Urinary 8-OHdG Research Articles

Renoprotective effects of brown adipose tissue activation in diabetic mice.

BackgroundBrown adipose tissue (BAT) has been regarded as a potential target organ to combat obesity and related metabolic disorders. However, the effect of BAT activation on the development of diabetic kidney disease (DKD) remains unclear.MethodsDiabetic mice were induced by streptozotocin (STZ) combined with a high‐fat diet. To activate BAT, mice were administered 1 mg/kg per day, i.p., CL316,243, a β3‐adrenergic receptor agonist, for 4 weeks. Blood glucose, serum lipids, adipokines, 24‐hour urinary albumin, 8‐hydroxydeoxyguanosine (8‐OHdG), and circulating microRNA (miRNA) levels were analyzed, in addition to renal pathology. Histological changes (fibrosis, inflammation) were evaluated in the kidneys, as was the expression of oxidative stress‐related genes. Renal signaling pathways (fibroblast growth factor [Fgf]21/β‐klotho/FGF receptor 1c and AMP‐activated protein kinase[AMPK]/sirtuin 1 [Sirt1]/peroxisome proliferator‐activated receptor‐γ coactivator‐1α [Pgc1α]) were also evaluated.ResultsCompared with untreated STZ‐diabetic mice, CL316,243 treatment reduced blood glucose, albeit not significantly (20.58 ± 3.55 vs 23.60 ± 3.90 mM), and significantly decreased triglycerides and low‐density lipoprotein cholesterol and increased high‐density lipoprotein cholesterol. Simultaneously, BAT activation significantly decreased 24‐hour urinary albumin (34.21 ± 6.28 vs 70.46 ± 15.81 μg/24 h; P < 0.05) and 8‐OHdG, improved renal fibrosis, inflammation, and oxidative stress, and ameliorated renal morphological abnormalities. In addition to enhancing BAT activity, CL316,243 significantly increased serum adiponectin concentrations and renal Fgf21 sensitivity, and reactivated the renal AMPK/Sirt1/Pgc1α signaling pathway. Furthermore, CL316,243 treatment increased levels of some circulating miRNAs and downregulated expression of their target genes in the kidney.ConclusionsActivating BAT could improve kidney injury in diabetic mice via metabolic improvements and renal AMPK activation by beneficial adipokines and miRNAs.

Controlling parameters and characteristics of electrochemical biosensors for enhanced detection of 8-hydroxy-2\u2032-deoxyguanosine

This work discusses the parameters and characteristics required on the development of a scalable and reliable electrochemical sensor board for detecting 8-hydroxy-2′-deoxyguanosine (8-OHdG), an oxidative stress biomarker for diabetic nephropathy, cancer and Parkinson’s disease. We used Printed Circuit Board (PCB) technology to make a precise, low-cost bare sensor board. ZnO nanorods (NRs) and ZnO NRs: reduced graphene oxide (RGO) composites were used as a pathway for antibody immobilization on the working electrode (WE). The parameters and characteristics of the WE were controlled for enhancing the quality of the electrochemical sensor board. Thickness of the gold and the presence of ZnO NRs or their composite on the WE have influence on charge transference process and reproducibility of the sensor board. The amount of the antibody, and its incubation period are crucial to avoid saturation of the sites during immobilization step and reduce the cost of the sensor. Our ZnO NRs-based electrochemical sensor board showed high sensitivity and selectivity to 8-OHdG with detection capacity in the range of 0.001–5.00 ng.mL−1. The successful application of our immunosensor to detect 8-OHdG in urine was evidenced.

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.

Determination of seven urinary metabolites of benzene, toluene and xylene by ultra-high performance liquid chromatography-triple quadrupole mass spectrometry

Objective: To develop a method using ultra-high performance liquid chromatography-triple quadrupole mass spectrometry to determine the urinary metabolites of benzene, toluene and xylene. The selected metabolites are S-phenylmercapturic acid (S-PMA) , trans, trans-muconic acid (t, t-MA) , 8-hydroxy-2 deoxyguanosine (8-OHdG) , hippuric acid (HA) , 2-methylhippuric acid (2-MHA) , 3-methylhippuric acid (3-MHA) and 4-methylhippuric acid (4-MHA) . Methods: The urine sample was pretreated using methanol to precipitate the proteins. HSS T3 chromatographic column was used to separate the metabolites. The mass spectrometric acquisition was carried out using multiple reaction monitoring (MRM) after ionization with ESI source. External standard method was used for quantification. Results: All the standard curves showed good linear relation, and r of the seven metabolites was all above 0.999. The detection limits and quantitative limits of the seven metabolites were 0.01-500 ng/ml and 0.02-1 000 ng/ml (based on the actual dilution ratio) , respectively. The average spiked recoveries of four loadings ranged from 85.8% to 109.9%. The intra-day and inter-day precisions were 0.2%-4.5% and 0.6%-9.5%, respectively. The samples can be kept for at least 14 days at both 4 ℃ and -20 ℃. Conclusion: This method is simple, rapid and highly sensitive with low cost, and its accuracy, precision and stability can meet the daily test requirements. It can be applied for the determination of urinary S-PMA, t, t-MA, 8-OHdG, HA, 2-MHA, 3-MHA and 4-MHA for the occupational population exposed to benzene, toluene and xylene.

