Urinary 8-OHdG Research Articles

Association of oxidative stress with erectile dysfunction in community-dwelling men and men on dialysis

Objectives To investigate the association between oxidative stress and erectile dysfunction (ED) in community-dwelling men and men on dialysis. Methods This cross-sectional study included 398 community-dwelling men and 42 men on dialysis. Oxidative stress was assessed using 8-hydroxy-2'-deoxyguanosine (8-OHdG). Univariable and multivariable logistic regression analyses were performed to evaluate the association between oxidative stress and ED. Results Spearman’s rank correlation test showed no significant correlation between urine 8-OHdG levels and the 5-Item International Index of Erectile Function scores in community-dwelling men (ρ = −0.005, p = 0.917) and between plasma 8-OHdG levels and the Sexual Health Inventory for Men scores in men on dialysis (ρ = 0.166, p = 0.295). In community-dwelling men, univariable and multivariable analyses revealed that urine 8-OHdG level was not significantly associated with ED (odds ratio [OR]: 1.005, 95% confidence interval [CI]: 0.884–1.144, p = 0.934; OR: 0.930, 95% CI: 0.798–1.084, p = 0.353; respectively). In men on dialysis, univariable analyses revealed that plasma 8-OHdG level was not significantly associated with severe ED (OR: 0.967, 95% CI: 0.876–1.066, p = 0.498). Conclusions Oxidative stress was not significantly associated with ED prevalence and severity in community-dwelling men and men on dialysis.

Clinical significance of dynamics between oxidative stress levels during mechanical lung ventilation in premature infants with persistent pulmonary hypertension

The aim of this study was to determine the clinical significance of the levels and dynamics of the urinary 8-hydroxy-2-deoxyguanosine, degree of pulmonary hypertension on choosing the duration and form of respiratory support in premature infants with respiratory distress syndrome in combination with perinatal asphyxia.
 Materials and methods. The levels of the urinary 8-hydroxy-2-deoxyguanosine (8-OHdG), ng/ml were determined by enzyme immunoassay (ELISA) method and the degree of pulmonary hypertension (PH) - by echocardiography in 60 premature new-borns at 26-32 weeks of gestation on the 1st and the 3rd–5th days of life. A comparative analysis of indicators was carried out in 2 groups: I – 32 children with respiratory distress syndrome (RDS); II – 28 children with RDS combined with perinatal asphyxia. All infants received a respiratory support, depending on the clinical condition, blood gas analyses, and the chest X-ray.
 Results. The level and dynamics of the urinary 8-OHdG correlated to degree of PH, form, and duration of respiratory support. Children of the group II on the 1st day of life had echocardiogram indicators of mild PH and indicators of the urinary 8-OHdG 2.27±0.39 ng/ml; by 3rd–5th days of life – level of the urinary 8-OHdG increased to 4.10±0.42 ng/ml and the level of PH – to moderate, required 76.2 % longer respiratory support compared to children of the group I.
 Conclusions. Prematurely born infants with RDS in combination with perinatal asphyxia have a higher oxidative stress (OS) levels and more significant pulmonary hypertension, which requires a longer respiratory support by 76.2 % and more often use of high frequency oscillatory ventilation (HFOV) by 9.3 %

Performance of urinary biomarkers in differentiating dysfunctional voiding in women with overactive bladder syndrome: a prospective pilot study.

Dysfunctional voiding (DV) in women is a common disorder that causes bladder outlet obstruction (BOO) and may aggravate overactive bladder (OAB) symptoms. The diagnosis of DV relies on clinical alertness and videourodynamic study (VUDS). In this pilot study, we aimed to explore the diagnostic potential of urinary biomarkers in women with DV. Women who visited our institute for the management of OAB were enrolled in this prospective study. Urine samples were collected before treatment and urinary proteins were quantified using enzyme-linked immunosorbent assay (ELISA) kits. Patients with DV and patients with normal tracings were included in the study and control group, respectively. The patients with DV were further divided into two subgroups: those with and those without detrusor overactivity (DO). VUDS parameters and urinary protein levels were compared between each subgroup. A total of 67 women were enrolled. There were 47 patients with VUDS-diagnosed DV and 20 patients in the control group. Urinary 8-OHdG level (32.65 vs. 15.59, p < 0.001) and urinary TNF-α level (1.43 vs. 0.83, p = 0.031) were significantly higher in the DV group, and urinary IL-2 level (0.29 vs. 0.83, p < 0.001) was significantly lower in the DV group. Among the DV patients, urinary PGE2 level was higher in the DO group (240.4 vs 149.6, p = 0.049). In women with DV, urinary 8-OHdG level is elevated compared to women with normal VUDS. Urinary PGE2 level is elevated in patients with DV and DO. These finding suggests increased reactive-oxidative stress response and detrusor hyperactivity in DV patients. Urinary biomarkers can serve as potential non-invasive diagnostic tools in women with OAB.

