Urinary 8-OHdG Levels Research Articles

Urinary monohydroxylated polycyclic aromatic hydrocarbons in primiparas from Shenzhen, South China: Levels, risk factors, and oxidative stress

The main objectives of the present study were to investigate urinary monohydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) in 77 primiparas who live in Shenzhen, Guangdong Province, China, and their association with 8-hydroxy-2′-deoxyguanosine (8-OHdG) and human health risks. High detection frequencies of OH-PAHs demonstrated the wide occurrence of chemicals in the human exposure to PAHs. The urinary concentrations of Σ7OH-PAHs ranged from 1.37 to 45.5 ng/mL, and the median concentrations of 1-hydroxynaphthalene (1-OHN), 2-hydroxynaphthalene (2-OHN), 2-hydoxyfluorene (2-OHF), ΣOHPhe (the sum of 1-, 2+ 3-hydroxyphenanthrene), and 1-hydroxypyrene (1-OHP) were 3.00, 2.58, 0.31, 0.44, and 0.51 ng/mL, respectively. In the sum concentration of seven OH-PAHs, 1-OHN accounted for the largest proportion (43.7% of Σ7OH-PAHs), followed by 2-OHN (37.1%), 2-OHF (4.94%), 1-OHP (8.01%), 1-OHPhe (4.79%), and 2+3-OHPhe (1.46%). The present results showed that vehicle exhaust and petrochemical emission are the main sources of PAHs in primiparas in Shenzhen, and inhalation is the most important exposure route. The living conditions have a significant influence on human exposure to PAHs. The concentrations of 8-OHdG were positively correlated with OH-PAH concentrations in urine because evidence suggested that urinary 8-OHdG levels can be considered as a biomarker of oxidative DNA damage. Hazard quotient was used to assess the human health risks from exposure to single compound, and hazard index was used to assess the cumulative risks of the compounds, which demonstrated that the exposure risks from PAHs in primiparas were relatively low.

Workers' Lifestyles and Urinary 8-hydroxydeoxyguanosine as an Oxidative Stress Marker

Oxidative stress in biological components has become recognized as one of the causative factors of various diseases. In this study, we investigated the effects of worker lifestyle and fatigue on the levels of urinary 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative stress. Our results revealed that urinary 8-OHdG level was increased by alcohol intake and decreased by snack intake and adequate sleep time on the day before the survey. A decrease in urinary 8-OHdG level was also observed in parallel with a decrease in workload. Urinary 8-OHdG monitoring is expected to be useful for disease prevention in the future.

Short-term effects of ambient air pollution and outdoor temperature on biomarkers of myocardial damage, inflammation and oxidative stress in healthy adults.

The mechanisms whereby ambient air pollution and temperature changes promote cardiac events remain incompletely described. Seventy-three nonsmoking healthy adults (mean age 23.3, SD 5.4 years) were followed with up to four repeated visits across 15 months in Beijing in 2014-2016. Biomarkers relevant to myocardial damage (high-sensitivity cardiac troponin I [hs-cTnI]), inflammation (growth differentiation factor-15 [GDF-15]), and oxidative stress (8-hydroxy-2'-deoxyguanosine [8-OHdG]) were measured at each visit, while ambient air pollution and temperature were monitored throughout the study. Linear mixed-effects models coupled with distributed lag nonlinear models were used to assess the impacts of each exposure measure on study outcomes. During follow-up, average daily concentrations of fine particulate matter and outdoor temperature were 62.9 µg/m3 (8.1-331.0 µg/m3) and 10.1 °C (-6.5°C to 29.5°C). Serum hs-cTnI levels were detectable in 18.2% of blood samples, with 27.4% of individuals having ≥1 detectable values. Higher levels of ambient particulates and gaseous pollutants (per interquartile range) up to 14 days before clinical visits were associated with significant alterations in hs-cTnI levels of 22.9% (95% CI, 6.4, 39.4) to 154.7% (95% CI, 94.4, 215.1). These changes were accompanied by elevations of circulating GDF-15 and urinary 8-OHdG levels. Both low (5th percentile, -2.5 °C) and high (95th percentile, 24.8°C) outdoor temperatures, with breakpoint at ~13.0°C as the reference level, were also associated with elevations of hs-cTnI levels. Short-term exposure to ambient air pollution and temperature was associated with cardiac troponin, a biomarker of myocardial damage, along with increased inflammation and oxidative stress responses. These findings extend our understanding of the biological mechanisms linking pervasive environmental exposure to adverse cardiac events.