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.

The impact on T-regulatory cell related immune responses in rural women exposed to polycyclic aromatic hydrocarbons (PAHs) in household air pollution in Gansu, China: A pilot investigation

Previous studies found associations between impairments of immune functions and exposure to polycyclic aromatic hydrocarbons (PAHs) in ambient air pollution in the U. S. and China. However, the results remain inconclusive due to the limitations of these studies. In this study, we aimed to examine the direction and magnitude of immune changes related to PAH exposure from household air pollution among rural women living in Gansu, China. Healthy village women (n = 34) were recruited and enrolled in the study. Questionnaires were administered. Blood and urine samples were collected and analyzed during non-heating (September 2017, “summer”) and heating (January 2018, “winter”) seasons. Urinary 1-hydroxypyrene (1-OHP) was quantified as the biomarker of PAH exposure. To evaluate Treg cell related immune functions, we examined immunoglobulin E (IgE), percent of T-regulatory (Treg) cells, and gene expression of following: forkhead box transcription factor 3 (Foxp3), transforming growth factor-β (TGF-β), interleukin 10 (IL-10), and interleukin 35 (IL-35), composed of interleukin-12 alpha (IL-12α) and Epstein-Barr-virus-induced gene 3 (EBi3). Urinary 8-hydroxy-2-deoxyguanosine (8-OHdG) was measured to evaluate oxidative DNA damage. The results showed that the concentration of 1-OHP increased from 0.90 to 17.4 μmol mol-Cr −1 from summer to winter (p < 0.001). Meanwhile, average percent of Treg cells decreased from 5.01% to 1.15% (p < 0.001); IgE and mRNA expressions of Foxp3, TGF-β, IL-10, IL-12α and EBi3 all significantly decreased (p < 0.001); Urinary 8-OHdG increased from 12.7 to 30.3 ng mg-Cr −1 (p < 0.001). The changes in 8-OHdG, Foxp3 and TGF-β were significantly associated with the increase of 1-OHP. The results suggested that we observed a substantial increase of PAH exposure in winter, which was significantly associated with the repression on Treg cell function and oxidative DNA damage. Exposure to PAHs in household air pollution possibly induced immune impairments among rural women in northwest China.

Electrochemical analysis of 8-hydroxy-2′-deoxyguanosine with enhanced sensitivity based on exonuclease-mediated functional nucleic acid

In this work, an electrochemical method for sensitive analysis of 8-hydroxy-2′-deoxyguanosine, a key biomarker that is widely used to study oxidative injury-related diseases, is proposed based on exonuclease-mediated functional nucleic acid. In the design, exonuclease can not only distinguish the existence of target, but also suppress the background noise, thus the sensitivity can be enhanced. Moreover, DNAzyme designed in the functional nucleic acid can further improve the sensitivity of the analysis during signal generation process. Therefore, exonuclease-mediated functional nucleic acid may ensure high sensitivity of the assay. Further studies reveal that the detection of 8-hydroxy-2′-deoxyguanosine can be achieved with a linearity from 0.01 nM to 7.0 μM and a detection limit of 6.82 pM. The new method has also been successfully applied to the determination of 8-OHdG in urine with good results, indicating its great potential for practical use.

High Dose Vitamin E Attenuates Diabetic Nephropathy via Alleviation of Autophagic Stress.