Sestrin2 remedies podocyte injury via orchestrating TSP-1/TGF-β1/Smad3 axis in diabetic kidney disease

Sestrin2 is identified as a stress-induced protein and could functionate in many aspects. In our study, we investigated the latent impact of Sestrin2 on podocyte injury and its molecular mechanism in vivo and in vitro in diabetic kidney disease (DKD). Sestrin2 was low-expressed in renal biopsies from individuals with DKD, the glomeruli from diabetic mice, and mouse podocytes exposed to high glucose (HG). Sestrin2 overexpression ameliorated HG-induced phenotypic alterations, apoptosis, and oxidative stress in conditionally immortalized mouse podocytes and modulated the activity of Thrombospondin-1 (TSP-1)/transforming growth factor (TGF-β1)/Smad3 pathway in podocytes. Moreover, TSP-1 inhibitor LSKL or TGF-β blocker Pirfenidone arrested podocyte injury induced by HG. Streptozotocin (STZ) was employed to render equivalent diabetes in B6-TgN (CMV-Sestrin2) (TgN) and wild-type (WT) control mice. Sestrin2 alleviated increased levels of 24‐h urinary protein, blood urea nitrogen, serum creatinine and triglyceride, and urine 8-OHdG in diabetic mice. Podocyte phenotypic alterations, increased expression of apoptosis-associated proteins and podocyte loss were observed in WT but not in diabetic TgN mice, as well as oxidative stress. Additionally, TSP-1/TGF-β1/Smad3 signaling pathway was also suppressed in glomeruli of diabetic TgN mice. Thus, Sestrin2 mitigates podocyte injury in DKD via orchestrating TSP-1/TGF-β1/Smad3 pathway, underlining Sestrin2 as a promising therapeutic target for DKD.

8- Hydroxy -deoxyguanosine (8-OHdG) urine as a biomarker of oxidative damage in early elderly hypertension

According to JNC VII, patients with hypertension are patients who clinically have systolic and diastolic blood pressure ≥140 mmHg and ≥90 mmHg, respectively. The aging processes in hypertension are stiffening of the blood vessels and decreasing arterial flexibility. The underlying pathomechanism is oxidative stress due to reactive oxygen species (ROS) elevation. 8-Hydroxy-Deoxyguanosine (8-OHdG) is an oxidized product of DNA repair as a kind of oxidative stress biomarker. This study aimed to analyze urinary 8-OHdG in hypertensive patients and healthy control aged 46-55 years old by involveing 80 participants. Questionnaires and medical records were collected to obtain relevant clinical data. The level of 8-OHdG is measured by the Enzyme-Linked Immunosorbent Assay (ELISA). The results showed that there is no difference in the average urinary level of urinary 8-OHdG of hypertensive patients (1.871 ± 0.689 ng/mL) with the healthy controls (1.743 ± 0.364 ng/mL).

Risk of Pulmonary-Reproductive Dysfunctions, Inflammation and Oxidative DNA Damage in Exposure to Polycyclic Aromatic Hydrocarbon in Cigarette Smokers.