Effects of Heavy Metal Exposure on Shipyard Welders: A Cautionary Note for 8-Hydroxy-2'-Deoxyguanosine.

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.

Heavy metal exposure, oxidative stress and semen quality: Exploring associations and mediation effects in reproductive-aged men.

Heavy metal exposure induces oxidative stress, which is critical for adverse male reproductive health. To explore the mediating effect of oxidative stress on the relationship of heavy metal exposure with semen quality. Urinary levels of three oxidative stress markers, semen quality, and urinary arsenic, cadmium and lead were examined among 1020 men. Multivariate linear regression was applied to explore cross-sectional associations, and the role of oxidative stress as mediators was investigated. Quartiles of metals showed significant dose-dependent relationships with increasing levels of 8-hydroxy-2deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA). Significant or suggestive associations were also found between urinary 8-OHdG levels and the percentage of normal sperm morphology (ptrend<0.001), between urinary 8-isoPGF2α levels and total motility (ptrend=0.052), progressive motility (ptrend=0.050) respectively. The mediation analysis showed that about 14.59%, 18.06%, 15.35% or 16.49% of the association between arsenic/cadmium exposure and the decreased total motility/progressive motility was mediated by 8-isoPGF2α, respectively. In addition, about 16.47% of the relationship between lead exposure and the decreased percentage of normal sperm morphology was mediated by 8-OHdG. Our findings suggest that higher urinary arsenic, cadmium and lead levels were associated with increased oxidative stress markers, which also related with altered semen quality. 8-isoPGF2α and 8-OHdG might be the possible mediators of the associations between urinary heavy metals and total motility, progressive motility or the proportion of normal sperm morphology.

Synthesis, Characterization, Antimicrobial Activity, and Genotoxicity Assessment of Two Heterocyclic Compounds Containing 1,2,3-Selena- or 1,2,3-Thiadiazole Rings.

New 1,2,3-thiadiazole and 1,2,3-selenadiazole derivatives, (4-[4-((4-bromobenzyl)oxy)-phenyl]-1,2,3-thiadiazole (5a), 4-[4-((4-chlorobenzyl)oxy)-phenyl]-1,2,3-thiadiazole (5b)), (4-[4-((4-bromobenzyl)oxy)-phenyl]-1,2,3-selenadiazole (6a), and 4-[4-((4-chlorobenzyl)oxy)-phenyl]-1,2,3-selenadiazole (6b)), were prepared and screened in vitro for their antimicrobial activity against various pathogenic microbes. In addition, two compounds (5a and 6a) were examined for their in vivo genotoxicity using rats and an 8-hydroxy-2′-deoxyguanosine (8-OHdG) assay. Compounds 5a and 5b were found to be highly active against Gram-positive and Gram-negative bacteria. In addition, a significant inhibition of urinary 8-OHdG level (50.2%) was observed upon treatment of animals with 500 mg/kg body weight (b.w.) of compound 6a (p < 0.0001). However, compound 5a increased urinary 8-OHdG levels. The lethal dose (LD50) values for compounds 5a and 6a were determined by an up-and-down procedure (OECD 425; OECD 1998), which showed that these compounds are safe, since the LD50 was >5000 mg/kg b.w. Thus, the tested compounds might have the potential for use as antibiotics, since they have low genotoxicity and strong antimicrobial activity.