It has been reported that autophagic stress, which is involved in many diseases, plays a key role in the development of diabetic nephropathy (DN). In this study, we investigated the effects of high dose vitamin E on renal tubular epithelial cells and autophagic stress-related mechanisms in diabetes condition. In diabetic rats, high dose vitamin E treatment significantly decreased the serum creatinine, urea nitrogen, urinary albumin and urinary protein, reduced the levels of LCN2, HAVCR1, LDH and 8-OHdG in urine, and attenuated the cellular apoptosis and interstitial fibrosis in renal cortex. In vitro, vitamin E could reduce the release of LCN2 and HAVCR1 and the protein levels of caspase 3 and TGF-β1, as well as improve the growth inhibition in cultured HK-2 cells after exposure to advanced glycation end products (AGEs). Also, LC3-II and SQSTM1-positive dots were significantly increased in the renal tubular epithelial cells of DN patients and diabetic rats, and in HK-2 cells after exposure to AGEs, which were markedly declined by vitamin E. In addition, we found that the autophagosome formation was not affected by AGEs, as assessed by the mRNA levels of LC3B, Beclin-1, and ATG7. However, AGEs blocked the lysosomal degradation of autophagosome, which was characterized by a decrease in the enzymatic activity of cathepsin B/cathepsin L and DQ-ovalbumin degradation in HK-2 cells, indicating that AGEs-induced accumulation of autophagic vacuoles was a sign of autophagic stress. Interestingly, vitamin E exerted a protective effect on lysosomes to reduce the autophagic stress. Taken together, we conclude that autophagic stress may play an important part in the progression of DN, and alleviation of autophagic stress though improvement of lysosomal function provides a promising novel approach for treating DN.

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.

OXIDATIVE STRESS AND GENOTOXICITY AMONG WORKERS EXPOSED TO COPPER IN A FACTORY FOR NON-FERROUS INDUSTRY IN EGYPT

Introduction: Exposure to high levels of copper at the workplace results in many adverse health effects with possible genotoxicity and carcinogenicity. Aim of work: To evaluate oxidative stress and detect the extent of DNA damage among workers at a copper processing factory. Materials and methods: The studied group is composed of 36 male workers from a copper processing factory and 34 male as a control group non-exposed to copper matched for age and socioeconomic status. Total antioxidant capacity was measured for all participants as an oxidative stress parameter, and urinary 8-OHdG was assayed by ELISA. Extent of DNA damage in leucocytes was also evaluated by comet assay as a biomarker of genotoxicity. Results: In the exposed workers, mean serum copper and urinary 8-OHdG were higher when compared to controls (155.1 ± 23 versus 77.9 ± 8.5 ug/dL and 9.7 ± 5 versus 4.1 ± 1.2 ng/mg creatinine, respectively; p<0.001 in each). T-AOC measured in exposed workers was significantly lower than that of the comparison group. There was significant DNA damage in leucocytes of exposed workers compared to the control group with mean comet tail length (9.5 ± 3.7 versus 5.7 ±1.4 mm; p < 0.001). T-AOC was negatively correlated with comet tail length; r=-0.64 and 8-OHdG showed positive correlation; r=0.71 (p < 0.001 for each). Linear regression models revealed that 8-OHdG is the significant predictor of DNA damage assayed by comet test whereas smoking, work duration and age had no significant effect on DNA damage. Conclusion: copper-exposed workers are at risk of oxidative stress with consequent DNA damage and potential genotoxic effect.

Chronic intermittent hypoxia-mediated renal sympathetic nerve activation in hypertension and cardiovascular disease

In sleep apnea syndrome (SAS), chronic intermittent hypoxia (CIH) is believed to activate the sympathetic nerve system, and is thus involved in cardiovascular diseases (CVD). However, since patients with SAS are often already obese, and have diabetes and/or hypertension (HT), the effects of CIH alone on sympathetic nerve activation and its impacts on CVD are largely unknown. We, therefore, examined the effects of CIH on sympathetic nerve activation in non-obese mice to determine whether renal sympathetic nerve denervation (RD) could ameliorate CIH-mediated cardiovascular effects. Male C57BL/6 (WT) mice were exposed to normal (FiO2 21%) or CIH (10% O2, 12 times/h, 8 h/day) conditions for 4 weeks with or without RD treatment. Increased urinary norepinephrine (NE), 8-OHdG, and angiotensinogen levels and elevated serum asymmetric dimethyl arginine levels were observed in the CIH model. Concomitant with these changes, blood pressure levels were significantly elevated by CIH treatment. However, these deleterious effects by CIH were completely blocked by RD treatment. The present study demonstrated that CIH-mediated renal sympathetic nerve activation is involved in increased systemic oxidative stress, endothelial dysfunction, and renin-angiotensin system activation, thereby contributing to the development of HT and CVD, thus could be an important therapeutic target in patients with SAS.