Background: Exposure to cigarette smoke has been associated with pulmonary and reproductive dysfunctions; inflammatory response, oxidative stress and oxidative DNA damage induced by polycyclic aromatic hydrocarbons (PAHs) present in cigarette smoke have been implicated in the pathogenesis of these disorders. The peak expiratory flow rate (PEFR), a biomarker of inflammation and oxidative DNA damage (8-hydroxy-2-deoxyguanosine (8-OHdG), tumor necrosis factor alpha (TNF-α)), reproductive hormones (testosterone (TST), luteinizing hormone (LH), follicle stimulating hormone (FSH)) cotinine and urinary PAH metabolite (1-hydroxypyrene (1-HOP)) were estimated in male active smokers. Methods: One hundred men aged 20-47 years, comprising 50 active male smokers and 50 non-smokers, were randomly recruited into this comparative cross-sectional study. The PEFR was measured using a peak flow meter, serum levels of cotinine, FSH, LH, TST, TNF-α, and urine 8-OHdG by enzyme-linked immunosorbent assay and 1-HOP by high-performance liquid chromatography. Data analysis was done using a t-test and correlation analysis at p≤0.05. Results: Smokers had significantly higher cotinine (49.73±31.76 versus 0.51±0.69 ng/ml, p≤0.001), 8-OHdG (16.34±12.10 versus 5.79±2.14 ng/ml, p≤0.001) and lower PEFR (309.20±56.05 versus 452.80±45.76 L/min, p≤0.001) and LH (5.75±2.06 versus 6.97±2.79 mIU/ml, p=0.015) compared to non-smokers. Duration of exposure to cigarette smoke correlated positively with cotinine (r=0.937, p≤0.001) and 1-HOP (r=0.813, p≤0.001) while cotinine correlated positively with 1-HOP (r=0.863, p≤0.001) only in smokers. Conclusion: Reduced lung function and luteinizing hormone and concurrent increase in oxidative DNA damage associated with exposure to cigarette smoke may suggest the involvement of PAH-induced DNA damage in the development of pulmonary and reproductive impairment in smokers.

8- Hydroxy-Deoxyguanosine (8-OhDG) urine as a biomarker of oxidative damage in late elderly diabetes mellitus

Diabetes Mellitus (DM) is a chronic metabolic disease characterized by high blood sugar levels that exceed normal limits. The DM pathomechanism involves oxidative stress, which has the potential to cause damage to cell components, including Deoxyribonucleic Acid (DNA). 8-hydroxy-deoxyguanosine (8-OhDG) is the most frequently detected oxidative DNA lesion. It is water-soluble and excreted in the urine. This study aimed to compare urine 8-OhDG levels in patients with controlled and uncontrolled blood sugar diabetes and healthy controls aged 56-65 years. Analytical descriptive research with a cross-sectional study design involved 80 participants determined with purposive sampling. The levels of 8-OhDG were measured using the Enzyme-Linked Immunosorbent Assay (ELISA) method. The results showed that urine 8-OhDG levels in DM patients (1.426±0.204ng/mL) were higher than in healthy controls (1.372±0.190ng/mL), although not statistically significant. Urine levels of 8-OhDG in DM patients aged 61-65 years (1.468±0.220ng/mL) were higher than in DM patients aged 56-60 years (1.394±0.190ng/mL), although not statistically significant. Urine levels of 8-Ohdg in controlled DM patient were lower (1.282±0.131 ng/mL) than in uncontrolled DM patient (1.569±0.159 ng/mL), were significantly different (p&lt;0.05). 8-OhDG produced by the body is the final product of oxidative DNA damage.

Concurrent alteration in inflammatory biomarker gene expression and oxidative stress: how aerobic training and vitamin D improve T2DM

BackgroundVitamin D (Vit D) supplementation and Aerobic Training (AT) exert several beneficial effects such as antioxidant and anti-inflammatory actions. The literature on the effects of AT and Vit D supplementation on the oxidative stress biomarkers and gene expression of inflammatory cytokines in patients with Type 2 Diabetes Mellitus (T2DM) is limited. The present study aimed to examine the effects of AT and Vit D supplementation on inflammation and oxidative stress signaling pathways in T2DM patients.Materials and methodsIn this single-blinded, randomized, placebo-controlled trial, 48 men with T2DM (aged 35–50 years with Body Mass Index (BMI) of 25–30 kg/m2) were randomly allocated into four groups: AT+Vit D (n = 10); AT + placebo (AT; n = 10); Vit D (n = 10), and Control + placebo (C; n = 10). The eight-week AT program was executed for 20–40 min/day, at 60–75% of heart rate maximum (HRmax), for 3 days/wks. The Vit D group received 50,000 IU of Vit D supplement capsules per week for 8 weeks. The serum levels of oxidative stress biomarkers and gene expression of inflammatory cytokines in the Peripheral Blood Mononuclear Cells (PBMCs) were evaluated using the RT-PCR method. To analyze the data, paired t-tests and one-way analysis of variance and Tukey’s post hoc test were used at the significance level of P < 0.05.ResultsThe result shows that serum 25-OH-Vit D, total nitrite, Total Glutathione (GSH), Total Antioxidant Capacity (TAC), Superoxide Dismutase (SOD), Catalase (CAT), and Glutathione Peroxidase (GPX) increased; and insulin, Fasting Blood Glucose (FBG), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), High Sensitivity C-Reactive Protein (hs-CRP), Malondialdehyde (MDA), glycated albumin, and Urinary 8-hydroxydeoxyguanine (8-OHdG) decreased significantly in all groups after 8 weeks, except for C. In addition, results of RT-PCR showed that AT+Vit D, Vit D, and AT significantly downregulated the gene expression of Tumor Necrosis Factor-Alpha (TNF-α), Interleukin-1 Beta (IL-1β), Mitogen-Activated Protein Kinases 1 (MAPK1), Nuclear Factor Kappa B (NF-κB) 1 (p50). It also upregulated Interleukin-4 (IL-4) gene expression, Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) in T2DM patients compared to the C.ConclusionAdditionally, the AT+Vit D group showed significantly lower insulin, FBG, HOMA-IR, hs-CRP, MDA, glycated albumin, urinary 8-OHdG, IL-1β, TNF-α, MAPK1, and NF-κB1 (p50) levels and significantly higher serum 25-OH-Vit D, total nitrite, GSH, TAC, CAT, SOD, GPX, IL-4, and PPAR-γ levels compared to the AT and Vit D groups. In T2DM patients, 8 weeks of AT+Vit D had a more significant impact on certain gene expressions related to inflammation and oxidative stress than Vit D or AT alone.