Effects of maternal exposure to neonicotinoid pesticide and oxidative stress on birth outcomes

TPS 742: Adverse birth outcomes 1, Exhibition Hall, Ground floor, August 27, 2019, 3:00 PM - 4:30 PM Neonicotinoid (NEO) is an environmental pollutant and few studies have been reported on biological monitoring and health effects. The study aims to explore the associations among NEO exposure, oxidative stress, and neonatal birth outcomes. A total 260 mother-infant pairs were selected in Taipei, Taiwan, during 2014-2016. Maternal urine samples were collected during the 3rd trimester of pregnancy, and the information of birth outcomes was retrieved from the medical records. We developed an isotope-dilution high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) method to simultaneously quantify seven neonics, including acetamiprid, clothianidin, dinotefuran, imidacloprid, thiacloprid, thiamethoxam and nitenpyram in urine. Urinary oxidative stress biomarkers (8-hydroxy-2’-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO2Gua)) and lipid peroxidation (8-iso-prostaglandin F2a (8-isoPF2a), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)) were analyzed by HPLC-MS/MS. All infants born to mothers with urinary 8-OHdG levels above the median exhibited a significantly shorter gestational duration. We anticipate this research will help to elucidate the mechanisms and the health effects by which NEO exposure affect and provide the finding to guide future policy for management and control of NEO.

Study of the Mechanism Underlying the Onset of Diabetic Xeroderma Focusing on an Aquaporin-3 in a Streptozotocin-Induced Diabetic Mouse Model.

Xeroderma is a frequent complication in diabetic patients. In this study, we investigated the mechanism underlying the onset of diabetic xeroderma, focusing on aquaporin-3 (AQP3), which plays an important role in water transport in the skin. Dermal water content in diabetic mice was significantly lower than that in control mice. The expression level of AQP3 in the skin was significantly lower in diabetic mice than in control mice. One week after streptozotocin (STZ) treatment, despite their increased blood glucose levels, mice showed no changes in the expression levels of AQP3, Bmal1, Clock, and D site-binding protein (Dbp) in the skin and 8-hydroxydeoxyguanosine (8-OHdG) in the urine. In contrast, two weeks after STZ treatment, mice showed increases in the blood glucose level, decreases in AQP3, Bmal1, Clock, and Dbp levels, and increases in the urinary levels of 8-OHdG. The results of this study suggest that skin AQP3 expression decreases in diabetes, which may limit water transport from the vessel side to the corneum side, causing dry skin. In addition, in diabetic mice, increased oxidative stress triggered decreases in the expression levels of Bmal1 and Clock in the skin, thereby inhibiting the transcription of Aqp3 by Dbp, which resulted in decreased AQP3 expression.

Effect of exposure to phthalates on association of polycyclic aromatic hydrocarbons with 8-hydroxy-2'-deoxyguanosine.

Although polycyclic aromatic hydrocarbons (PAHs) and phthalates separately related to oxidative DNA damage have been reported, the joint effect of them on oxidative DNA damage need to be evaluated. In this pilot study, 106 participants were recruited from the community-dwelling residents (n=1240) of Wuhan city, China. Each individual provided three continuous days of spot urine samples for measuring the urinary monohydroxylated PAHs (OH-PAHs), phthalates metabolites and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in the two seasons. Linear mixed effect model and Bayesian Kernel Machine Regression (BKMR) were used to analyze joint effect of urinary PAHs and phthalates metabolites on urinary 8-OHdG levels. We measured cellular and mitochondrial reactive oxygen species (ROS), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) levels as well as IL-6 and IL-8 secretions by the corresponding commercial kits in HepG2 cells treated with di (2-ethylhexyl) phthalate (DEHP, 62.5, 125.00, 250.00, 500.00 or 1000.00μM) alone, benzo[a]pyrene (BaP, 50.00μM) alone or both DEHP and BaP. Linear mixed effect model showed that each of urinary PAHs metabolite was positively associated with urinary 8-OHdG levels; urinary level of mono (2-ethylhexyl) phthalate or monoisononyl phthalate was positively associated with urinary 8-OHdG levels; BKMR model indicated that a positive association of eight OH-PAHs with urinary 8-OHdG levels, nine urinary phthalates metabolites enhanced the association. We found that DEHP at the indicated concentration plus 50.00μM BaP increased cellular and mitochondrial ROS levels, IL-6 and IL-8 secretions at 24 and 48h as well as MDA levels and GSH-Px activities at 48h, compared to the solvent control. Exposure to certain dose phthalates may attenuate the positive association of PAHs exposure with oxidative DNA damage in the body. DEHP at the certain concentrations enhanced BaP-induced mitochondrial ROS, pro-inflammatory response and the activation of the antioxidant defense system in HepG2 cells.

