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Objective: Deleterious effects of pollutants and ultraviolet radiation on the skin can be attenuated using formulations containing antioxidants. However, these have disadvantages, including chemical instability, photodegradation, poor bioavailability or biological activity. Here, two commercial formulations were evaluated: one optimized to stabilize and deliver ascorbic acid (AA) at 15% and the other containing a glucoside form of AA, namely ascorbic acid 2-glucoside (AA2G), at 1.8% and at a physiological pH. We compared the skin delivery, antioxidative effects and chemical stability of AA2G with AA in their respective formulations., Methods: Skin delivery was measured using fresh viable human skin explants, and oxidative stress was measured using a human reconstructed epidermal (RHE) model according to levels of malondialdehyde (MDA), superoxide dismutase (SOD) and catalase., Results: Ascorbic acid 2-glucoside was completely metabolized to AA by the skin before entering the receptor compartment. The skin contained parent and AA, indicating a reserve of AA2G was present for further metabolism. For AA2G and AA, maximum flux of AA-equivalents was at 12 h, with continued absorption over 24 h. The absolute amount in µg was higher in the skin after application of AA than after application of AA2G. This may suggest a greater antioxidative effect; however, according to all three measurements of oxidative stress, the protective effect of AA and AA2G was similar. Unlike AA, AA2G was chemically stable under storage conditions., Conclusion: A lower concentration of AA2G is as effective as the active metabolite, AA, in terms of antioxidant effects. AA2G was chemically stable and can be applied at a lower concentration than AA, thus avoiding the need for an acidic formulation with a pH below 3.5., (© 2021 Society of Cosmetic Scientists and Societe Francaise de Cosmetologie.)