Red orange and lemon extract preserve from oxidative stress, DNA damage and inflammatory status in lambs

Oxidative stress causes several pathological conditions in farm animals by inducing a reduction in animal welfare and production with major economic losses for livestock. The standardised phytoextract obtained by red orange and lemon processing has antioxidant and anti-inflammatory activities. In this study we have investigated whether treating lambs for 40 days with red orange and lemon extract (RLE) was able to prevent the antioxidant and anti-inflammatory mechanisms, typically in newborn period. For this purpose, at the end of treatment, redox status was assessed in plasma using oxidative stress markers: malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) activities. Moreover, 8-hydroxy-2’-deoxyguanosine (8-OHdG) in urine was measured as a biomarker of DNA damage and finally, the markers of inflammatory status, interleukin (IL) 1β and 6, were measured in plasma by using an enzyme-linked immunosorbent assay (ELISA). Results showed that RLE-treated lambs improved antioxidant mechanisms as demonstrated by the increase in SOD, CAT and GPx activities and, furthermore, a significant reduction in oxidative stress-induced damage was demonstrated through MDA and 8-OHdG measurements. Moreover, RLE was also able to prevent the increase of pro-inflammatory cytokines concentration, such as IL- 1 β and IL 6. Results showed in the present paper demonstrate the potential beneficial effects of the RLE in lambs. HIGHLIGHTS Oxidative stress causes economic loss and welfare impairment in livestock. Several oxidative markers can be used to assess the redox status in plasma. The activity of some antioxidant enzymes increased in RLE treated lambs. A reduction of pro-inflammatory cytokines was recorded in RLE treated lambs.

La expresión de 8-hidroxi 2’-desoxiguanosina en el cáncer

The production of reactive oxygen species&#x0D; (ROS) takes place in all organisms. ROS regulate the cell&#x0D; cycle and other biological phenomena that make them&#x0D; essential for life. However, when there is a ROS excess&#x0D; and/or the antioxidant system is reduced, oxidative stress&#x0D; is induced. During this process, ROS can attack various&#x0D; biomolecules and generate oxidative damage. The hydroxyl&#x0D; radical is a highly reactive ROS that can react with guanine&#x0D; in deoxyribonucleic acid (DNA), generating the molecule&#x0D; 8-hydroxy-2’-deoxyguanosine (8-OHdG), a marker of&#x0D; oxidative damage to DNA. Some research have shown that&#x0D; cancer patients or mouse models of cancer have elevated&#x0D; levels of 8-OHdG in serum, urine, saliva, and tissues. This&#x0D; literature review summarizes the main findings of 8-OHdG&#x0D; in several types of cancer and shows the evidence for the&#x0D; potential use of 8-OHdG as a biomarker of oxidative DNA&#x0D; damage in cancer.