A multibiomarker approach to evaluate the effect of polyaromatic hydrocarbon exposure on oxidative and genotoxic damage in tandoor workers.

We conducted a cohort study of tandoor workers to evaluate the relationship between the biomarkers of oxidative and genotoxic damage and exposure to polyaromatic hydrocarbons. A series of oxidative and genotoxic damage biomarkers, including urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), malondialdehyde (MDA) content, and tail moment (TM) by comet assay, was studied. A total of 76 tandoor workers and 79 demographically matched healthy individuals as controls were included. Our results showed that the tandoor workers had significantly higher urinary levels of 1-hydroxypyrene, urinary 8-OHdG, MDA content, and TM compared with the control population. The concentration of all these biomarkers increased with age in the control population as well as tandoor workers. In tandoor workers, significant variation in MDA, 8-oxodG (8-oxo-2'-deoxyguanosine) and TM concentration was detected between smokers (5.08 ± 1.72 nmol/mL, 16.01 ± 4.94 ng/mg creatinine, and 5.87 ± 0.98 µm, respectively) and nonsmokers (3.84 ± 0.98 nmol/mL, 13.74 ± 3.60 ng/mg creatinine, and 5.32 ± 0.69 µm, respectively). A similar pattern was obtained for the control population. We did not obtain significant variations for alcoholics and tobacco chewers. A significant increase in all these three biomarkers was observed with the increase in the period of work exposure in tandoor workers. Multivariate regression analysis also revealed that urinary 8-oxodG, MDA, and TM were statistically significantly related to age and period of work exposure. Overall, the present study showed that the exposure to wood smoke in tandoor workers under occupational conditions led to increased DNA damage because of oxidative stress and genotoxicity. These biomarkers, therefore, are good indices to assess oxidative DNA damage in these workers exposed to occupational genotoxicants. It is also necessary to make preventive changes in work conditions and lifestyle, which will help these occupational workers to lead a healthy life.

Urinary and Genetic Biomonitoring of Polycyclic Aromatic Hydrocarbons in Egyptian Coke Oven Workers: Associations between Exposure, Effect, and Carcinogenic Risk Assessment.

Background: Coke oven workers are exposed to polycyclic aromatic hydrocarbons (PAHs) with possible genotoxicity and carcinogenicity. Metabolizing enzymes genes and DNA repair genes are suspected to be correlated with the level of DNA damage. They may contribute to variable individual sensitivity to DNA damage induced by PAHs exposure at workplace. Objective: To investigate the relationship between biomarkers of PAHs: 1-hydroxypyrene (1-OHP), DNA adducts, and 8-hydroxy-2-deoxyguanosine (8-OHdG) in coke oven workers, and to assess the role of cytochrome P2E1 (CYP2E1) gene expression and DNA repairing gene (XRCC1) polymorphism in detecting workers at risk. Methods: 85 exposed workers and 85 unexposed controls were enrolled into this study. Urinary 1-OHP, 8-OHdG, and BPDE-DNA adduct were measured. CYP2E1 gene expression and genotyping of XRCC1 399 Arg/Gln were evaluated by real-time PCR. Results: The median urinary 1-OHP levels (6.3 µmol/mol creatinine), urinary 8-OHdG (7.9 ng/mg creatinine), DNA adducts (6.7 ng/μg DNA) in the exposed group were significantly higher than those in the unexposed group. Carriers of the variant allele (Gln) of XRCC1 had the highest levels of 1-OHP, DNA adducts and 8-OHdG, and the lowest level of CYP2E1 gene expression. In exposed workers, significant positive correlations were found between 1-OHP level and each of the work duration, 8-OHdG, and DNA adducts levels. There was a significant negative correlation between 1-OHP level and CYP2E1 gene expression. Work duration and CYP2E1 gene expression were predictors of DNA adducts level; 1-OHP level and work duration were predictors of urinary 8-OHdG level. Conclusion: Workers with higher exposure to PAH were more prone to oxidative DNA damage and cancer development. DNA adducts level reflects the balance between their production by CYP2E1 and elimination by XRCC1 gene.