Introduction: Few studies have investigated the role of exposure to metals and metal mixtures on oxidative stress in the general population., Objectives: We evaluated the cross-sectional association of urinary metal and metal mixtures with urinary oxidative stress biomarkers, including oxidized to reduced glutathione ratio (GSSG/GSH), malondialdehyde (MDA), and 8‑oxo‑7,8‑dihydroguanine (8-oxo-dG), in a representative sample of a general population from Spain (Hortega Study)., Methods: Urine antimony (Sb), barium (Ba), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), molybdenum (Mo), vanadium (V) and zinc (Zn) were measured by ICPMS in 1440 Hortega Study participants., Results: The geometric mean ratios (GMRs) of GSSG/GSH comparing the 80th to the 20th percentiles of metal distributions were 1.15 (95% confidence intervals [95% CI]: 1.03-1.27) for Mo, 1.17 (1.05-1.31) for Ba, 1.23 (1.04-1.46) for Cr and 1.18 (1.00-1.40) for V. For MDA, the corresponding GMRs (95% CI) were 1.13 (1.03-1.24) for Zn and 1.12 (1.02-1.23) for Cd. In 8-oxo-dG models, the corresponding GMR (95% CI) were 1.12 (1.01-1.23) for Zn and 1.09 (0.99-1.20) for Cd. Cr for GSSG/GSH and Zn for MDA and 8-oxo-dG drove most of the observed associations. Principal component (PC) 1 (largely reflecting non-essential metals) was positively associated with GSSG/GSH. The association of PC2 (largely reflecting essential metals) was positive for GSSG/GSH but inverse for MDA., Conclusions: Urine Ba, Cd, Cr, Mo, V and Zn were positively associated with oxidative stress measures at metal exposure levels relevant for the general population. The potential health consequences of environmental, including nutritional, exposure to these metals warrants further investigation., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Distal symmetric peripheral polyneuropathy (DSPN) is a highly prevalent complication of diabetes. However, underlying pathophysiological mechanisms are multiple and not well understood. The aim of our study was to analyze the oxidative stress levels in circulating mononuclear cells by measuring the glutathione system, malondialdehyde and oxidized-LDL, in 60 type 2 diabetic patients from a well-characterized cohort of 196 type 2 diabetic patients. Using a nested case-control design, we studied 30 type 2 diabetic patients with distal symmetric polyneuropathy and 30 diabetic controls without this complication, according to the Neuropathy Disability Score. We have found that diabetic patients with distal symmetric polyneuropathy showed significantly lower values of reduced glutathione (GSH) and reduced glutathione/oxidized glutathione (GSH/GSSG) ratio. These data indicate an increased consumption of glutathione in mononuclear cells from patients with distal symmetric polyneuropathy. No significant differences were found in malondialdehyde or in oxidized-LDL levels comparing both groups. These data show an altered glutathione response in circulating monocytes from diabetic patients with distal symmetric polyneuropathy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The role of selenium exposure in preventing chronic disease is controversial, especially in selenium-repleted populations. At high concentrations, selenium exposure may increase oxidative stress. Studies evaluating the interaction of genetic variation in genes involved in oxidative stress pathways and selenium are scarce. We evaluated the cross-sectional association of plasma selenium concentrations with oxidative stress levels, measured as oxidized to reduced glutathione ratio (GSSG/GSH), malondialdehyde (MDA), and 8-oxo-7,8-dihydroguanine (8-oxo-dG) in urine, and the interacting role of genetic variation in oxidative stress candidate genes, in a representative sample of 1445 men and women aged 18-85 years from Spain. The geometric mean of plasma selenium levels in the study sample was 84.76 µg/L. In fully adjusted models the geometric mean ratios for oxidative stress biomarker levels comparing the highest to the lowest quintiles of plasma selenium levels were 0.61 (0.50-0.76) for GSSG/GSH, 0.89 (0.79-1.00) for MDA, and 1.06 (0.96-1.18) for 8-oxo-dG. We observed nonlinear dose-responses of selenium exposure and oxidative stress biomarkers, with plasma selenium concentrations above ~110 μg/L being positively associated with 8-oxo-dG, but inversely associated with GSSG/GSH and MDA. In addition, we identified potential risk genotypes associated with increased levels of oxidative stress markers with high selenium levels. Our findings support that high selenium levels increase oxidative stress in some biological processes. More studies are needed to disentangle the complexity of selenium biology and the relevance of potential gene-selenium interactions in relation to health outcomes in human populations., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Oxidative stress (OS) has been observed in conditions affecting the cardiovascular system. Familial hypercholesterolemia (FH) is associated with an increased risk of premature coronary heart disease. In the postprandial state, circulating lipids and lipoproteins can modulate OS status. Our aim was to study the response of lymphomonocyte OS status and reactive oxygen species by-products after an oral unsaturated fat load test (OFLT) in those with FH and to compare this response with that obtained in normolipidemic, normoglycemic subjects. We studied 12 patients with FH and 20 healthy controls. In both groups, lymphomonocyte, oxidized/reduced glutathione ratio, and malondialdehyde were determined at baseline and at 2, 4, 6, and 8 hours after an OFLT. Fasting urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine and isoprostane were measured using standard procedures. In both groups, oxidized/reduced glutathione ratio and malondialdehyde significantly decreased in the postprandial state after the OFLT. Both parameters were significantly higher in the FH group at baseline and during all the postprandial points, but the reduction from the baseline levels was significantly higher in the FH group than in the control group. Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine was significantly increased in the FH group compared with the healthy control group, indicating a higher fasting OS status. We conclude that subjects with FH exhibited OS levels that were higher than in controls before and after an OFLT, but the improvement in the OS status after the unsaturated fat load was significantly higher in subjects with FH., (Copyright © 2013. Published by Mosby, Inc.)

Familial hypercholesterolemia (FH) is a clinical condition with high risk for developing atherosclerosis. Increased oxidative stress (OS) and FH have been related to atherosclerosis, but no data are available on levels of OS and antioxidant enzyme activity in circulating mononuclear cells (CMCs) from FH patients. Circulating mononuclear cells are important mediators in atherosclerosis development, and chronically increased blood OS present in FH can induce modification in CMC activity. The objective of the study was to analyze the OS levels in CMCs from FH patients and controls. We have selected 30 nonrelated FH index patients and 30 normoglycemic and normocholesterolemic controls matched by age, sex, body mass index, abdominal circumference, and homeostasis model assessment index. Production of free radicals was analyzed by measurement of xanthine oxidase activity in plasma, reduced and oxidized glutathione (GSH and GSSG, respectively), and malonyldialdehyde in levels CMCs. Antioxidant status was analyzed by measuring antioxidant enzyme activity as superoxide dismutase, catalase, and glutathione peroxidase. We have found that FH patients showed significantly higher xanthine oxidase and malonyldialdehyde enzyme activities, as well as increased GSSG and lower GSH values resulting in a higher GSSG/GSH ratio. These data indicate a higher free radical production in plasma and increased OS levels in CMCs from patients than from controls. No significant differences were found in superoxide dismutase, catalase, and glutathione peroxidase activities between both groups. These data show an important alteration of OS regulation in FH and the absence of antioxidant response in CMCs mediated by some of the major antioxidant enzymes., (Copyright 2010 Elsevier Inc. All rights reserved.)