Diagnostic and prognostic value of urine biomarkers among women with dysfunctional voiding

The current study aimed to investigate the diagnostic and prognostic value of urine biomarkers among female patients with dysfunctional voiding (DV). Urine samples were collected from 43 female patients with DV and 25 controls. Oxidative stress biomarkers (8-hydroxy-2-deoxyguanosine [8-OHdG], 8-isoprostane, and total antioxidant capacity [TAC]) and inflammatory markers (interleukin-1 beta [IL-1β], IL-2, IL-6, IL-8, tumor necrosis factor alpha, nerve growth factor, and brain-derived neurotrophic factor) levels were analyzed. In total, 26 patients with DV received further treatment with biofeedback pelvic floor muscle exercise or external urethral sphincter botulinum toxin A injections. Patients with DV had significantly higher urine 8-OHdG, IL-1β, IL-8, and brain-derived neurotrophic factor levels than controls. Both urine 8-OHdG and IL-1β levels were positively correlated with clinical symptoms. Patients with DV who had successful treatment outcomes had significantly lower pretreatment urine 8-isoprostane and TAC levels than those with unsuccessful outcomes. The pretreatment urine TAC level was the only independent predictor of successful treatment outcomes (odds ratio: 0.995). Compared with controls, female patients with DV had distinct urine oxidative stress biomarker and inflammatory marker profiles, which also mapped their clinical characteristics and treatment outcomes. These urine analytes might have diagnostic and prognostic values among female patients with DV.

Do we have enough evidence to propose a urinary biomarker of bladder ischemia? A systematic review and meta-analysis.

Urinary bladder ischemia has been implicated in the pathogenesis of lower urinary tract symptoms (LUTS). However, research regarding urinary molecular markers for diagnosis and prognosis of pelvic ischemia is still premature, hindering further implementation in clinical practice. The aim of this study is to systematically appraise biomarkers associated with bladder ischemia detected in urine. We performed a systematic review of PubMed/Medline, Embase, Web of Science, and the Cochrane Library in October 2021 according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. A subsequent reference search of retrieved articles was also performed. The identified reports were reviewed according to Systematic Review Center for Laboratory Animal Experimentation's risk-of-bias tool for animal studies. Eight publications were selected for this analysis. The included reports used 8-hydroxy-2'-deoxyguanosine (8-OHdG) (in eight studies) as urinary marker of bladder ischemia. The pooled mean difference for urinary 8-OHdG levels between study and control groups was 13.73ng/mg creatinine (95% CI, 9.79-17.67; P< .001; I2 = 69%) for rat studies and 3.71 ng/mg creatinine (95% CI, 2.91-4.51; P< .001; I2 = 94%) for rabbit studies. The result remained statistically significant favoring the control group independent of the type of intervention used to achieve bladder ischemia. Regarding secondary outcomes, mean voided volume and micturition interval were significantly lower in the ischemia group. The lack of human randomized controlled trials is a major limitation. 8-OHdG is a urinary biomarker to be investigated in future studies for diagnosis and prognosis of LUTS in patients with vascular injury or bladder outlet obstruction.

Development of a colloidal gold based immunochromatographic strip for 8-OHdG detection

8-hydroxy-2'-deoxyguanosine (8-OHdG) is a sensitive and stable biomarker for evaluating DNA oxidative damage. A rapid and sensitive colloidal gold immunochromatographic strip was developed for 8-OHdG detection by a competitive method. The sample pad (glass cellulose film), bonding pad (glass cellulose film), nitrocellulose film and absorbent pad were pasted on the polyvinyl chloride (PVC) base plate to construct the test strip. Colloidal gold (AuNPs) was prepared by the reduction of chloroauric acid with sodium citrate. 8-OHdG antibody (Ab) was coated on the outer layer of AuNPs to form Ab@AuNPs as a probe. Bovine serum albumin (BSA) and 8-OHdG were conjugated with carbodiimide hydrochloride to prepare an artificial antigen, which was used as the coating antigen of detection line. Goat anti mouse polyclonal antibody IgG was used as the coating antibody of control line. The experimental parameters were optimized including the type of nitrocellulose membrane, the formula of loading solution, and the spraying amount of gold labeled antibody. The results showed that the appropriate nitrocellulose membrane was CN 95. The optimal loading solution included BSA (1%), Tween-20 (3%), sucrose (3%) and NaCl (0.9%). The optimal spraying amount of gold labeled antibody was 4 μL. 8-OHdG can be detected by the strip under visible light, and the level of 8-OHdG in urine can be preliminarily determined by comparing the color intensity of T line and C line. The 8-OHdG concentration in urine was further calculated by the gray value of T line and the threshold of detection was 2.55 μg/L. This colloidal gold immunochromatographic strip is simple, rapid and specific for detecting 8-OHdG in human urine to preliminarily evaluate the human status.