Determination of 3-Hydroxybenzo[a]pyrene Glucuronide/Sulfate Conjugates in Human Urine and Their Association with 8-Hydroxydeoxyguanosine.

While 3-hydroxybenzo[a]pyrene (3-OHBaP) is a preferable biomarker to assess human exposure to benzo[a]pyrene (BaP), a sensitive and simple method is lacking. In this study, a specific and sensitive method based on liquid chromatography coupled with electrospray tandem mass spectrometry (LC-ESI-MS/MS) was developed for direct analysis of 3-OHBaP glucuronide and sulfate conjugates in human urine samples without enzymatic hydrolysis. The limits of detection (LODs) were 0.06 ng L-1 for BaP-3-sulfate (BaP-3-S) and 0.16 ng L-1 for BaP-3-glucuronide (BaP-3-G), which showed high sensitivity. Both compounds showed excellent linearity (r2 > 0.99) in the range of 0.01-10 μg L-1 in the instrumental calibration. The absolute recoveries of the target analytes spiked in human urine for the entire analytical procedure were 68.3 ± 4.96% (mean ± SD) and 63.7 ± 5.47% for BaP-3-S and BaP-3-G, respectively. This method was applied to quantify BaP-3-G and BaP-3-S in 150 urine samples collected from healthy volunteers. The mean concentration of BaP-3-S was 0.67 ng g-1 creatinine (<LOD to 10.20 ng g-1 creatinine), about 10-fold lower than that of BaP-3-G (6.73 ng g-1 creatinine, < LOD to 52.64 ng g-1 creatinine). For comparison, we also detected the concentration of free 3-OHBaP in 15 randomly selected samples without enzymatic hydrolysis and found at least >98% of 3-OHBaP is excreted mainly in these two conjugated forms in human urine. A statistically significant positive association was observed between urinary 3-OHBaP conjugates and urinary 8-OHdG levels (p < 0.001) in the general population. This study developed a sensitive and simple method to determine urinary glucuronide/sulfate conjugated BaP metabolites and for the first time found that BaP exposure associated with 8-OHdG levels in the general population.

Evaluation of urinary 8-hydroxy-2-deoxyguanosine level in experimental Alzheimer's disease: Impact of carvacrol nanoparticles.

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, AlCl3 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 AlCl3 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 AlCl3 administration in treated rats. While the treatment with both approached succeeded to retract the negative impact of AlCl3; but the effect of carvacrol nanoemulsion was more notable than the essential oil. Carvacrol oil and carvacrol nanoemulsion were eminent to overturn AlCl3 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.

Urinary 8-hydroxydeoxyguanosine in relation to XRCC1 rs25487 G/A (Arg399Gln) and OGG1 rs1052133 C/G (Ser326Cys) DNA repair genes polymorphisms in patients with chronic hepatitis C and related hepatocellular carcinoma.

Background and aim: DNA repair represents a protective mechanism against cell injury and cancer. 8-hydroxy-deoxyguanosine (8-OHdG) is the main ROS-induced DNA mutation. The current study aimed to evaluate urinary 8-OHdG levels in patients with chronic hepatitis C virus (HCV) and its related hepatocellular (HCC) and correlate its level to XRCC1 rs25487 G/A and OGG1 rs1052133 C/G gene polymorphisms.Materials and methods: Urinary 8-OHdG assays were performed using HPLC technique, and XRCC1 rs25487 G/A and OGG1 rs1052133 C/G gene polymorphisms were analyzed by PCR using confronting two-pair primer method (PCR-CTPP) in 200 subjects allocated into 50 chronic HCV patients, 50 HCV-related HCC patients, and 100 controls.Results: There were significantly increased urinary 8-OHdG levels in HCV-related HCC and chronic HCV patients when compared with the controls (P<0.05 for all). Urinary 8-OHdG was associated with the tumor spread. Regarding, XRCC1 (Arg399Gln), AA (Gln/Gln) genotype and A-allele were more frequent in HCC and chronic HCV patients than in the controls (P<0.05). ORs (95%CI) using the dominant and the recessive genetic models were; 2.1 (1.1–4.1), P=0.032 and 1.9 (1–3.6), P=0.043 respectively. For OGG1 (Ser326Cys), GG (Cys/Cys) genotype and G-allele were increased significantly in chronic HCV and HCC patients compared to the controls (P<0.05). ORs (95%CI) under the dominant and the recessive genetic models were; 2.1 (1.1–4.1), P=0.032 and 1.9 (1–3.8), P=0.049 respectively. Additionally, XRCC1 (AA) and OGG1 (GG) genotypes had significantly increased urinary 8-OHdG levels among patients (P<0.05).Conclusions: XRCC1 (AA) and OGG1 (GG) could be considered as possible genotypic risk factors for HCV- related HCC development which were associated with significantly high urinary 8-hydroxy-deoxyguanosine levels, thus urinary 8-OHdG could be considered as non-invasive marker in follow-up chronic HCV progression into HCC.