Oxidative stress is associated with atherosclerosis. Familial combined hyperlipidemia (FCH) is considered as a human model of primary dyslipidemia and atherosclerosis frequently associated with insulin resistance (IR), but there are few data on its possible relation to oxidative stress. The objective of this study was to evaluate oxidative stress status using different markers in subjects with FCH assessing its possible correlation with anthropometric parameters and IR. This was a cross-sectional study. A cohort of 40 FCH patients (20 with IR (HOMA>or=3.2) and 20 without IR (HOMA<3.2)), and 20 healthy volunteers were included, all of them non-diabetic, normotensive and non-smokers. We measured lipid profile, glucose and insulin levels in plasma, HOMA, and representative indicators of oxidative stress such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG), reduced glutathione (GSH), oxidized glutathione (GSSG) and GSSG/GSH ratio in mononuclear cells. All parameters were determined at basal conditions with standard methodology in the three groups. All FCH subjects showed an increased status of oxidative stress compared to the control group. When the impact of IR was investigated, significant differences between groups were observed in terms of increased levels of 8-oxo-dG, GSSG and GSSG/GSH ratio in FCH subjects with IR indicating higher levels of oxidative stress in these patients. Correlation studies showed that 8-oxo-dG and GSSG/GSH ratio are independently related to IR with odds ratio of 3.5 and 7.4, respectively. We conclude that FCH is related to oxidative stress, especially in the presence of IR.

The objective of the present study was to analyze the impact of metabolic syndrome (MS) and its individual components on oxidative stress (OX) and on the activity of antioxidant enzymes of patients with essential hypertension. One hundred and eighty-seven hypertensives, 127 (61.9%) of them having criteria for MS according to the International Diabetes Federation criteria and 30 healthy normotensive subjects were included. OX status was assessed by measuring glutathione oxidized/glutathione reduced and reactive oxygen species-induced byproducts of lipid peroxidation, malondialdehyde, and DNA damage, 8-oxo-dG genomic and mitochondrial. Antioxidant enzymatic activity of Cu/Zn extracellular-superoxide dismutase (SOD) and catalase (CAT) was measured in plasma and glutathione peroxidase 1 in hemolysed erythrocytes. In mononuclear cells, total-SOD activity, CAT and glutathione peroxidase 1, were assessed as well. The OX state in both blood and peripheral mononuclear cells observed in hypertensives were not enhanced by the addition of components of the so-called MS. Likewise, the reduction in the activity of antioxidant enzymes, both extracellular and cytoplasmic, was not affected by the presence of additional components of the MS. Neither the number of components nor the individual addition of each of them, low high-density lipoprotein, triglycerides, abdominal obesity or fasting glucose, further impact in the OX abnormalities observed in those with only hypertension in absence of other components. In conclusion, the present data indicates that contribution of MS components to the OX burden generated by high blood pressure is minimal.

We have used two tumor cell clones (B9 and G2), derived from the methylcholanthrene-induced murine fibrosarcoma GR9 and normal BALB/c3T3 fibroblasts, to study the ability of t-BOOH derived reactive oxygen radicals to induce oxidative stress, apoptosis and c-fos and c-jun mRNA transcription. These clones differ in terms of their major histocompatibility complex (MHC) (H-2) class I genes expression, their tumor induction and metastatic potential and their reduced glutathione (GSH) levels. Incubation of both cell clones in the presence of t-BOOH results in the increase of 8-oxo-2'-deoxyguanosine (8-oxo-dG) and malondialdehyde and the decrease of GSH. The xenobiotic also induces the transcription of c-fos and c-jun mRNAs in normal fibroblasts and in B9 cell clone but not in G2 cell clone. In addition, G2 cell clone is more resistant to apoptosis when compared with normal fibroblasts or B9 cell clone. Higher levels of GSH in G2 cell clone may be the reason of their lower transactivation response and apoptosis. Thus lowering GSH concentration may be convenient not only for the efficiency of chemotherapy but also to induce a rather fast and direct apoptosis mechanisms in tumor cells. Most commonly antioxidants tested, superoxide dismutase, catalase, GSH and thiourea, were effective in the inhibition of t-BOOH-induced c-fos and c-jun mRNA transcription in normal fibroblasts suggesting, as expected, that different oxygen species are involved in the observed effects induced by the xenobiotic.