Prenatal neonicotinoid insecticides Exposure, oxidative Stress, and birth outcomes

BackgroundAn increasing number of studies have reported neonicotinoid insecticides (NEOs), the emerging alternatives to conventional insecticides, may increase oxidative stress and cause adverse health effects, but limited is known about the prenatal NEOs exposures and their impact on birth outcomes. ObjectivesWe investigated the levels of prenatal exposure to NEOs/metabolites, to assess their associations with birth outcomes, and investigate whether these associations could be mediated by oxidative stress using 8-OHdG as the biomarker. MethodsWe studied 296 mother-infant pairs recruited from Laizhou Wan Birth Cohort in 2010 – 2013. Two NEOs (IMI and ACE), three metabolites (6-CN, ND-ACE, and 2CTCA), and 8-OHdG were measured in maternal urine collected before delivery. Birth outcomes including birth weight, birth length, ponderal index (PI), head circumference, and gestational age, were acquired. We examined the associations between NEOs/metabolites and birth outcomes using multivariable linear regression. Mediation analysis was conducted to clarify the role of 8-OHdG on the association of NEOs/metabolites exposure and birth outcomes. ResultsHighest detection rate was observed for ACE (100.0%), followed by IMI (98.3%) and 6-CN (98.0%), suggesting the common exposure of pregnant women. The highest median concentration was observed for 6-CN with creatinine-adjusted median levels of 9.58 μg/g creatinine. A decrease in newborns’ head circumference was observed with a 10-fold increase in IMI (β = -1.83; 95% CI = -3.04, −0.62) and ACE (β = -2.27; 95% CI = -3.56, −0.98). An increase in newborns’ PI was observed with a 10-fold increase in IMI (β = 0.40; 95% CI = 0.03, 0.75). Maternal 8-OHdG demonstrated 38.5–65.5% mediating effects in the negative association of IMI, ACE, 2-CTCA with head circumference. These associations might differ between boys and girls. ConclusionsPregnant women were widely exposed to NEOs/metabolites in China. Results suggested the potential impacts of prenatal exposure to certain neonicotinoid insecticides on head circumference. Urinary 8-OHdG may partly mediate these associations.

Variations of Personal Exposure to Particulate Nitrated Phenols from Heating Energy Renovation in China: The First Assessment on Associated Toxicological Impacts with Particle Size Distributions

The clean heating renovation has been executed for improving particulate matter (PM) pollution in northern China since 2017. This study determined particle size distributions of nitrated phenols (NPs) in personal exposure samples and their associations with biomarkers in saliva and urine from homemakers in rural households of the Fenwei Plain, China. Remarkable reductions of 28.6-66.3% and 52.2-82.4% on PMs and total quantified NPs, respectively, were found with the substitutions of raw coal chunk and biomass by advanced clean coal. 4-Nitroguaiacol (4NG) showed the largest reductions of 81.2% among individual NP. In addition, the clean coal efficiently reduced interleukin-6 (IL-6) and 8-hydrox-2'-deoxyguanosine (8-OHdG) in the urine and saliva by 12-72%. Furthermore, significant positive correlations between urinary 8-OHdG with most of NPs in all particle sizes, urinary IL-6 with 4NG for particles with Dp > 2.5 μm and Dp = 0.25-1.0 μm and salivary IL-6 with 4-nitrocatechol and 4-methyl-5-nitrocatechol for particles with Dp > 2.5 μm, Dp = 0.5-1.0 μm, and Dp < 0.25 μm were observed but not for salivary 8-OHdG or PMs. The results provide scientific support for the clean energy reformation and demonstrate the strong particle size dependence between NPs and biomarkers.

S-Allylcysteine Ameliorates Aging Features via Regulating Mitochondrial Dynamics in Naturally Aged C57BL/6J Mice.

S-Allylcysteine (SAC) is the most abundant organosulfur molecule derived from aged garlic. The effects ofSAC on improving Aging in naturally aged C57BL/6J male mice and mitochondrial dynamics in Caenorhabditis elegans and its underlying mechanisms is evaluated. When mice have attained reproductive senescence at 60 weeks of age, SAC is supplemented to 0.05% and 0.2% into their normal diet for 12 weeks. The results show that SAC could significantly improve the level of hepatic optic atrophy 1 (OPA1) mRNA, which is a key factor for mitochondrial fusion, and consequently elevated the mitochondrial biogenesis-related proteins sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α), thus ameliorating oxidative stress, such as malondialdehyde (MDA) in the liver and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine. Among the biochemical markers of aging, SAC significantly reduces liver galactosidase β1 (GLB1) and senescence-associated β-galactosidase (SA-βgal), which are induced by replicative senescence. The mitochondria with green fluorescent protein (GFP)-tagged transgenic strain SJ4103 C. elegans is incubated with 5 or 50µM SAC, and SAC treated groups maintain the linear morphology of mitochondria. SAC regulates mitochondrial dynamics and ameliorated aging to a significant degree. This study also confirms that mitochondrial dynamics are a promising target for screening materials to combat aging and as a direction for anti-aging product development.