Pleiotropic association of LIPC variants with lipid and urinary 8-hydroxy deoxyguanosine levels in a Taiwanese population

BackgroundHepatic lipase (HL, encoded by LIPC) is a glycoprotein primarily synthesized and secreted by hepatocytes. Previous studies had demonstrated that HL is crucial for reverse cholesterol transport and affects the metabolism, composition, and level of several lipoproteins. In current study, we investigated the association of LIPC (Lipase C, Hepatic Type) variants with circulating and urinary biomarker levels by using subgroup and mediation analyses.MethodsA total of 572 participants from Taiwan were genotyped for three LIPC single nucleotide polymorphisms (SNPs) by using TaqMan assay. Fasting levels of glucose, lipid profile, inflammation markers, urine creatinine and 8-hydroxy deoxyguanosine (8-OHdG) were measured. The chi-square test, 2-sample t test and Analysis of variance (ANOVA) were used to examine differences among variables and genotype frequencies.ResultsSNPs rs2043085 and rs1532085 were significantly associated with urinary 8-OHdG levels, whereas all three SNPs were more significantly associated with Triglycerides (TG) or HDL-cholesterol (HDL-C) levels after additional adjustment for HDL-C or TG levels, respectively. Subgroup analyses revealed that the association of the LIPC SNPs with the levels of serum TG, HDL-C, and urinary 8-OHdG were predominantly observed in the men but not in the women. Differential associations of the LIPC SNPs with various lipid levels were observed in participants with different adiposity statuses. Mediation analyses indicated that TG levels acted as a suppressor masking the association of the LIPC genotypes with HDL-C levels, particularly in the men (Sobel test, all P < 0.01).ConclusionOur data revealed that interaction and suppression effects mediated the pleiotropic association of the LIPC variants. The effects of the LIPC SNPs depended on sex, adiposity status, and TG levels. Thus, our findings can provide a method for identifying high-risk populations of cardiovascular diseases for clinical diagnosis.

Antioxidative Effects of Olive Polyphenols Compared to Vitamin E in Piglets Fed a Diet Rich in N-3 PUFA.