Objective: To assess the relationship between microalbuminuria and oxidative stress in mononuclear peripherals cells in essential hypertension., Methods: A total of 123 hypertensive patients in absence of antihypertensive treatment were included. A 24-h ambulatory blood pressure (BP) monitoring was performed using a Spacelabs 90207 monitor, and microalbuminuria was measured in 24-h urine collections. Oxidized/reduced glutathione ratio and the content of malondialdehide and damaged base 8-oxo-2'-deoxyguanosine in genomic and mitochondrial DNA were measured in peripheral mononuclear cells., Results: In the 29 (24%) microalbuminuric subjects, the amount of reduced glutathione was significantly lower and the ratio oxidized/reduced glutathione was significantly higher than in the normoalbuminuric subjects. In contrast, the simultaneous measurement of the levels of malondialdehide and 8-oxo-2'-deoxyguanosine from both genomic and mitochondrial DNA oxidation did not achieve statistical significance between the two groups. Subjects with the highest oxidized/reduced glutathione ratio tertile showed the highest urinary albumin excretion (UAE) (P = 0.04 for trend). In a stepwise multiple regression analysis, oxidized/reduced glutathione ratio was the main significant determinant of UAE accounting for the 9% of the variance when 24-h mean BP, age, sex, body mass index, glucose and total cholesterol were included in the model., Conclusions: Oxidative stress seems to be a determinant of UAE independent of BP levels even in hypertensive subjects.

Purpose: Our aim was to evaluate the postprandial effect of an oral fat load test (OFLT) rich in unsaturated fatty acids on gene expression profile in peripheral blood mononuclear cells (PBMC) from subjects with abdominal obesity as an insulin resistance model and controls. Methods: A total of 20 controls and 20 abdominal obese patients were studied. Metabolic parameters and oxidative stress markers were measured with standardized protocols. The whole gene expression at fasting state and after the OFLT (0, 4 and 8 h) was analysed using human HT-12-v4 expression beadchips, from Illumina. Results: We found a significant decrease in plasma glucose, insulin and oxidative stress markers in abdominal obese patients and controls. We found beneficial metabolic postprandial gene expression in three genes: FKBP5, DDIT4 and DHRS9. Following an OFLT, the postprandial mRNA expression of FKBP5, and DDIT4 was downregulated while that of DHRS9 was overexpressed, both in nondiabetic normolipidemic subjects and in insulin-resistant subjects with abdominal obesity. Conclusions: Our results suggest that an OFLT rich in unsaturated fatty acids downregulates the expression of FKBP5, coding for the glucocorticoid receptor pathway, and that of DDIT4, involved in the oxidative stress response. These changes could favourably influence the insulin resistance and oxidative stress status in the postprandial state. [ABSTRACT FROM AUTHOR]

Background: Abdominal obesity (AO) is a common modifiable risk factor for certain non-communicable diseases associated with enhanced oxidative stress (OS). The objective of this work was to investigate whether the interaction between antioxidant vitamin intake and OS-related polymorphisms modulates gene-associated anthropometry in a Spanish population. Methods: A total of 246 subjects with AO, and 492 age and gender matched non-AO subjects were included in the study. Anthropometric, biochemical, and OS parameters, and antioxidant dietary intake data were assessed using validated procedures. DNA from white blood cells was isolated and the genotype of seven polymorphisms from genes involved in OS (pro-oxidant and antioxidant) were analyzed using the SNPlex system. The effects of the c.-793T > C polymorphism on promoter activity and thus thioredoxin (TXN) activity were examined using reporter assays. Results: The AO group had higher 8-Oxo-2'-deoxyguanosine levels and took in less vitamin A and vitamin E compared to the non-AO group. Logistic regression analysis revealed that the rs2301241 polymorphism in TXN and rs740603 in catechol-O-methyltransferase (COMT) were associated with waist circumference (WC) and AO. Moreover, these polymorphisms were more strongly associated with variations in WC in subjects with low vitamin E intakes. A promoter assay revealed that the T to C conversion at c.-793 (rs2301241) induced a more than two fold increase in reporter gene expression. Conclusions: WC is associated both with dietary vitamin E intake and genetic variants of TXN and COMT suggesting that existence of a complex nutrigenetic pathway that involves regulation of AO. [ABSTRACT FROM AUTHOR]

