 8-OHdG and HMGB1 in treatment-naïve acute CSC patients measured 0.12 ± 0.08 ng/mL and 18.1 ± 35.0 ng/mL, respectively, indicating that HMGB1 levels were elevated in CSC compared with the control group. Multivariable regression analysis demonstrated that increased serum mtDNA levels were significantly associated with the height of serous retinal detachment.
UNASSIGNED: We showed serum mtDNA and HMGB1 level elevation and its relation to the clinical activities of CSC, indicating that serum mtDNA and HMGB1 could serve as biomarkers for the acute phase of the disease. The use of these biomarkers makes it possible to predict disease onset and determine disease severity.

Complications in type 2 diabetes (T2D) arise from hyperglycemia-induced oxidative stress. Here, we examined the effectiveness of supplementation with the endogenous antioxidant glutathione (GSH) during anti-diabetic treatment. A total of 104 non-diabetic and 250 diabetic individuals on anti-diabetic therapy, of either sex and aged between 30 and 78 years, were recruited. A total of 125 diabetic patients were additionally given 500 mg oral GSH supplementation daily for a period of six months. Fasting and PP glucose, insulin, HbA1c, GSH, oxidized glutathione (GSSG), and 8-hydroxy-2-deoxy guanosine (8-OHdG) were measured upon recruitment and after three and six months of supplementation. Statistical significance and effect size were assessed longitudinally across all arms. Blood GSH increased (Cohen’s d = 1.01) and 8-OHdG decreased (Cohen’s d = −1.07) significantly within three months (p < 0.001) in diabetic individuals. A post hoc sub-group analysis showed that HbA1c (Cohen’s d = −0.41; p < 0.05) and fasting insulin levels (Cohen’s d = 0.56; p < 0.05) changed significantly in diabetic individuals above 55 years. GSH supplementation caused a significant increase in blood GSH and helped maintain the baseline HbA1c overall. These results suggest GSH supplementation is of considerable benefit to patients above 55 years, not only supporting decreased glycated hemoglobin (HbA1c) and 8-OHdG but also increasing fasting insulin. The clinical implication of our study is that the oral administration of GSH potentially complements anti-diabetic therapy in achieving better glycemic targets, especially in the elderly population.

Prenatal exposure to heavy metals is known to be associated with adverse birth outcomes and oxidative stress biomarkers. In this study, we examined whether maternal free cortisol or 8-Hydroxy-2-Deoxyguanosine (8-OHdG) could mediate associations between maternal heavy metal exposure and birth outcomes. A total of 182 healthy pregnant women were recruited. Heavy metals (including Pb, Hg, and Cd), free-cortisol, and 8-OHdG were analyzed in urine at delivery. Birth outcomes including birth weight, length, Ponderal index, and head circumference were measured. To examine associations of maternal urinary heavy metals with biomarkers and birth outcomes, generalized linear models were employed. Birth length was positively associated with Pb (β = 0.78, 95% CI: 0.09−1.46) and Hg (β = 0.84, 95% CI: 0.23−1.45) (both p < 0.05). The Ponderal index, a measure of a newborn’s leanness, was negatively associated with maternal urinary Pb (β = −0.23, 95% CI: −0.46−−0.07) and Hg (β = −0.26, 95% CI: −0.44−−0.08) (both p < 0.05). No association between maternal Cd and birth outcomes was observed. Most heavy metals showed positive associations with free cortisol and 8-OHdG. Free cortisol was identified as a mediator underlying the observed relationship between Hg and birth length or Ponderal index. This study observed adverse birth outcomes from maternal exposures to Pb and Hg. Increased free cortisol related to Hg exposure was suggested as a possible causal pathway from Hg exposure to birth outcomes such as the Ponderal index.

UNASSIGNED: Radon and its radioactive progenies are the most important source of ionizing radiation of natural origin, being classified as a Group 1 carcinogen. The aim of this study is to investigate the genotoxic effects of a wide range of indoor radon concentrations, as well as the kinetics of the process of repairing DNA-induced lesions by a challenging dose of gamma irradiation.
UNASSIGNED: Female subjects residing in the Băiţa-Ştei radon priority area were selected as the exposed group. The reference group was comprised of women from the same county (Bihor), but located in an area with an average indoor radon concentration typical of the county from which they were taken. Radon concentration values of 300 Bq/m3 and 148 Bq/m3, respectively, were chosen as a threshold in order to capture the impact of radon exposure between the groups. The alkaline comet assay was used in order to measure the DNA damage, as well as the repair kinetics at 2 and 24 h after 2 Gy challenging doses of gamma irradiation using peripheral blood lymphocytes. From the serum of the subjects, the oxidative damage by 8-hydroxydeoxyguanosine as well as the PARP induction was evaluated. The chromosomal aberrations were evaluated using the Cytokinesis Block MicroNucleus Assay.
UNASSIGNED: A statistically significant increase was observed in terms of DNA-induced lesions assessed by comet assay for the exposed group compared to the reference group. A positive correlation was obtained between DNA damage and the annual effective dose, respectively with the radon progenies concentrations. A statistically significant difference was also observed for the frequency of the micronuclei between the exposed - reference groups. Significantly faster repair kinetics of DNA-induced lesions was recorded for the first 2 h after gamma irradiation in the reference group compared to the exposed group. Using the threshold of 300 Bq/m3 for radon concentration, faster kinetics of DNA damage repair for people exposed to low radon concentrations, compared to those exposed to higher concentrations for the second phase of DNA repair kinetics was observed.
UNASSIGNED: An increased radiosensitivity of lymphocytes, as well as slower repair kinetics, may be associated with exposure to higher indoor radon concentrations.