Simple SummaryOlive polyphenols exert many favorable properties, such as an antioxidative effect in humans, but are poorly studied in animals, especially in pigs. Therefore, we conducted a trial including olive leaf extract (OLE), which is rich in polyphenols, in pigs fed a linseed oil-enriched diet, which is a known cause of postprandial oxidative stress. OLE exerted some antioxidative effects in piglets fed a polyunsaturated fatty acid (PUFA)-rich diet without any negative effects, even when included in a higher concentration than that proposed for humans. Additionally, the inclusion of OLE did not compromise the zootechnical performance of the piglets as in the case of the dietary inclusion of olive leaves. Therefore, OLE could be used as an effective feed additive for beneficial effects on intestinal health and meat quality, among others.The aim of the current study was to assess the antioxidative effects of the dietary supplementation of olive leaf extract (OLE) in different concentrations compared to those of vitamin E in piglets under conditions of dietary n-3 PUFA-induced oxidative stress. Forty-eight castrated male piglets (10.6 ± 0.99 kg) were fed the following experimental diets: Cont− (low-fat diet, no supplement), Cont+ (high linseed oil diet, no supplement), Vit-E (as Cont+, 105 IU vitamin E/day), OLE-1 (as Cont+, 3.84 mg hydroxytyrosol equivalents (HEQs)/day), OLE-2 (as Cont+, 38.4 mg HEQ/day), and OLE-3 (as Cont+, 96 mg HEQ/day). After 21 days of feeding, the experimental diets, blood and urine samples were collected to assess the extent of the oxidative stress. Results indicated that diet OLE-1 lowered the activity of gamma-glutamyl transferase, protected DNA (measured as DNA tail %) and altered urinary 8-hydroxy-2’-deoxyguanosine (8-OHdG). Dietary vitamin E lowered the levels of urinary F2-isoprostanes, as well as of plasma malondialdehyde and γ-tocopherol, but raised the plasmatic α-tocopherol and altered the level of urinary 8-OHdG. In conclusion, only minor positive effects of dietary OLE on the oxidative stress parameters were observed. Additionally, OLE did not show concentration dependence.

Thiol-producing microbiota of the intestine modulate oxidative stress and inflammation in Chronic Kidney Disease

Background: Inflammation and oxidative stress are among the key contributing risk factors for cardiovascular disease (CVD) in chronic kidney disease (CKD). The human gut is the home for microbiota, of which some of the gram-negative gut bacteria are known to produce low-molecular-weight thiols including glutathione (GSH). GSH is used by mammals and eukaryotic cells as a substrate of glutathione peroxidase to eliminate reactive oxygen species. This study aims to investigate whether the presence of thiol-producing gut microbiota in CKD affects the level of oxidative stress and inflammation markers. Methods: This study examined the stool sample of 41 CKD patients at three hospitals in Surabaya, Indonesia to identify the gram-negative bacteria producing thiols. Based on Ellman's assay result, the study participants were grouped into patients with thiol-producing and non-thiol-producing gram-negative gut microbiota. The markers of inflammation, high sensitivity C-reactive protein (hs-CRP), total antioxidant capacity (TAC), and urinary oxidative stress marker 8-hydroxy-2' -deoxyguanosine (8-OHdG) were compared between the two groups. Results: The group with thiol-producing gut microbiota exhibited lower levels of plasma hs-CRP and urinary 8-OHdG compared to the group with non-thiol-producing gram-negative gut microbiota. In contrast, the group with thiol-producing gut microbiota has higher TAC compared to the group with non-thiol-producing gram-negative gut microbiota. Conclusion: This study emphasized that the phenotypical diversity regarding the ability to produce low-molecular-weight thiols might modulate inflammation and oxidative stress as CVD risk factors in CKD.

Changes in oxidative stress levels during two weeks of smoking cessation treatment and their association with nutritional characteristics in Japanese smokers.

Although several experimental studies have reported that oxidative stress levels decrease during smoking cessation, how they change among general smokers has yet to be completely elucidated. In the present study, a total of 23 smokers who underwent smoking cessation treatment were observed for two-week changes in their levels of 8-OHdG and 8-isoprostane. Physical and nutritional characteristics were measured at the initial patient visit, and casual urine samples were collected at the initial visit and at a follow-up visit two weeks later. Oxidative stress was measured by a high performance liquid chromatography electrochemical detector, and the two-week difference in the levels of oxidative stress was assessed according to demographic and nutrient factors. Neither the urinary level of 8-OHdG nor that of 8-isoprostane decreased, although the cotinine level was decreased at two weeks. A Two-way repeated ANOVA revealed a significant interaction for fat intake by time for the change in the 8-OHdG level (P=0.03) and significant interactions for α-tocopherol intake (P=0.03), iron intake, and carbohydrate intake (P=0.03), all of which were time-dependent for the change in the 8-isoprostane level. The 8-OHdG level decreased among smokers with a high fat intake and was increased with a low fat intake. The 8-isoprostane levels were decreased among smokers with a high carbohydrate intake and increased with a low carbohydrate intake, decreased with a low iron intake and increased with a high iron intake and decreased with a low α-tocopherol intake and increased with a high α-tocopherol intake. Although the present study failed to observe a decrease in oxidative stress levels during the two-week smoking cessation period, we hypothesize that the intake levels of specific nutrients when initiating smoking cessation treatment may predict any subsequent changes in the oxidative stress levels.