Oxidative stress (OS) is a relevant intermediate mechanism involved in Type 2 Diabetes Mellitus (T2D) development. To date, the interaction between OS parameters and variations in genes related to T2D has not been analyzed. To study the genetic interaction of genes potentially related to OS levels (redox homeostasis, renin-angiotensin-aldosterone system, endoplasmic stress response, dyslipidemia, obesity and metal transport) and OS and T2D risk in a general population from Spain (the Hortega Study) in relation to the risk of suffering from T2D. One thousand five hundred and two adults from the University Hospital Rio Hortega area were studied and 900 single nucleotide polymorphisms (SNPs) from 272 candidate genes were analyzed. There were no differences in OS levels between cases and controls. Some polymorphisms were associated with T2D and with OS levels. Significant interactions were observed between OS levels and two polymorphisms in relation to T2D presence: rs196904 (ERN1 gene) and rs2410718 (COX7C gene); and between OS levels and haplotypes of the genes: SP2 , HFF1A , ILI8R1 , EIF2AK2 , TXNRD2 , PPARA , NDUFS2 and ERN1. Our results indicate that genetic variations of the studied genes are associated with OS levels and that their interaction with OS parameters may contribute to the risk of developing T2D in the Spanish general population. These data support the importance of analyzing the influence of OS levels and their interaction with genetic variations in order to establish their real impact in T2D risk. Further studies are required to identify the real relevance of interactions between genetic variations and OS levels and the mechanisms involved in them. [Display omitted] • Oxidative stress (OS) is an intermediate mechanism involved in Type 2 Diabetes Mellitus (T2D) development. • Hyperglycemia contribute to increased reactive oxygen species (ROS) generation and ROS can lead to insulin resistance. • Many genetic systems have been related to OS and T2D development • Studied SNPs and haplotypes are associated with OS. Their interaction with OS contribute to T2D in spanish population. [ABSTRACT FROM AUTHOR]

Background The interaction of cadmium with genes involved in oxidative stress, cadmium metabolism and transport pathways on albuminuria can provide biological insight on the relationship between cadmium and albuminuria at low exposure levels. Objectives We tested the hypothesis that specific genotypes in candidate genes may confer increased susceptibility to cadmium exposure. Methods Cadmium exposure was estimated by inductively coupled plasma mass spectrometry (ICPMS) in urine from 1397 men and women aged 18–85 years participating in the Hortega Study, a representative sample of a general population from Spain. Urine albumin was measured by automated nephelometric immunochemistry. Abnormal albuminuria was defined as urine albumin greater than or equal to 30 mg/g. Results The weighted prevalence of abnormal albuminuria was 6.3%. The median level of urine cadmium was 0.39 (IQR, 0.23–0.65) μg/g creatinine. Multivariable-adjusted geometric mean ratios of albuminuria comparing the two highest to the lowest tertile of urine cadmium were 1.62 (95% CI, 1.43–1.84) and 2.94 (95% CI, 2.58–3.35), respectively. The corresponding odds ratios of abnormal albuminuria were 1.58 (0.83, 3.02) and 4.54 (2.58, 8.00). The association between urine cadmium and albuminuria was observed across all participant subgroups evaluated including participants without hypertension, diabetes or chronic kidney disease. We observed Bonferroni-corrected statistically significant interactions between urine cadmium levels and polymorphisms in gene SLC30A7 and RAC1. Conclusions Increasing urine cadmium concentrations were cross-sectionally associated with increased albuminuria in a representative sample of a general population from Spain. Genetic variation in oxidative stress and cadmium metabolism and transport genes may confer differential susceptibility to potential cadmium effects. [ABSTRACT FROM AUTHOR]