The role of oxidative stress markers in Indonesian chronic kidney disease patients: a cross sectional study

Background: Several aspects of chronic kidney disease (CKD) such as the incidence rate and mortality rate are concerning. Oxidative stress contributes to progression and mortality in patients with CKD; however, a specific correlation between several markers of oxidative stress and the estimated glomerular filtration rate (eGFR) and albumin-creatinine ratio (ACR) in the Indonesian population has not been sufficiently described yet. Methods: This study was an analytic observational study with a sample of 56 patients with CKD in Universitas Airlangga Hospital, Surabaya, Indonesia, from December 2019 – March 2020. The markers for oxidative stress investigated were urinary 8-hydroxy-2 deoxyguanosine (8-OHdG), serum symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA). The correlations between each variable of oxidative stress and CKD were analyzed using Pearson analysis. Results: There was a positive correlation between 8-OHdG and eGFR (p=0.00, r=0.51); however, there was a negative correlation between 8-OHdG and ACR (p=0.025, r=-0.30). SDMA and eGFR showed a negative correlation (p=0.00, r=-0.648), while SDMA and ACR showed a positive correlation (p=0.03, r=0.349). ADMA showed a negative correlation with eGFR (p=0.00, r=-0.476). There were significantly decreased 8-OHdG but increased ADMA and SDMA as the CKD stage progressed (p=0.001, p=0.00, and p = 0.00, respectively). Higher urine 8-OHdG was detected in patients without history of hemodialysis, whereas ADMA and SDMA showed higher value in patients with hemodialysis (p=0.00, p=0.00, and p=0.004, respectively), patients with history of diabetes mellitus (DM) had higher mean 8-OHdG (p 0.000) yet lower serum ADMA and SDMA (p=0.004 and p=0.003, respectively). Conclusions: In patients with CKD in Indonesia, the markers for oxidative stress 8-OHdG, SDMA, and ADMA are correlated with eGFR and ACR levels. There were also significant difference in 8-OHdG, SDMA, and ADMA levels among CKD stages, between dialysis vs non dialysis, and DM vs non DM patients.

Urinary 8-OHdG level is not affected by geography and trace elements in nail of residents of Addis Ababa: It is shaped by interactions between different social factors

The objective of this study was to evaluate the association between exposure to heavy metals and oxidative DNA damage among residents living in the potentially more polluted downstream (Akaki-Kality) area of Addis Ababa, in comparison to the upstream area (Gullele). For this, 8-hydroxy-2′-deoxyguanosine (8-OHdG) was used as a biomarker for oxidative DNA damage and heavy metals (Fe, Zn, Mn, Cu, Ni, Cr, Pb, As) as indicators of exposure. The concentrations of heavy metals in nails were determined using inductively coupled plasma optical emission spectroscopy (ICP-OES), and 8-OHdG in urine using Enzyme-Linked with Immunosorbent Assay (ELISA), from 95 residents of the two areas, upstream and downstream. The urinary 8-OHdG concentration was not significantly different (p = 0.05) between the two Sub-Cities, with mean of 18.50 ± 4.37 ng/mg Creatinine in Akaki-Kality and 17.30 ± 5.83 ng/mg Creatinine in Gullele. Also, there were no statistically significant (p = 0.05) difference among the different demographic groups according to gender, age, educational status, body mass index or habit of alcohol consumption. However, the interactions of sex with age, sex with alcohol consumption and alcohol consumption with education were found to affect the urinary 8-OHdG levels of residents of the two Sub-Cities. The mean concentrations (µg/g) of the elements were 488 and 1035 for Fe, 106 and 251 for Zn, 13.0 and 31.2 for Mn, 5.23 and 6.63 for Cu, 11.2 and 7.39 for Ni, 2.23 and 2.02 for Cr, 0.09 and 0.63 for Pb; and 0.16 and 0.25 for As, in nail samples from Akaki-Kality and Gullele, respectively. The determined concentrations of the heavy metals in nails were not significantly associated (p = 0.05) with the corresponding urinary levels of 8-OHdG. Hence, the observed 8-OHdG might have been caused by environmental exposure to toxic substances other than the analyzed heavy metals.