Health risk assessment for highway toll station workers exposed to PM2.5-bound heavy metals

Highway toll station workers exposed to vehicle emissions during their working time, could induce excessive reactive oxygen species (ROS) generation and lead to significant health effects. This study conducted a comprehensive exposure investigation of environmental pollutants and oxidative stress levels for highway toll station workers during March–May 2014 in Tianjin, China. PM2.5 exposure samples were collected by personal monitors during worker’ day-shift working time (9:00 a.m. - 5:00 p.m.), and particulate heavy metals were analyzed by ICP-MS. Urinary 8-OHdG concentrations were analyzed in pre- and post-work urine samples from selected subjects to reflect their oxidative stress (OS) level variation. Results showed that PM2.5 average exposure concentration was 230.73 ± 142.99 μg m−3. Pb, Zn and Cr were the most abundant elements of metals, accounting for over 70% of total particulate heavy metals. Values based on geoaccumulation index (Igeo) and enrichment factor (EF) analysis indicated that heavy metals including Pb, As, Cd, Cr, Ni, Cu, Zn were mainly derived from anthropogenic sources, presenting heavily pollution levels. Health assessment was conducted using integrated toxicity values and Monte Carlo simulation, and results indicated that exposure to PM2.5-bound heavy metals can trigger significant adverse non-carcinogenic and carcinogenic risk. Urinary 8-OHdG concentrations of participants elevated over 2 times after their day-shift working exposure, indicating that pollutants from vehicle emission could cause DNA damage for highway toll station workers. However, we did not find significant association between fine particle-bound heavy metals and urinary 8-OHdG levels. Much work should be conducted in the future study focusing on confounding factors.

Urinary levels of bisphenol A, F and S and markers of oxidative stress among healthy adult men: Variability and association analysis

BackgroundBisphenol F (BPF) and bisphenol S (BPS) are increasingly used as alternatives to endocrine disrupting chemical bisphenol A (BPA). Evidence from in vitro and animal studies demonstrates that BPA, BPF and BPS induce oxidative stress, a proposed mechanism that is relevant to various adverse health effects. Evaluation in humans is hampered by the potentially high within-subject variability of urinary measurements. ObjectiveTo evaluate the variability and associations of levels of BPA, BPS, BPF and 3 oxidative stress markers [i.e., 8-hydroxy-2-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)] in urine collected on multiple occasions over 3 months. MethodA total of 529 spot urine samples, including 88 first morning voids (FMVs) and 24-h specimens, were gathered from 11 adult men on days 0, 1, 2, 3, 4, 30, 60 and 90 and analyzed for BPA, BPF, BPS, 8-OHdG, 8-isoPGF2α and HNE-MA. Intraclass correlation coefficients (ICCs) were estimated to characterize the reproducibility of urinary bisphenols and oxidative stress markers, and linear mixed models were applied to assess the associations between markers of exposure and response. ResultsBPA and BPF were detected in ≥85% of the spot samples, while BPS in 13% of the samples. High degrees of within-subject variability were found for BPA, BPF, 8-OHdG, 8-isoPGF2α and HNE-MA in spot samples, FMVs and 24-h specimens (creatinine-corrected ICCs ≤ 0.37). The sensitivities were low-to-moderate (0.30–0.63) when using single spot samples or FMVs to predict high (>27th, or 36th percentile) 3-month average urinary levels of BPA, BPF, 8-OHdG, 8-isoPGF2α and HNE-MA. Collecting repeated specimens at different time points improved the accuracy of classification for markers of exposure and response. Elevated urinary BPA and BPF were associated with significantly higher levels of oxidative stress markers. ConclusionsRepeated urinary specimens are required to characterize bisphenol exposure levels and the oxidative stress status of individuals. Exposure to BPA and BPF may partly contribute to the elevated urinary levels of oxidative stress makers in adult men.