The Research of PAHs Exposure Level Test by Urinary Biomonitoring

Some workers had that exposure levels and health effects of polycyclic aromatic hydrocarbons (PAHs) analysed through personal urinary biomonitoring. Personal particulate samples were collected in highway workers’ day shift working time. The spot urine samples were collected on each participant. In these samples, PAHs suggested by US-EPA were measured, and in the urine samples oxidative stress biomarker was analysed. The measured mean occupational exposed concentration of PM2.5 was 230.73 μgm-3, and the mean p-PAHs exposed concentration was 319.90 ngm-3 for the selected workers. Urinary concentrations of 8-OHdG increased by times following an 8-h work shift in participants. Significant positive associations were found between post-work shift urinary 8-OHdG and p-PAH concentrations. It’s indicated that air exposures for PAHs originating from traffic emissions are important in increasing oxidative burdens in human body.

Central obesity transition increased urinary levels of 8-hydroxydeoxyguanosine in male adults: A 3-year follow up study

ObjectiveAssociation of oxidative DNA damage with gain in anthropometric indices has not been fully elucidated. MethodsIn this study, participants (n = 1151) were derived from the baseline visit of Wuhan residents in the Wuhan-Zhuhai Cohort Study. The participants finished the physical examinations at both baseline and 3-year follow up. Urinary levels of 8-hydroxydeoxyguanosine (8-OHdG) were measured by gradient-elution high performance liquid chromatography method and then calibrated by urinary creatinine (Cr) values. ResultsGeneralized linear models showed that after adjusted for confounding factors, baseline central obesity individuals with a ≥2.5% hip circumference (HC) loss or >5% HC gain had a 0.290 μmol/mol Cr (95% confidence interval (CI): 0.108, 0.472) or 0.553 μmol/mol Cr (95% CI: 0.273, 0.833) increase in urinary 8-OHdG levels compared with those with a −2.5%–2.5% HC gain (both P < 0.05). Moreover, compared with non-central obesity at both baseline and 3-year follow-up, we observed that central obese men at both baseline and 3-year follow-up had a 0.46 μmol/mol Cr (95% CI: 0.16, 0.75) increased in urinary 8-OHdG levels. ConclusionsHC gain showed dose-dependent associations with urinary 8-OHdG levels. Moreover, male central obesity at both baseline and 3-year follow-up had an increased risk for urinary 8-OHdG levels.

Pelvic venous congestion induces lower urinary tract dysfunction in rats.

Pelvic venous congestion (PC) is thought to be related to several diseases of the lower urinary tract (LUT). We examined the characteristics of the LUT in rats with PC. To create PC, female rats were anesthetized with isoflurane, and the bilateral common iliac veins and bilateral uterine veins were ligated. At 1-8 weeks after either ligation or sham surgery, we performed cystometry with or without administration of carbazochrome sodium sulfonate hydrate or propiverine hydrochloride, histologic examination of the bladder, blood flow imaging, assessment of locomotor activity, measurement of urinary 8-hydroxydeoxyguanosine (8-OHdG) and nitric oxide metabolites (NOx), and the Evans blue dye extravasation test. PC elevated frequency of urination after 2-6 weeks, and caused a decrease of spontaneous locomotor activity. In addition, there was a decrease of bladder blood flow, an increase of bladder vascular permeability, an increase of urinary 8-OHdG, a decrease of urinary NOx, and mild inflammatory changes of the bladder. In rats with PC, frequency of urination was normalized by administration of propiverine or carbazochrome. Rats with PC may be used as a model of PC associated with high frequency of urination, and this model may be useful when developing treatment for LUT symptoms associated with PC.

Comet Assay and Urinary 8-OHdG: A Marker of Oxidative Stress in Oral Cancer with Puducherry Population

Comet Assay and Urinary 8-OHdG: A Marker of Oxidative Stress in Oral Cancer with Puducherry Population

Oxidative stress and immune aberrancies in attention-deficit/hyperactivity disorder (ADHD): a case-control comparison.

The objective of this study is to compare oxidative stress and immune biomarkers between attention-deficit/hyperactivity disorder (ADHD) patients and controls without ADHD. A case-control comparison between 57 paediatric (6-12years) untreated ADHD patients from the Antwerp University Hospital and 69 controls without ADHD from random schools in Flanders, Belgium, was conducted. Erythrocyte glutathione (GSH) and plasma lipid-soluble antioxidants (retinol, α-tocopherol, γ-tocopherol, retinyl palmitate, β-carotene, and co-enzyme Q10) were determined by HPLC with electrochemical detection, plasma malondialdehyde (MDA) by HPLC with fluorescence detection, plasma cytokines (interleukin (IL)-1β, IL-5, IL-6, IL-8, IL-10, tumour necrosis factor (TNF) and interferon (INF)-γ) and immunoglobulins (IgE, IgG and IgM) by flow cytometry and urinary 8-hydroxy-2'deoxyguanosine (8-OHdG) levels by ELISA assay. Dietary habits were determined by a food frequency questionnaire. Plasma MDA levels were on average 0.031µM higher in patients than in controls (p < 0.05), and a trend for higher urinary 8-OHdG was observed. Erythrocyte GSH and plasma retinyl palmitate levels, as well as IgG and IgE levels, were higher in patients than in controls as well (on average 93.707µg/ml, 0.006µg/ml, 301.555µg/ml and 125.004µg/ml, resp., p < 0.05). Finally, a trend for lower plasma IL-5 levels was observed. After Bonferroni correction for multiple testing, the difference in GSH levels remained statistically significant (nominally significant for retinyl palmitate), while significance was lost for MDA, IgG and IgE levels. Dietary habits do not appear to cause the observed differences. These results point at the potential involvement of slight oxidative stress and immune disturbances in ADHD.