Combined effects of exposure to polycyclic aromatic hydrocarbons and metals on oxidative stress among healthy adults in Caofeidian, China

Exposure to polycyclic aromatic hydrocarbons (PAHs) and metals is associated with many adverse effects on human health, accompanied by oxidative stress. This study aimed to investigate the effects of co-exposure to PAHs and metals on oxidative stress in healthy adults. A preliminary longitudinal panel study was conducted between 2017 and 2018 in 45 healthy college students in Caofeidian, China. Six urinary monohydroxylated-PAHs (OH-PAHs), ten metals, 8-hydroxydeoxyguanosine (8-OHdG), and 8-iso-prostaglandin-F2α (8-iso-PGF2α) were measured. Linear mixed effects (LME) models and Bayesian kernel machine regression (BKMR) models were used to explore the associations of urinary OH-PAHs and metals with 8-OHdG and 8-iso-PGF2α. LME models showed that most urinary OH-PAHs and metals were positively associated with 8-OHdG and 8-iso-PGF2α. For example, a one-unit increase in the ln-transformed level of 1-hydroxypyrene (1-OHPyr) and vanadium (V) was associated with an increase of 143.8% (95% CI: 105.7 – 188.9%) and 105.8% (95% CI: 79.2–136.4%) in 8-OHdG; 8-iso-PGF2α increased by 118.9% (95% CI: 99.2–140.5%) and 83.9% (95% CI: 67.2–102.2%) with a one-unit increase in the ln-transformed level of 3-hydroxyphenanthrene (3-OHPhe) and aluminum (Al). BKMR models indicated the overall positive associations of the mixture of six OH-PAHs, ten metals, or six OH-PAHs and ten metals with 8-OHdG and 8-iso-PGF2α. Urinary 1-OHPyr and V were identified as the major contributors to the increased urinary 8-OHdG levels, while urinary 3-OHPhe and Al were the most vital contributors to the increased urinary 8-iso-PGF2α levels. The results revealed the longitudinal dose-response relationships of urinary OH-PAHs and metals with oxidative stress among healthy adults in Caofeidian; this finding serves as an evidence regarding the early health hazard caused by exposure to PAHs and metals and has implications for the environmental management of PAH and metal emissions in this area.

The effect of sodium-glucose cotransporter 2 inhibitor (tofogliflozin) on renal tubular damage in diabetic patients without albuminuria.

The sodium-glucose cotransporter 2 (SGLT2) inhibitors comprise a new class of glucose-lowering drugs for individuals with diabetes. Large-scale clinical trials indicated that SGLT2 inhibitors have both a cardiovascular-protective and renal-protective effects. A reduction in glomerular hyperfiltration and a decrease in albuminuria are suspected as the main causes of SGLT2 inhibitors' renoprotective effect. The effects of SGLT2 inhibitors on tubular damage in non-albuminuric diabetic patients are unclear. The SGLT2 inhibitor tofogliflozin (20mg, 1 × /day) was orally administered to 14 non-albuminuric diabetic patients. Serum and urine samples were collected at baseline (before) and after the start of tofogliflozin treatment. Hemoglobin A1c, hemoglobin, estimated glomerular filtration rate (eGFR), body weight, and blood pressure (BP) were analyzed as clinical parameters at baseline and 1, 3, and 6months later. Urinary neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl-β-D-glucosaminidase were measured as tubular damage markers and the urinary 8-hidroxydeoxyguanosine (8-OHdG) values were measured as an oxidative stress marker at baseline and at 1 and 3months. Compared to baseline, the patients' HbA1c values and body weights were significantly decreased post-tofogliflozin administration, and their eGFR values were decreased at 3months but recovered at 6months; the hemoglobin concentrations were significantly increased at 3 and 6months and the urinary NGAL level tended to be decreased at 3months. No significant changes in blood urea nitrogen, BP, NAG, urine sodium concentration, or urinary 8-OHdG values occurred. The effect of this SGLT2 inhibitor was not influenced by the use of an angiotensin receptor blocker or dipeptidyl-peptidase 4 inhibitor. For individuals with non-albuminuric diabetes, tofogliflozin has a good glucose-lowering effect and might have a tubular-protective effect.