Effect of linagliptin on oxidative stress markers in patients with type 2 diabetes: a pilot study.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are commonly used for the treatment of type 2 diabetes and have been previously shown to prevent diabetic renal injury via various mechanisms, including the attenuation of oxidative stress. Therefore, we hypothesized that linagliptin, a DPP-4 inhibitor, attenuates oxidized stress and diabetic renal injury. In total, 30 patients with type 2 diabetes who were undergoing treatment with linagliptin (5mg) during the 3-month study period were enrolled. Oxidative stress markers [serum malondialdehyde-modified LDL (MDA-LDL) and urinary 8-hydroxydeoxyguanosine (8-OHdG)], an inflammatory marker (high-sensitive CRP), urinary albumin excretion, estimated GFR, and a urinary tubulointerstitial injury marker [urinary liver-type fatty acid-binding protein (L-FABP)] were evaluated at baseline and after 3months of treatment. Following linagliptin treatment, serum MDA-LDL, serum HbA1c, and urinary L-FABP levels significantly decreased, while urinary 8-OHdG tended to decrease. In contrast, 1,5-AG levels increased, and high-sensitive CRP and urinary albumin excretion remained unchanged. In this study, we demonstrated that linagliptin partially attenuated oxidative stress. We also demonstrated that linagliptin treatment reduced urinary L-FABP excretion, suggesting that renal tubule-interstitial injury may be attenuated by linagliptin (UMIN 000015308).

The Effects of Melatonin on the Relationship between Air Pollution Levels and Biomarkers of Oxidative Stress and Platelet Activation in Healthy Young Adults

Urinary free malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) as biomarkers of oxidative stress as well as soluble P-selectin as a biomarker of platelet activation have been associated with air pollution exposure. However, the results have not been consistent across studies. We hypothesize that this inconsistency might be due to modification of circulating melatonin, a free radical scavenger and a key factor in the DNA damage repair system, on MDA and 8-OHdG responses to reactive oxygen species induced by air pollution exposure. Melatonin also regulates PPAR&amp;#947;/FUNDC1/ mitophagy pathways, hence affecting P-selectin level. We conducted a longitudinal study involving 70 healthy young adults living on a hospital campus in Shanghai. Indoor and outdoor PM2.5, O3, and NO2 were monitored throughout the study and combined with time activity pattern to estimate personal air pollution exposure. The results show that a 10% increase of urinary 6-sulfatoxymelatonin (aMT6s, a major metabolite of melatonin and highly correlated with circulating melatonin) was associated with a significant increase in urinary 8-OHdG by 2.4% [95% CI: 1.4%, 3.4%] and a significant decrease in urinary free MDA and soluble P-selectin by -1.5% [-2.4%, -0.6%] and -1.0% [-1.9%, -0.1%], respectively. Compared to unadjusted models (specified in parenthesis), models with urinary aMT6s as an effect modifier showed that 10 µg/m3 in PM2.5 12h personal exposure was associated with a change in urinary 8-OHdG by 11.0% [-2.4%, 24.3%] (unadjusted: -3.8% [-7.4%, -0.2%]), a change in urinary free MDA by 14.0% [2.4%, 25.7%] (unadjusted: -0.3% [-3.4%, 2.8%]), and 10 µg/m3 increase in NO2 12h personal exposure was associated with a change in P-selectin by 5.4% [-10.2%, 21.0%] (unadjusted: -5.3% [-9.5%, -1.1%]). Similar mediation effects were also observed for O3. These findings support the role of melatonin as a mediator for oxidative stress and platelet activation introduced by air pollution exposure.

Urinary MDA and 8-OHdG Concentrations among Agricultural Workers in South Korea and Influence of Protective Measures

Pesticides increase the quality of agricultural products, however routine exposure to these chemicals can results in adverse chronic health effects. Oxidative stress biomarkers such as malondialdeh...